| (i) | Interest shall be payable on any amounts owed by one Party to another Party which are not paid when due, at the Prime Rate plus 3% per annum, compounded monthly. The payment of interest shall not be deemed an alternative to the payment of amounts owing on the due dates, which payment shall be deemed to be in default, and if such default is not remedied within thirty (30) days of written notice thereof, UTIF may terminate this Agreement as provided in Section 6.2. |
ARTICLE 4
INTELLECTUAL PROPERTY
| 4.1 | Ownership |
All Intellectual Property Rights in all aspects and parts of the Technology and Improvements shall be exclusively owned by Owners, and/or David Lovejoy as the case may be, and nothing herein shall serve to, or should be construed to transfer any Intellectual Property Rights whatsoever in the Technology or Improvements.
| 4.2 | Know-how |
UTIF shall furnish a summary of the relevant Know-how to Licensee within a reasonable period of time following the execution of this Agreement.
| 4.3 | Patents and Patent Applications |
| (a) | UTIF, in the name of the Owners, or David Lovejoy as the case may be, as assignee, shall file, prosecute and maintain the Patents. Licensee, in consultation with UTIF, shall determine in which countries to pursue patent applications. In the event that Licensee elects not to reimburse UTIF for the costs associated with a patent application in accordance with Section 4.3 (c) hereunder or to continue prosecution in any country, UTIF may, at its sole discretion, file such patent or continue such prosecution in that country at its own expense. In such cases, any patents arising from such applications shall be excluded from the grant of rights under Section 2.1 herein and such country shall be deleted from the definition of Territory herein. |
| (b) | Licensee acknowledges that prior to the Effective Date of this Agreement, UTIF has incurred out-of-pocket expenses in relation to the filing and prosecution of the Patents. Licensee shall reimburse UTIF for such expenses (as evidenced by copies of invoices to be provided to Licensee) as follows: |
| (i) | Licensee shall pay UTIF ten thousand dollars ($10,000) within thirty (30) days following the Effective Date of this Agreement; and |
| (ii) | Licensee shall pay UTIF in consecutive installments of ten thousand dollars ($10,000) payable on a bi-monthly basis following the Effective Date of this Agreement until UTIF has been reimbursed in full. |
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| (c) | Subject to Section 4.3(a) herein, all out-of-pocket filing, prosecution and maintenance expenses in relation to the Patents incurred following the Effective Date of this Agreement shall be at Licensees sole expense. Without limiting the foregoing, Licensee shall pay UTIF any amounts anticipated to be payable or otherwise owing to any patent office in advance of when they would become due. |
| (d) | Subject to Sections 4.3(a) and 4.3(c) herein, the Parties hereto shall use reasonable commercial efforts to file patent applications in relation to STORM within two (2) years following the Effective Date of this Agreement. In the event that patent applications are not filed within this period, Licensee shall have the option to file, prosecute and maintain patent applications in relation to STORM subject to the following conditions: |
| (i) | David Lovejoy will be named as the assignee on all such patent applications; |
| (ii) | All out-of-pocket filing, prosecution and maintenance expenses will be at Licensees sole expense; and |
| (iii) | Licensee will undertake to keep UTIF reasonably advised of the progress of prosecution and of any actions Licensee proposes to take in connection with the prosecution or maintenance of such patent applications, and Licensee will diligently endeavor to provide UTIF with copies of correspondence and all actions issued by patent authorities. |
Provided that all of the conditions of this Section 4.3(d) have been satisfied, such patent applications in relation to STORM shall then be included in the definition of Patents for purposes of this Agreement and licensed to Licensee under the terms of license granted hereunder.
| (e) | UTIF undertakes to keep Licensee reasonably advised of the progress of prosecution and of any actions UTIF proposes to take or has taken in connection with the prosecution or maintenance of the Patents. UTIF shall diligently endeavor to provide Licensee with copies of correspondence and all actions issued by patent authorities and shall take into account any comments, remarks or suggestions Licensee may promptly provide to UTIF in writing at least ten (10) days prior to any due date established by UTIF for preparation of a response or amendment, and in all cases thirty (30) days prior to any patent office due date. |
| 4.4 | Improvements |
UTIF shall inform Licensee promptly of any Improvements. Within one hundred and eighty (180) days following the disclosure by UTIF of such Improvements, Licensee shall have the option to direct UTIF to file patent applications, in the name of the Owners, or David Lovejoy as the case may be, as assignee, in relation to the Improvements provided that Licensee agrees to pay all expenses associated with the filing and prosecution of such patent applications. Subject to any rights of Third Parties and to the provisions of Section 4.3(a) herein, such applications shall then be included in the definition of Patents for purposes of this Agreement and licensed to
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Licensee under the terms of license granted hereunder. If Licensee does not make its election within the one hundred and eighty (180) days or if Licensee elects for UTIF not to file patent applications for such Improvements, UTIF shall have the right to apply for patents at its own expense, and any patents resulting from such applications shall be excluded from the grant of rights under Section 2.1 herein. It is understood that Licensee shall not be obligated to undertake responsibility with respect to any such Improvements or developments unless it elects to do so.
| 4.5 | Infringement |
| (a) | Each Party shall notify the other Party promptly of any actual or threatened infringement, limitation or unauthorized use of any Technology by a Third Party of which such Party becomes aware. |
| (b) | Licensee shall have the right, at its own expense to bring any claim, action or proceeding on account of any such infringements, limitations or unauthorized use of the Technology. UTIF agrees that it shall cooperate with Licensee as Licensee may reasonably request in connection with any such claim, action or proceeding. Licensee agrees to reimburse UTIF for its reasonable expenses incurred in complying with any such request of Licensee. Any proceeds received by Licensee from such claim, action or proceedings shall be first applied to offset Licensees litigation expenses. Any remaining proceeds shall then be distributed according to Section 3.1(a) herein. |
| (c) | If Licensee does not undertake to bring any such claim, action or proceeding on account of any such infringements, limitations or unauthorized use within thirty (30) days following the receipt of notice of such infringement, limitation or unauthorized use, Licensee shall so notify UTIF and, at the expiry of such thirty (30) day period if the Licensee has not brought such claim, action or proceeding, UTIF may prosecute the same, at its expense. Licensee agrees that if UTIF brings such a claim, action or proceeding, Licensee shall cooperate with UTIF, at UTIFs expense, and UTIF shall be entitled to keep all the proceeds obtained from such claim, action or proceeding. |
| (d) | Licensee shall have the right, at its expense, to defend and settle for other than money damages any claim, action or proceeding that may be commenced against Licensee or UTIF alleging that any Licensed Product infringes any rights of others. UTIF may, at its option, participate in such claims, actions and proceedings through counselor as a party. Any settlement shall require the consent of UTIF. If Licensee does not defend or settle such claim, action or proceeding, it shall notify UTIF of its election within thirty (30) days (or such shorter time period as may be required in order that UTIF may have reasonably sufficient time to comply with any statutory obligations for instituting such defence) following the receipt of notice of same, and UTIF may defend same, at its expense. |
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| 4.6 | Confidentiality |
| (a) | All Confidential Information will remain the property of its owner or the Party that furnished it as the case may be. |
| (b) | Each Party agrees to maintain in confidence all Confidential Information disclosed with the same degree of care as it normally takes to preserve its own confidential information of similar grade, but in any event, no less than a reasonable degree of care. |
| (c) | Each Party may only disclose Confidential Information to persons with a need to know who shall be made aware of, and be required to observe and comply with the covenants and obligations contained herein, and the Confidential Information shall only be used to carry on or facilitate business as contemplated under this Agreement. |
| (d) | A Party may disclose Confidential Information pursuant to the requirements of a government agency or pursuant to a court order, provided that the Party shall take all reasonable steps, including, but not limited to the seeking of an appropriate protective order, to preserve the confidentiality of the Confidential Information provided. |
| (e) | If this Agreement is terminated for any reason, any Party in receipt of Confidential Information shall promptly deliver or destroy all Confidential Information of the disclosing Party without retaining copies thereof, except that the receiving Party may retain in the office of its legal counsel one (l) copy of written Confidential Information for record purposes only. |
| (f) | In the event that a Party becomes aware of, or perceives any threat that, any Confidential Information may be disclosed contrary to the provisions of this Section 4.6, or in the circumstances referred to in Subsection 4.6(c), such Party shall immediately provide written notice thereof to the other Party. |
ARTICLE 5
REPRESENTATIONS, WARRANTIES AND INDEMNITY
| 5.1 | Representations and Warranties of Parties |
The representations of Licensee and UTIF, one to the other are as follows:
| (a) | Licensee is a corporation duly organized, validly existing and in good standing, and it has the right and authority to enter this Agreement, and do all acts and things as required or contemplated to be done, observed and performed by them hereunder. |
| (b) | The execution, delivery and performance of this Agreement does not contravene any law, rule or regulation of either Party or of the jurisdiction in which it is incorporated. |
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| (c) | UTIF is a corporation duly organized, validly existing and in good standing, and it has the right and authority to enter this Agreement and the right to grant the license as provided herein and that such grant is not in conflict with any other agreement to which it is a party. |
EXCEPT FOR THE FOREGOING REPRESENTATIONS AND WARRANTIES PROVIDED IN THIS SECTION 5.1, UTIF DISCLAIMS ALL REPRESENTATIONS, WARRANTIES AND CONDITIONS OF ANY KIND, WHETHER EXPRESS OR IMPLIED, STATUTORY OR OTHERWISE, INCLUDING WITHOUT LIMITATION ALL REPRESENTATIONS, WARRANTIES AND CONDITIONS AS TO QUALITY, MERCHANTABLE QUALITY, MERCHANTABILITY OR FITNESS FOR ANY PARTICULAR PURPOSE, SCOPE, PATENTABILITY, VALIDITY OR ENFORCEABILITY OF THE TECHNOLOGY OR THAT THE TECHNOLOGY IS SAFE FOR ANY USE OR PURPOSE WHATSOEVER, OR THAT THE TECHNOLOGY DOES NOT INFRINGE THE RIGHTS OF ANY THIRD PARTY.
| 5.2 | Indemnity |
Licensee shall indemnify and hold harmless the Owners, their successors and assigns, and UTIF and the University, including their parents, subsidiaries, affiliates, attorneys, agents, officers, directors, employees, administrators, predecessors, successors or assigns (collectively, the Indemnities) from and against any and all claims, threats, loss, liability, damage or expense, including reasonable lawyers fees, by reason or arising out of any acts or failure to act by or out of any use of Technology, Patents or Licensed Products by sub-licensees or by Licensee or their respective servants, agents, Affiliates, officers, directors, stock-holders, employees, or customers. The party seeking indemnification shall give the Licensee prompt notification of any such claim, threat, loss, liability, damage or expense. The indemnity provided herein shall survive any termination or assignment of this Agreement without time limit. Licensee acknowledges that UTIF is entering this Agreement and obtaining for foregoing indemnification as agent for the other Indemnities and is holding the rights contained in this paragraph in trust for the other Indemnities.
| 5.3 | Insurance |
| (a) | Licensee, at its own expense and at all times, during the term of this Agreement and for the duration of its indemnity obligations which survive the expiration or premature termination of this Agreement pursuant to Section 5.2 herein, shall carry and maintain in full force and effect comprehensive general liability insurance in amounts not less than $1,000,000 per incident and $2,000,000 annual aggregate, naming UTIF, the University and the Owners as additional insureds. Prior to entering human clinical trials Licensee shall add product liability provisions, and Licensee shall increase the amounts of the insurance policy referred to hereinabove to $5,000,000 per incident and $5,000,000 annual aggregate. |
| (b) | The coming into force of this Agreement is conditional upon UTIF having received a certificate of insurance from the insurance company, in a form acceptable to UTIF, within thirty (30) days following the Effective Date. Such |
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| policy shall contain an endorsement by the insurer providing that it shall not be reduced below the stated minimum, cancelled or amended without thirty (30) days prior notice to UTIF.
ARTICLE 6
TERM AND TERMINATION
| 6.1 | Term |
This Agreement shall come into effect upon the Effective Date, and unless earlier terminated, shall terminate on the expiration or invalidity of the last issued Patent.
| 6.2 | Termination |
| (a) | The occurrence of anyone or more of the following events shall constitute an event of termination of this Agreement and shall, in addition to any other right or remedy either Party may have, permit a Party hereto to immediately terminate this Agreement: |
| (i) | if the other Party breaches any material covenant or obligation in this Agreement, other than a breach of the Milestones as specified in section 3.2 herein, and such breach is not fully remedied within thirty (30) days after the Party in breach receives written notice of such breach from the other Party; or |
| (ii) | if Licensee fails to provide UTIF with a certificate of insurance pursuant to Section 5.3 (b) herein; or |
| (iii) | in the event of any adjudication of bankruptcy, appointment of a receiver by a Court of competent jurisdiction, assignment for the benefit of creditors, involving the other Party either voluntary or involuntary, or appointment of a receiver by the other Party for any reason whatsoever. Such termination shall not impair or prejudice any other right or remedy that UTIF may otherwise have under this Agreement. |
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| (b) | Licensee may, at its sole discretion, terminate this Agreement upon thirty (30) days prior written notice to UTIF in the event that UTIF elects to make this license non-exclusive pursuant to Section 3.2 (d) herein. |
| (c) | UTIF may, at its sole discretion, terminate this Agreement upon thirty (30) days prior written notice to Licensee in the event that Licensee does not Secure a minimum of two hundred and forty-seven thousand and two hundred dollars ($247,200) within six (6) months following the Effective Date of this Agreement. |
| (d) | Termination as set forth in this Section shall not relieve any of the Parties of any obligations accrued under this Agreement prior to the date of termination. The following provisions shall survive termination of this license: Sections 3.3 (Accounting & Records); 4.1 (Ownership); 4.6 (Confidentiality); 5.2 (Indemnity); 5.3 (Insurance); 5.4 (Limitation of Liability); 6 (Termination and Effect of Termination); and 7 (General Provisions). |
| 6.3 | Effect of Termination |
Upon termination of this Agreement, Licensee shall forthwith:
| (a) | cease use of Technology and Licensed Products; |
| (b) | pay promptly all amounts it owes to UTIF; |
| (c) | assign any and all sub-licenses granted under this Agreement to UTIF; and |
| (d) | subject to Section 4.6 (e) herein, return to UTIF all Confidential Information. |
ARTICLE 7
GENERAL
| 7.1 | Time |
Time is of the essence of each provision of this Agreement.
| 7.2 | Assignment and Sub-licenses |
| (a) | Neither Party may sell, assign, encumber, license or otherwise transfer any of its rights, duties or obligations hereunder without the prior written consent of the other Party, which consent shall not be unreasonably withheld. Notwithstanding the foregoing, either Party may assign its rights and obligations hereunder to a entity acquiring all, or substantially all of such Partys business or assets without the prior consent of the other Party. |
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| (b) | The Licensee is responsible for any and all activities of any sub-licensee and the sub-licensee shall adhere to all confidentiality, indemnity and insurance requirements set forth in this Agreement. No sub-license granted by Licensee shall be less favorable with respect to any term or condition to UTIF than the license granted herein. |
| 7.3 | Notices |
Any notice, demand or other communication required or permitted to be given or made hereunder shall be in writing and shall be sufficiently given or made if delivered personally or sent by prepaid registered mail to its address or by telecopier to the number and to the attention of the person set forth below:
| (a) | In the case of a notice to Licensee: |
Protagenic Therapeutics, Inc.
4264 Corte Favor,
San Diego, California,
92130
Attention: President
Telecopier No.: ()
With a copy to:
John D. Tishler
Sheppard Mullin Richter & Hampton LLP
12544 High Bluff Drive, Suite 300
San Diego, CA 92130
Telecopier No.:<PHONE_NUMBER>
| (b) | In the case of a notice to UTIF: |
University of Toronto Innovations Foundation
243 College Street, Suite 200
Toronto, Ontario
M5T lR5
Canada
Attention: Executive Director
Telecopier No:<PHONE_NUMBER>
Each notice sent in accordance with this Section shall be deemed to have been given and received:
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| (i) | if delivered, on the day it was delivered if received within normal business hours; |
| (ii) | if mailed, on the fifth business day following the date on which it was mailed, unless an interruption of postal services occurs or is continuing on or within the five business days after the date of mailings in which case the notice shall be deemed to have been received on the fifth business day after postal service resumes; |
| (iii) | if sent by telecopier, on the day it was received, or on the first business day thereafter if the day on which it was sent was not a business day or outside normal business hours. |
Either Party may by notice to the other, given as aforesaid, designate a changed address or telecopier number.
| 7.4 | Conflict |
In the event any term or any part of any term of this Agreement is determined to be void or unenforceable, such term or part of a term shall be considered separate and severable from this Agreement and the remaining terms shall continue in full force and effect.
| 7.5 | Governing Law & Attornment |
This Agreement shall be interpreted and construed in accordance with the laws of the Province of Ontario and the laws of Canada applicable therein, and each Party hereby attorns and submits to the non-exclusive jurisdiction of the courts of the Province of Ontario, Canada.
| 7.6 | Further Assurances |
The Parties agree to execute, acknowledge and deliver all such further instruments, and to do all such other acts, as may be necessary or appropriate to carry out the intent and purpose of this Agreement.
| 7.7 | Waiver of Rights |
The failure of a Party at any time to request the other Party hereto to comply with any of the terms, conditions or covenants hereof shall not be deemed a waiver of such terms, conditions or covenants. Waiver by a Party of a breach of any term or condition of this Agreement shall not be considered a waiver of any subsequent breach of the same or of any other term or condition hereof.
| 7.8 | Relationship of the Parties |
| (a) | The relationship of Licensee to UTIF is that of an independent contractor and neither Licensee nor its agents or employees shall be considered employees of UTIF. This Agreement does not constitute and shall not be construed as constituting a partnership or joint venture or grant of a franchise between Licensee and UTIF. |
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| (b) | A Party will not use the name of any other Party, nor any member of such Partys staff in any advertising or publicity without the prior written approval of an authorized representative of the body whose name is to be used. However, a Party may notify others of the fact that this Agreement is in effect. |
| 7.9 | Force Majeure |
No Party shall be liable to any other party for delay or failure in the performance of any of its obligations hereunder if such failure is caused by Force Majeure, as hereinafter defined. For the purposes hereof, Force Majeure means any act of God, action or failure to act of any government or governmental or regulatory authority, failure of supplies, materials, equipment, labour or transportation being provided by any other person, power failure or shortage, strike, lockout, work slowdown or stoppage, accident, fire, flood, explosion, storm, other natural occurrence, sabotage or other event beyond the control of the relevant party.
| 7.10 | Rights and Remedies |
In the event that there is a dispute regarding any covenant or obligation in this Agreement, a Party shall be entitled to exercise any right or remedy available to it at law. Such rights shall include, without limitation, termination of this Agreement, and damages.
| 7.11 | Entire Agreement |
This Agreement, including all attached Schedules which are hereby incorporated by reference, sets forth the entire agreement and understanding of the Parties relating to the subject matter contained herein and merges all prior discussions and agreements between them, and neither Party shall be bound by any definition, condition, warranty or representation other than expressly stated in this Agreement. Any amendment to this Agreement shall not be effective unless it is in writing and signed by the duly authorized signing officers of each Party.
| 7.12 | Facsimile Execution |
To evidence the fact that it has executed this Agreement, a Party may send a copy of its executed counterpart to the other Party by facsimile transmission. That Party shall be deemed to have executed this Agreement on the date it sent such facsimile transmission. In such event, such Party shall forthwith deliver to the other Party the counterpart of this Agreement executed by such Party.
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| 7.13 | Succession |
This Agreement shall be binding upon and enure to the benefit of the Parties hereto and their respective successors and assigns.
IN WITNESS WHEREOF, the Parties have caused this Agreement to be executed in a legally binding manner.
UNIVERSITY OF TORONTO INNOVATIONS FOUNDATION
| Per: | /s/ Ron Venter | |
| Ron Venter, Ph.D. | ||
| Interim-Executive Director | ||
| PROTAGENIC THERAPEUTICS, INC. | ||
| Per: | /s/ Haro Hartounian | |
| Haro Hartounian | ||
| Assistant Secretary |
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Schedule A
Patent Applications
| Application No.: | PCT /CA03/00622 | |
| Title: | Teneurin C-Terminal Associated Peptides (TCAP) and Methods and Uses Thereof | |
| Inventors: | David Lovejoy, Bradley Chewpoy, Dalia Barsyte and Susan Rotzinger | |
| Filed: | May 2, 2003 |
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Schedule B
Research Agreement
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This RESEARCH AGREEMENT (the Agreement) is made and entered into as of December 14, 2004 (the Effective Date) by and between:
PROTAGENIC THERAPEUTICS, INC.
(the Company)
and
THE GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO
(the University)
WHEREAS, Professor David Lovejoy (Dr. Lovejoy) of the University of Toronto, Department of Zoology, has invented a proprietary genetic algorithm known as STORM for finding and predicting function(s) of novel therapeutic peptides that may be mimicked by small molecules, one such example of peptide is currently subject of the PCT patent application number PCT/CA03/0062 entitled TENEURIN C-TERMINAL ASSOCIATED PEPTIDES (TCAP) AND METHODS AND USES THEREOF (the Technology);
WHEREAS, Dr. Lovejoy has entered into an agreement with the University of Toronto Innovations Foundation (UTIF) in order to commercialize the Technology;
WHEREAS, UTIF entered into a Memorandum of Understanding (MOU) with the Company that outlines a plan for commercialization;
WHEREAS, a condition of the MOU is that the Company must enter into a licence agreement with UTIF for the Technology (the License Agreement), and a research agreement with the University to further develop the Technology, both agreements to be upon the terms set forth in the MOU.
WHEREAS, the University is prepared to undertake a research project entitled [[Project Title]] (the Project);
AND WHEREAS, the Company wishes to support the Project.
The Company and the University hereby agree as follows:
| 1. | Project. The University and the Principal Investigator (as defined below) shall perform the Project in accordance with this Agreement and the research plan set forth in Appendix A, as may be amended from time to time by mutual agreement of the parties in accordance with this Section 1 and Section 3 (the Research Plan). The initial Research Plan shall encompass the first six months ($52,800) of the Project. Prior to receipt of the second payment ($194,400) the Principal Investigator will be required to submit a revised Research Plan to the Company for its approval. Once the Company has approved the revised Research Plan, the Research Plan will be amended to reflect such revisions. At any time during the Term, the parties may amend the Research Plan upon mutual written agreement. |
| 2. | Term. The initial term of this Agreement shall commence upon the Effective Date and will end on the second (2nd) anniversary of the Effective Date, unless terminated earlier pursuant to Section 14 (the Term). The Term may be extended upon mutual agreement of the parties to include additional research beyond such initial two (2) year period. |
| 3. | Principal Investigator. The Principal Investigator for the Project shall be Dr. David Lovejoy. The Principal Investigator shall be responsible for the technical content of the Project and overseeing and managing the Project. So long as Dr. Lovejoy is an employee of the University and is willing to be the Principal Investigator, the University will maintain Dr. Lovejoy as the Principal Investigator; provided, however, that if Dr. Lovejoy becomes unavailable at any time during the Project, the University may nominate a replacement Principal Investigator, such nomination to be made within fourteen (14) days of the date on which Dr. Lovejoy becomes unavailable. If the Company, for any reason, does not accept the replacement Principal Investigator or a replacement Principal Investigator is not nominated by the University, the Research Plan may be amended to reflect a reduced scope of work for the Project, or the Agreement may be terminated by the Company as set forth in Section 14. |
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| 4. | Undertakings. |
(a) The University shall ensure that, prior to the commencement of the Project: (i) the Principal Investigator shall execute the Principal Investigators Undertaking (PIU,) attached hereto as Appendix C; (ii) any additional personnel, including without limitation, each additional investigator, involved in the Project (the Personnel) shall execute a Confidential Information and Intellectual Property Agreement (CIIP) substantially in the form attached hereto as Appendix D; and (iii) in the event that Dr. Lovejoy is replaced in accordance with Section 4 with a replacement Principal Investigator, the new Principal Investigator shall execute a PIU and each existing and new Personnel shall execute a CIIP under the replacement Principal Investigator.
(b) The University and Principal Investigator shall ensure that all work performed by such personnel on the Project is in compliance with the terms of this Agreement.
| 5. | Budget. In consideration of the University carrying out the Project, the Company shall pay the University the sum of CDN $247,200 and certain additional compensation all in accordance with the budget and payment schedule attached as Appendix B. |
| 6. | Payment. All cash payments shall be made by cheque payable to the University of Toronto and addressed to the Assistant Vice-President, Technology Transfer. The First Instalment (as defined in Appendix B) will be paid upon execution of this Agreement and the Second Instalment (as defined in Appendix B) shalt be paid upon the last to occur of the following: (i) February 31, 2005; (ii) the date which is two (2) months from the final execution of the Research Agreement; or (iii) the date which is two (2) months from the final execution of the Licence Agreement. |
| 7. | Equipment. The University will own any equipment or material purchased by or provided to the University as part of the Project. |
| 8. | Meetings and Reports. |
(a) The University through the Principal Investigator, the other investigators and any other appropriate Personnel will participate in bi-weekly telephone conversations, and at the discretion of the Company, monthly in-person meetings. Representatives of the Company shall be entitled to participate in such meetings.
(b) The University shall share all data, research work conclusions and recommendations arising from the performance of the Project (Research Results) with the Company, and shall provide reports regarding all Research Results as follows: (i) quarterly written reports, and more frequently upon specific request from the Company, presenting a meaningful summary of the research accomplished and comparing Research Results to the Research Plan, including without limitation, costs incurred with a comparison to Appendix B; and (ii) a fmal report within sixty (60) days after the end of the Term, or in the event the Term is extended, upon the end of such extended term.
(c) The Company shall have the right to use the Research Results and the reports (i) in connection with the research, development and commercialization of the Companys future products; (ii) to promote the Company; and (iii) as required for any regulatory submission or other submission to a government authority.
| 9. | Confidential Information. Each of the parties may disclose confidential information (the Disclosing Party) to the other party (the Receiving Party) to facilitate work under this Agreement. Such information (Confidential Information) shall be so identified in writing at the time of its transmittal to the Receiving Party, or so reduced to writing within ten (10) days thereafter. Confidential Information shall be maintained and held in strict confidence by the Receiving Party using the same methods and to the same degree of care (but at least reasonable care) that the Receiving Party uses to prevent disclosure of its own Confidential Information and shall not be |
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disclosed to third parties by the Receiving Party without the written consent of the Disclosing Party; provided, however, that the Receiving Party may disclose the Disclosing Partys Confidential Information to its agents, employees, officers, trustees, directors and representatives on a need-to-know basis (including, fulfilling corporate reporting obligations), as necessary to complete the Project in accordance with this Agreement, and only if the foregoing parties are bound in writing to be obligated by the same provisions of confidentiality and non-use with respect to such Confidential Information as are set forth herein. Confidential Information shall only be used by the Receiving Party for the purposes set forth in this Agreement, the MOU and the License Agreement. Confidential Information shall not include information that the Receiving Party can show by competent written evidence:
| (a) | is already known to the Receiving Party without any obligations of confidentiality; |
| (b) | is or becomes part of the public domain without breach of this Agreement; or, |
| (c) | is obtained from a third party who has no obligations of confidentiality to the parties to this Agreement. |
Notwithstanding the above, the Receiving Party may disclose Confidential Information, without violating the obligations of this Agreement, to the extent the disclosure is required by a valid court order or other governmental body having jurisdiction; provided that the Receiving Party gives reasonable prior written notice to the Disclosing Party of such required disclosure and makes a reasonable effort to obtain, or to assist the Disclosing Party in obtaining, a protective order preventing or limiting the disclosure and/or requiring that the Confidential Information so disclosed be used only for the purposes for which the law or regulation requires, or for which the order was issued.
| 10. | Intellectual Property. Any new intellectual property, including without limitation, technical information, know-how, copyrights, models, drawings, specifications, prototypes, inventions, improvements, discoveries, or software developed in performance of the Project (Intellectual Property) will be owned by the University. In accordance with the terms of the MOU, or following execution of the License Agreement, in accordance with the terms of the License Agreement, the Company shall have the option to exclusively license with rights of sub-license the Intellectual Property on the same royalty, sublicense fee and other terms as set forth in the MOU with respect to the licensing of the Technology to the Company. The option will be for one hundred eighty (180) days after disclosure of the Intellectual Property to the Company, and the license fee for such Intellectual Property, if the option is exercised, shall be equal to the out-of-pocket patent prosecution costs that the University, or its designate, has incurred with respect to such Intellectual Property prior to the exercise of such option. The Principal Investigator and all other Personnel are required to disclose all Intellectual Property to the University and any such disclosure shall also be made to the Company. The University, the Principal Investigator and all other Personnel shall execute all documents necessary and sufficient to enable the licensing of the Intellectual Property to the Company. The University reserves the non-transferrable, non-assignable, non-sublicenseable right to use the Intellectual Property for research, teaching and other administrative purposes upon terms to be more fully described in the License Agreement. |
| 11. | Publications. The University may publish or disclose the Research Results as permitted under this Section 11. Each such publication shall be authored as is scientifically appropriate and shall acknowledge the support of the Company in all such publications. The University will provide a copy of any proposed publication or disclosure to the Company for its review at least thirty (30) days before submission for publication or disclosure. Upon the Companys written request received within twenty (20) days of the Companys receipt of a copy of such publication or disclosure, the University will, at the Companys option: |
| (a) | delay publication up to sixty (60) additional days to enable the Company to secure intellectual property protection of Intellectual Property that would be publicly disclosed by said publication; and/or, |
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| (b) | delete any Confidential Information provided by Company from the manuscript or proposed disclosure. |
Prior to the earlier of completion of the First Research Milestone or termination of this Agreement, all publications or disclosures shall be made only upon the mutual agreement of the parties. For purposes of this Agreement, First Research Milestone shall mean identification of a single lead compound candidate ready for commencement of pre-clinical investigations.
| 12. | Indemnity. The Company shall indemnify, defend and hold harmless the University and its trustees, officers, directors, employees and agents from and against all claims, demands, suits or actions by third parties for any liability, loss, damage or cost (Losses) arising out of injuries (including death) to persons participating in the Project or damage to property, caused by agents or personnel of the Company during the performance of this Agreement, except to the extent such Losses are attributable to the wilful or negligent act or omission of personnel or agents of the University. The University shall indemnify, defend and hold harmless the Company and its directors, officers, employees and agents from and against all Losses arising from injuries (including death) to persons participating in the Project or damage to University property caused by the wilful or negligent act or omission of personnel or agents of the University during the performance of this Agreement, except to the extent such Losses are attributable to the wilful or negligent act or omission of personnel or agents of the Company. The party seeking indemnity under this Section 12 shall promptly and in any event within thirty (30) days notify the indemnifying party of any known complaint, claim or injury which is the subject of a Loss by such indemnified party. The indemnified party shall, and shall ensure that any fellow indemnitees, cooperate with the indemnifying party in the defense or settlement of any claim of Loss under this Section 12; provided, however, that no indemnitee shall be required to admit fault or responsibility in connection with any settlement. The indemnified party shall have the right to select and to obtain representation by separate legal counsel at such indemnified partys own expense. |
| 13. | Representations and Warranties; Limitation of Liability. |
| (a) | Each party represents and warrants that the terms of this Agreement are not inconsistent with its other contractual arrangements or obligations. |
| (b) | Each party represents and warrants that (i) it has the full power and authority to enter into this Agreement, (ii) this Agreement has been duly authorized, and (iii) this Agreement is binding upon it. |
| (c) | The University shall not be liable for any delays in the performance of its obligations under this Agreement resulting from circumstances or causes beyond the Universitys control, and in no case shall the University be liable for loss of business or profit or other indirect or consequential damage. |
| 14. | Termination. This Agreement may be terminated as follows: |
| (a) | by the University upon giving sixty (60) days written notice to the Company, if, in the reasonable judgement of the Principal Investigator, the research program is no longer technically feasible; |
| (b) | by the Company upon giving sixty (60) days written notice to the University if, in the reasonable judgement of the Company, the research program is no longer technically or commercially feasible; |
| (c) | by the Company upon giving thirty (30) days written notice to the University if, at any time during the Term or any extension thereof, the parties are unable to agree on the terms of an amendment to the Research Plan; |
| (d) | by the Company immediately upon giving written notice to the University if (i) the Company does not accept the replacement Principal Investigator nominated by the University or (ii) if no replacement Principal Investigator is nominated by the University within fourteen (14) days of the date on which Or. Lovejoy becomes unavailable; |
-4-
| (e) | by the Company upon giving thirty (30) days written notice to the University if a research milestone has not been achieved within the time period specified in the Research Plan; or, |
| (f) | by either party upon giving thirty (30) days written notice to the other if the other party is in default of fulfilling any of its obligations under this Agreement and such default has not been cured within such thirty (30) days notice period. |
Upon termination, the University will be entitled to credit for work performed hereunder prior to such termination, including all non-cancellable costs incurred by the University prior to the date of notice of termination, and the Company will be entitled to a return of the remaining balance of any advance payment. The University shall use reasonable efforts, and shall ensure that the Principal Investigator uses reasonable efforts, to minimize the non-cancellable costs and expenses associated with the termination of the Agreement. Upon termination, the Company may, in its sole discretion, pursue research under the Research Plan beyond the First Research Milestone outside of this Agreement. Expiration or termination of this Agreement will not relieve the parties of any obligation accruing prior to such expiration or termination. Sections 5, 6, 8, 9, 10, 11, 12, 13(c), 14, 15, 16, 17, 18, 19, 20 and 21 will survive termination of this Agreement.
| 15. | No Use of Names. Neither party win use the name of the other party, or of any member of the other partys personnel, in any advertising or publicity without the prior written approval of the other partys authorized representative. However, both parties may make the following information a matter of public record: name of the Principal Investigator; the Principal Investigators department; the Universitys name; the Companys name; the Project title; and the Project duration. |
| 16. | Notices. Notices under this Agreement will be sent to the appropriate party at the address specified below, with copies to the additional addresses for such party specified below, or at such other address(es) as the party shall specify in writing: |
| (a) | to the University: |
| i. | for technical and scientific matters: |
Professor David Lovejoy
Department of Zoology
Faculty of Arts and Science
25 Harbord Street, RW305
Toronto, Ontario, M5S 3G5
:<PHONE_NUMBER>
| ii. | for legal and administrative matters: |
Peter B. Munsche
Assistant Vice-President, Technology Transfer
University of Toronto Research Services
27 Kings College Circle
Toronto, Ontario M5S 1A1
:<PHONE_NUMBER> / :<PHONE_NUMBER>
| (b) | to Company: |
| i. | for scientific and technical matters: |
Protagenic Therapeutics, Inc.
Attn: Chief Scientific Officer
4264 Corte Favor
San Diego, CA 92103
-5-
: / :
| ii. | for legal and administrative matters: |
Protagenic Therapeutics, Inc.
Attn: Chief Operating Officer
4264 Corte Favor
San Diego, CA 92103
: / :
| iii. | with a copy to: |
John D. Tishler
Sheppard Mullin Richter & Hampton LLP
12544 High Bluff Drive, Suite 300
San Diego, CA 92130
:<PHONE_NUMBER> / :<PHONE_NUMBER>
| 17. | Independent Parties. The parties are independent parties and nothing in this Agreement shall constitute either party as the employer, principal or partner of or joint venturer with the other party. Neither party has any authority to assume or create any obligation or liability, either express or implied, on behalf of the other. |
| 18. | No Assignment. Neither party may sell, assign, encumber, licence or otherwise transfer any of its rights, duties or obligations under this Agreement without the prior written consent of the other party, which consent may not be unreasonably withheld. Notwithstanding the foregoing, the Company may assign its rights or obligation to an entity acquiring all, or substantially all of the Companys business or assets without obtaining the consent of the University. |
| 19. | Successors. This Agreement shall binding and enure to the benefit of the parties and their respective heirs, successors and assigns. |
| 20. | Governing Law. This Agreement shall be governed by and construed in accordance with the laws of Canada and the laws of the Province of Ontario applicable therein. |
| 21. | Entire Agreement. This Agreement is the entire agreement of the parties and no change or modification shall be valid unless it is in writing and signed by both parties. |
In witness whereof the parties agree to be bound by the terms of this Agreement.
| THE GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO |
PROTAGENIC THERAPEUTICS, INC. | |||||
| /s/ Peter Munsche |
/s/ H. Hartounian | |||||
| Name: | Peter Munsche | Name: | H. Hartounian | |||
| Title: | Vice-President, Technology | Title: | Chairman | |||
| Transfer |
-6-
PRINCIPAL INVESTIGATOR:
I, the Principal Investigator, having read this Agreement, hereby agree to act in accordance with all the terms and conditions herein and further to agree to ensure that all University participants are informed of their obligations under such terms and conditions.
| /s/ David Lovejoy |
| Professor David Lovejoy, University of Toronto, Department of Zoology |
-7-
APPENDIX A
Research Plan
Dr. D.A. Lovejoy: Research Plan
for Protagenic Therapeutics, Inc.
Phase I Funding
Time Scale: 6 months from onset of funding
PROJECT TITLE: Evidence for existence of TCAP receptors in neurons.
GOALS:
| 1) | Determination of the most appropriate cell line to evaluate TCAP ligand affinity for its receptor. |
| 2) | Determination of cell lines that do not have TCAP receptors |
| 3) | Determination of the most appropriate cell line in which to purify the TCAP receptor |
Background: The identification of eventual structural characterization of high affinity TCAP receptors are essential to develop a high sensitivity ligand-screening assay for the purpose of evaluating future TCAP peptide variants and ultimately as a high-throughput testing platform to develop TCAP small molecule mimics. We have a unique advantage to develop a distinct receptor-screening assay by capitalizing on the use of the recently developed immortalized hypothalamic cell lines. We have screened these cells for TCAP responsiveness and identified four cell lines that are responsive to TCAP as determined by cAMP modulation abilities. However, we have determined that cAMP is not a reliable endpoint as an evalution method. Many hormones can trigger an increase in cAMP in some parts of the cell, for example neurites and axon hillock regions, but a decrease in dentrites. Thus using a monoculture of cells can lead to inconsistent results depending upon the confluency, passage and growth rate of the cultured cells. Ligand-binding determinations are a more reliable determination as a first level of evalution of ligand activity because receptor activation is a prerequisite for downstream cellular activity such as cAMP.
Experimental Design: Plasma membrane preparations of four different mouse neuronal cell line cultures will be used to measure the affinity of mouse TCAP-l for the endogenous receptor. Cells will be grown initially to 50 to 60% confluency, as we have previously determined that this cell density is the most consistent in terms of TCAP action using neurite outgrowth and cAMP as physiological endpoints. Receptor affinity will be evaluated using two methods: 1) Scintillation proximity assays (SPA) and 2) radioreceptor assays. The scintillation assay has the advantage in that it is already designed to be a high throughput method. It has the disadvantage in that it has a lower sensitivity than other methods, and so the optimization of the cell type and receptor expression level are key requirements for an effective method. We have used this method in the past with ectopically expressed receptors in a rapidly growing cell line. The radioreceptor assay, on the other hand is highly sensitive and specific using a radiolabelled TCAP ligand. We have used this method in the past to evaluate small sequence changes in peptides with a similar structure to TCAP. The disadvantage of this method is that it cannot be readily scaled up to a high-throughput level. Thus for the purposes of defining the level of TCAP receptor expression and its affinity for its ligand, both methods are complementary.
-8-
Goal 1: Determination of the most appropriate cell line to evaluate TCAP ligand affinity for its receptor.
TCAP affinity determined by as strong response using the SPA assay, and confirmed by the radioreceptor assay will be selected as the cell line for high throughput screening
Goal 2: Determination of cell lines that do not have TCAP receptors.
A negative response in the form of a flat displacement curve for both assays will be used as evidence that the TCAP receptor is not present. As further confirmation of this, a cAMP assay will be employed.
Goal 3: Determination of the most appropriate cell line in which to purify the TCAP receptor
Cell lines showing a strong affinity curve with a single binding site will be selected to for the purification of the receptor. Proteins with affinity for TCAP will be examined using ligand photoaffinity crosslinking to the bound protein.
Challenges and Interpretation: Although we already possess cell lines with the TCAP receptor that can yield a measurable response, high levels of receptor expression are essential for a sensitive screening assay. Endogenously expressed receptors may not be expressed at a level that is viable for a screening assay that can be scaled up to a high-throughput type level. In this case, it may be necessary to explore additional heterologous systems where the TCAP receptor is ectopically expressed in for example non-neural cells using a vector system incorporating a high expression promotor (e.g. CMV). We have utilized a similar system in the past to evaluate novel peptide designs and, therefore, have the experience to develop this further, if necessary. Our preliminary investigations also indicate that the affinity of the TCAP receptor may be altered by the presence of GPCR-modulating proteins, particularly the RAMP proteins. Thus, if using a heterologous expression system, the appropriate RAMP may have to be coexpressed. Alternatively, if receptor levels are of sufficiently high levels in the homologous neuronal systems, then using the appropriate cell line with the requisite accessory proteins will be essential.
Timelines
The setting up and optimization of the receptor assay systems are expected to take about 2 months. Determination of the appropriate cell lines are expected to take 2-4 months depending of the data obtained. Within this period we will know whether an endogenously expressed receptor system or an ectopically expressed receptor system is more sensitive to evaluate the compounds. About 2 to 4 months will be required to evaluate the levels of TCAP bound protein in the responsive cell lines. A number of the project goals can be done in parallel to each other such that about 6 months will be required to answer these questions.
Personnel: An entry-level post-doctoral scientist with a background in molecular pharmacology will be responsible for the setting up and optimization of the assay, as well as the analysis of the peptide binding curves. This individual will also be responsible for organizing the testing regimens and in consultation with Dr. Lovejoy making the decision on the appropriate cell lines and preparing the data reports. A junior research assistant is will be required for the preparation and maintenance of the cell lines as well as assist as necessary in the preparation of the cell and membrane extracts. The scientist in training, Arij Al Chawaf, presently a Ph.D student in Dr. Lovejoys laboratory, who has been developing the receptor characterization assays will evaluate the cell lines selected for the purification of the receptor using photoaffinity crosslinking purification.
-9-
Phase / Budget: Evalution of TCAP receptor affinity in immortalized neurons
| Personnel |
Post Doctoral Scientist | 21,000 | ||||
| Research Assistant | 12,500 | |||||
| Scientist in training | 2,000 | |||||
| total | 35,500 | |||||
| Consumables |
SPA kits | 7,000 | ||||
| Radioisotopes | 2,500 | |||||
| disposable labware | 800 | |||||
| chemicals | 500 | |||||
| Electrophoresis | 5500 | |||||
| Tissue culture | 1000 | |||||
| total | 17,300 | |||||
| grand total | 52,800 |
-10-
APPENDIX B
Budget
Cash Payment
| First Installment | Second Installment | |||||||
| Direct Costs |
CDN$ | 45,913 | CDN$ | 169,043 | ||||
| O/H Cash |
CDN$ | 6,887 | CDN$ | 25,357 | ||||
|
|
|
|
|
|||||
| Total Cash |
CDN$ | 52,800 | CDN$ | 194,400 | ||||
|
|
|
|
|
Additional Consideration
As consideration for an overhead cost of 15% of direct costs for a two (2) year period beginning on the Effective Date, the University shall receive an option to purchase 30,000 shares of the Companys Common Stock, representing 3% of the Companys outstanding Common Stock upon formation, at an exercise price of US$1.00 per share (the Options). Commencing on the Effective Date, the Options shall vest on a monthly basis over a two (2) year period, subject to continuation of research by the University under this Agreement, so that 1/24th of the Options shall vest each month during such two (2) year period. The Options shall expire on August 31, 2009.
-11-
APPENDIX C
Principal Investigators Undertaking
| Please return the signed original of this Undertaking to Melissa Jutzi at Research Services, Simcoe Hall, Rm. 133S, who can be reached at 978-6927 for information about the Research Agreement.
20/01/99 |
PRINCIPAL INVESTIGATORS UNDERTAKING
| RE: | Contract between the University of Toronto and Protagenic Therapeutics, Inc. for a project entitled [[Project Title]] (the Project) |
UNDERTAKING
I have read and received a copy of the above referenced agreement (the Research Agreement) and agree with the terms and conditions contained therein. I will ensure that the Project is performed as outlined in the Research Agreement and will meet the obligations as specified in the Research Agreement. I will authorize all project expenditures as outlined in the Research Agreement and the normal procedures and practices of the University, and in all matters will follow normal University policies and practices where they are not replaced by specific conditions of the Research Agreement.
I will inform each person working on the Project, whether or not paid from Research Agreement funds (the Participant), of the Participants obligations under the Research Agreement, and ensure that each Participant signs a Confidential Information and Intellectual Property Agreement in the form attached as Appendix D to the Research Agreement (IP Agreement). I understand that any person who does not wish to sign an IP Agreement may not participate in the Project unless the Universitys Office of Research Services advises otherwise.
A list of Participants is provided on the reverse and a signed IP Agreement for each Participant is attached. I have indicated on the reverse if any Participants work involves his or her thesis. If any person not listed on the reverse commences work on the Project, I will submit an additional IP Agreement for such person promptly upon his or her commencement of work, and I shall update the list of Participants to include any such person.
| /s/ David Lovejoy |
| Name: Professor David Lovejoy, Principal Investigator |
| Date: December 9, 2004 |
| ACKNOWLEDGEMENT |
| /s/ James D. Thomson |
| Name: Professor James D. Thomson, Chair, Department of Zoology |
| Date: 9 December 2004 |
-12-
Appendix C-l
Project Participants
| RE: Agreement with Sponsor: | Protagenic Therapeutics, Inc. | |||
| for Project: | ||||
| by Principal Investigator: | Professor David Lovejoy |
The following is a complete list of all persons who are working on the Project, whether or not paid from Research Agreement funds, as of (Date).
(student, postdoc, RA, technician, etc.)
| Name |
Status |
Involves Thesis | ||
| ARIJ AL CHAWAF |
PHD STUDENT | YES |
20/01/99
-13-
APPENDIX D
Form of Confidential Information & Intellectual Property Agreement
| Each person working on the project, whether or not paid from Research Agreement funds, must sign and date this agreement. Please return a signed original of this agreement to Melissa Jutzl at Research Services, Simcoe Hall, Rm. 133S, who can be reached at 978-6927 for information about the Research Agreement.
20/01/99 |
Confidential Information & Intellectual Property Agreement
The University of Toronto (the University) may make information and facilities for research available to me in connection with my work under a contract between the University and Protagenic Therapeutics, Inc. (the Sponsor) for the project entitled [[Project Title]] (the Research Agreement). Dr. David Lovejoy will supervise my work.
In consideration of information and facilities made available to me and other valuable consideration, I agree that:
| 1. | I will keep confidential, in accordance with the terms of the Research Agreement, all of the Sponsors confidential information that I may receive. I will also keep the terms of the Research Agreement confidential. |
| 2. | I will comply with all publication conditions that may be set out in the Research Agreement. |
| 3. | I will give complete information to the Universitys Office of Research Services about any intellectual property, including without limitation, any technical information, know-how, copyright, model, drawing, specification, prototype, invention, improvement, discovery, or software that I may make, conceive, develop, or reduce to practice in performance of the project (Intellectual Property) as may be requested by the University. |
| 4. | I will comply with all conditions regarding Intellectual Property that may be set out in the Research Agreement. |
| 5. | All decisions about the protection of Intellectual Property under applicable legislation, ownership of and rights in any resulting application or patent, and revenue from Intellectual Property will be made in accordance with the University of Toronto Inventions Policy dated effective January 1, 1990, as amended (http://www.research.utoronto.ca/policies_inventions.html). and/or the University of Toronto Copyright Policy dated June 3, 2002, as amended (http://www.research.utoronto.ca/copyright.html), and the Research Agreement, and I will accept such decisions as final. |
| 6. | I will sign all documents and do all things necessary or proper to give effect to this Agreement and any rights granted by the University under the Research Agreement. |
| 7. | I have had an opportunity to review the applicable terms of the Research Agreement and obtain independent advice on the terms of the Research Agreement and my obligations and liabilities under this Agreement and the Research Agreement. |
| 8. | This Agreement shall be binding on my heirs. |
-14-
By signing below, I indicate my acceptance of these terms.
| /s/ David Lovejoy |
/s/ Gina Trubiani |
|||||
| Signature | Witness | |||||
| David Lovejoy |
Gina Trubiani |
|||||
| Name (Type or Print) | Name (Type or Print) | |||||
| December 16, 2004 |
December 16, 2004 |
|||||
| Date | Date |
-15-
Dr. D.A. Lovejoy: Research Plan
for Protagenic Therapeutics, Inc.
Phase I Funding
Time Scale: 6 months from onset of funding
PROJECT TITLE: Evidence for existence of TCAP receptors in neurons.
GOALS:
| 1) | Determination of the most appropriate cell line to evaluate TCAP ligand affinity for its receptor. |
| 2) | Determination of cell lines that do not have TCAP receptors |
| 3) | Determination of the most appropriate cell line in which to purify the TCAP receptor |
Background: The identification of eventual structural characterization of high affinity TCAP receptors are essential to develop a high sensitivity ligand-screening assay for the purpose of evaluating future TCAP peptide variants and ultimately as a high-throughput testing platform to develop TCAP small molecule mimics. We have a unique advantage to develop a distinct receptor-screening assay by capitalizing on the use of the recently developed immortalized hypothalamic cell lines. We have screened these cells for TCAP responsiveness and identified four cell lines that are responsive to TCAP as determined by cAMP modulation abilities. However, we have determined that cAMP is not a reliable endpoint as an evalution method. Many hormones can trigger an increase in cAMP in some parts of the cell, for example neurites and axon hillock regions, but a decrease in dentrites. Thus using a monoculture of cells can lead to inconsistent results depending upon the confluency, passage and growth rate of the cultured cells. Ligand-binding determinations are a more reliable determination as a first level of evalution of ligand activity because receptor activation is a prerequisite for downstream cellular activity such as cAMP.
Experimental Design: Plasma membrane preparations of four different mouse neuronal cell line cultures will be used to measure the affinity of mouse TCAP-l for the endogenous receptor. Cells will be grown initially to 50 to 60% confluency, as we have previously determined that this cell density is the most consistent in terms of TCAP action using neurite outgrowth and cAMP as physiological endpoints. Receptor affinity will be evaluated using two methods: 1) Scintillation proximity assays (SPA) and 2) radioreceptor assays. The scintillation assay has the advantage in that it is already designed to be a high throughput method. It has the disadvantage in that it has a lower sensitivity than other methods, and so the optimization of the cell type and receptor expression level are key requirements for an effective method. We have used this method in the past with ectopically expressed receptors in a rapidly growing cell line. The radioreceptor assay, on the other hand is highly sensitive and specific using a radiolabelled TCAP ligand. We have used this method in the past to
evaluate small sequence changes in peptides with a similar structure to TCAP. The disadvantage of this method is that it cannot be readily scaled up to a high-throughput level. Thus for the purposes of defining the level of TCAP receptor expression and its affinity for its ligand, both methods are complementary.
Goal 1: Determination of the most appropriate cell line to evaluate TCAP ligand affinity for its receptor.
TCAP affinity determined by as strong response using the SPA assay, and confirmed by the radioreceptor assay will be selected as the cell line for high throughput screening
Goal 2: Determination of cell lines that do not have TCAP receptors.
A negative response in the form of a flat displacement curve for both assays will be used as evidence that the TCAP receptor is not present. As further confirmation of this, a cAMP assay will be employed.
Goal 3: Determination of the most appropriate cell line in which to purify the TCAP receptor
Cell lines showing a strong affinity curve with a single binding site will be selected to for the purification of the receptor. Proteins with affinity for TCAP will be examined using ligand photoaffinity cross linking to the bound protein.
Challenges and Interpretation: Although we already possess cell lines with the TCAP receptor that can yield a measurable response, high levels of receptor expression are essential for a sensitive screening assay. Endogenously expressed receptors may not be expressed at a level that is viable for a screening assay that can be scaled up to a high-throughput type level. In this case, it may be necessary to explore additional heterologous systems where the TCAP receptor is ectopically expressed in for example non-neural cells using a vector system incorporating a high expression promotor (e.g. CMV). We have utilized a similar system in the past to evaluate novel peptide designs and, therefore, have the experience to develop this further, if necessary. Our preliminary investigations also indicate that the affinity of the TCAP receptor may be altered by the presence of GPCR-modulating proteins, particularly the RAMP proteins. Thus, if using a heterologous expression system, the appropriate RAMP may have to be coexpressed. Alternatively, if receptor levels are of sufficiently high levels in the homologous neuronal systems, then using the appropriate cell line with the requisite accessory proteins will be essential.
Timelines
The setting up and optimization of the receptor assay systems are expected to take about 2 months. Determination of the appropriate cell lines are expected to take 2-4 months depending of the data obtained. Within this period we will know whether an endogenously
expressed receptor system or an ectopically expressed receptor system is more sensitive to evaluate the compounds. About 2 to 4 months will be required to evaluate the levels of TCAP bound protein in the responsive cell lines. A number of the project goals can be done in parallel to each other such that about 6 months will be required to answer these questions.
Personnel: An entry-level post-doctoral scientist with a background in molecular pharmacology will be responsible for the setting up and optimization of the assay, as well as the analysis of the peptide binding curves. This individual will also be responsible for organizing the testing regimens and in consultation with Dr. Lovejoy making the decision on the appropriate cell lines and preparing the data reports. A junior research assistant is will be required for the preparation and maintenance of the cell lines as well as assist as necessary in the preparation of the cell and membrane extracts. The scientist in training, Arij Al Chawaf, presently a Ph.D student in Dr. Lovejoys laboratory, who has been developing the receptor characterization assays will evaluate the cell lines selected for the purification of the receptor using photo affinity cross-linking purification.
Phase / Budget: Evalution of TCAP receptor affinity in immortalized neurons
| Personnel |
Post Doctoral Scientist | 21,000 | ||||
| Research Assistant | 12,500 | |||||
| Scientist in training | 2,000 | |||||
| total | 35,500 | |||||
| Consumables |
SPA kits | 7,000 | ||||
| Radioisotopes | 2,500 | |||||
| disposable labware | 800 | |||||
| chemicals | 500 | |||||
| Electrophoresis | 5500 | |||||
| Tissue culture | 1000 | |||||
| total | 17,300 | |||||
| grand total | 52,800 |
AMENDING AGREEMENT #1 between
Protagenic Therapeutics, Inc. and the Governing Council of the University of Toronto
This AMENDING AGREEMENT (the Amending Agreement) made in duplicate the 31st day of May, 2005.
BETWEEN:
PROTAGENIC THERAPEUTICS, INC.
(the Company)
-and-
THE GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO
(the University)
WHEREAS the Company and the University entered into an agreement effective December 14, 2004 (the Research Agreement) for the performance of a research project entitled Evidence for existence of TCAP receptors in neurons (the Project);
AND WHEREAS the parties now wish to amend the Research Agreement herein;
The parties hereby agree as follows:
1. Definitions. Except as otherwise defined herein, any capitalized terms used in this Amending Agreement shall have the meanings prescribed by the Research Agreement The capitalized terms First Installment, Second Installment, and Final Installment shall have the meaning prescribed in Appendix B attached hereto.
2. Budget. The University has received $52,800 of the $247,200 due to the University for carrying out the Project. The Company shall provide the remaining budget of $l94,400 in accordance with the revised budget and payment schedule attached as Appendix B, which shall replace Appendix B of the Research Agreement.
3. Payment. The First Installment from the Company was paid by cheque on December 1, 2005. The Second Installment will be paid in equal installments over the six (6) month period of June 1, 2005November 31, 2005 on the first of every month. The Final Installment will be paid on the date which is six (6) months after the final execution of the License Agreement.
4. Research Plan. In accordance with Section 1 of the Research Agreement, the research plan set forth in Appendix A to the Research Agreement is supplemented by the research plan attached as Appendix A to this Amending Agreement.
5. Financial Reports. For six month period of the Second Installment, the University will provide the Company with financial reports from time to time summarizing the expenses incurred within a reasonable time after the Companys request therefor.
6. General. All other terms of the Research Agreement and the Administration Agreement shall remain unchanged and in full force and effect.
In witness whereof the parties agree to be bound by the terms of this Amending Agreement
| THE GOVERNING COUNCIL OF THE | PROTAGENIC THERAPEUTICS, INC. | |||||||
| UNIVERSITY OF TORONTO | ||||||||
| /s/ Peter B. Munsche |
/s/ H. Hartounian | |||||||
| Name: | Peter B. Munsche | Name: | H. Hartounian | |||||
| Title: | Assistant Vice-President | Title: | Chairman | |||||
| Technology Transfer |
Acknowledgement:
I, the Principal Investigator having read this Agreement, hereby agree to act in accordance with all the terms and conditions herein and to agree to ensure that all University participants are informed of their obligations under such terms and conditions.
| /s/ David Lovejoy |
| Prof. David Lovejoy, University of Toronto, Department of Zoology |
Appendix A
PTI Research Plan
Viability of TCAP as an Intravenously Injected Therapeutic
David Lovejoy and Susan Rotzinger
Strategy and Goals
The aim is to establish a complete physiological model of TCAP action from exogenous administration to the onset of behaviour with the goal to establish the feasibility of TCAP treatment on hospitalized patients suffering from severe depression or anxiety. Several experiments are proposed to fill in the gaps where the understanding of TCAP action is not complete.
At the completion of these studies, we should be able to determine the best method to administer TCAP, its longevity in vivo (biological half-life), its uptake in the brain, its mode of action on key sites in the brain and how it targets the CRF-mediated anxiogenic system, its actions on behavioural tests. Moreover, its actions on behavioural tests should allow predictions as to whether TCAP will be most appropriate for treating depression or anxiety.
Proposed Experiments
Development of New Assay Systems
In order to enhance our understanding of the actions of TCAP two new assay systems will be developed.
Forced Swim Test: Presently, our behavioural analyses are designed to evaluate the anxiolytic or anxiogenic aspects of bioreactive agents. However, the forced swim test is the industry standard test for evaluating whether an agent has the potential to modify the incidence of depression. This method is presently not being used in-house and therefore we need to purchase the necessary equipment and validate the test on TCAP treated animals in comparison to animals treated with agents known to enhance depression.
TCAP Radioimmunoassay: In addition, the accurate detection of TCAP in the blood stream may be a powerful tool to determine if individuals are predisposed to the incidence of depression and anxiety or are suffering from a condition associated with TCAP dysregulation. Moreover, a TCAP detection assay will allow for an understanding of the biological halflife of TCAP and in the future could be used to monitor patients undergoing TCAP treatment. If TCAP can be reliably detected in plasma then we envision using the ratio of plasma TCAP concentrations to known anxiogenic hormones such as CRF, ACTH and cortisol as a diagonostic means to detect the incidence of depression and anxiety. We have already raised three TCAP-specific antisera, and possess the necessary equipment to put this assay together.
page 1
Route of Administration
Presently most studies have focused on direct injection of TCAP into the brain using indwelling cannulae. Pilot studies indicate that intravenous injection is a viable method, although a full set of behavioural experiments to ascertain this have not been performed. In addition, subcutaneous injection has not been investigated.
TCAP will be administered either as a single injection IV or SC to determine acute effects, or as one injection each day over five days to determine chronic actions. The acoustic startle response, elevated plus maze, swim test behaviour locomotion and body weight changes will be examined
Biological Half-life
Nothing is presently known about the longevity of TCAP in vivo. A structural analysis of the peptide predicts that TCAP is modified for circulation in the blood stream. Two sets of experiments are designed to answer these questions.
Synthetic TCAP will be incubated in rat plasma, and its breakdown by proteolytic enzymes will be determined by examining the loss of immunoreactive signal on a high resolution polyacrylamide gel using TCAP-specific antisera over a 2 to 8 hour period. The length of time will be based on its rate of breakdown in the first 1 to 2 hours of the study. This will allow us to understand the plasma component of TCAP degradation.
Upon completion of the above experiments, TCAP will be injected intravenously into rats and the presence of TCAP in tissues and the brain will be examined by radioimmunoassay. TCAP expression
Tissue partitioning Studies
Pilot studies on IV injected TCAP reveal that this mode of administration induces behavioural changes consistent with the actions of neurally injected TCAP. This implies that TCAP is moving across the blood brain barrier to gain access into the brain, but does not rule out an indirect action of TCAP on other organ systems that possess a feedback action on the brain, for example the adrenal cortex.
TCAP uptake in the brain will be examined directly by the expression of labelled TCAP in the brain after IV injection of labelled TCAP. Any major modification of the TCAP sequence either by adding a novel epitope or by chemoluminescent tagging will likely modify TCAP uptake by putative transporter and receptor systems. Thus a radiolabel tag will likely be employed.
page 2
Interactions with CRF and its receptor system
The acoustic startle response studies indicate that TCAP may act directly on its own receptor to induce an anxiolytic response or alternatively may act as an antagonist on the CRF-receptor system to inhibit the actions of CRF. These studies are designed whether TCAP can directly inhibit the actions of CRF acutely or chronically through the CRF-R1 receptor system.
TCAP and CRF will be coinjected IV at varying concentrations to determine actions on ACTH release from the pituitary and cortisol release from the adrenal cortex. Previous studies by our laboratories indicate that TCAP by itself does not induce cortisol release. However a non-significant but compelling decrease in plasma cortisol was observed in animals treated with TCAP. These studies will be repeated in vitro using a cell line that possesses the CRF-R1 receptor.
Project Costs
| Project |
Experiment |
Item |
Description |
Total Cost | ||||||
| Administration Route |
Subcutaneous injection | Animals | 80 sprague dawley rats | $ | 2,235.20 | |||||
| Intravenous injection | Animals | 80 sprague dawley rats | $ | 2,235.20 | ||||||
| New behavior models |
Forced swim test | Animals equipment |
100 sprague dawley rats chambers |
$ $ |
2,794.00 1,000.00 |
| ||||
| In Vivo CRF-R1 studies |
TCAP/CRF interaction | Animals | 80 sprague dawley rats | $ | 2,235.20 | |||||
| Behavioural Studies |
General | Personnel | Full time animal technician | $ | 20,000.00 | |||||
| Consummables | Surgical supplies Pharmaceuticals Misc lab supplies |
$ $ $ |
4,000.00 1,000.00 1,000.00 |
| ||||||
| Development of TCAP assay |
Animals Consummables Consummables Consummables Consummables |
20 sprague dawley rats isotopes secondary antisera scintillation tubes and reagents misc lab supplies |
$ $ $ $ $ |
558.80 3,000.00 2,000.00 2,000.00 1,500.00 |
| |||||
| TCAP degradation studies |
In vivo | animals connsumables |
10 sprague dawley rats electrophoresis reagents |
$ $ |
279.40 2,500.00 |
| ||||
| In vitro | animals connsumables |
10 sprague dawley rats electrophoresis reagents |
$ $ |
279.40 1,000.00 |
| |||||
| TCAP partitioning studies |
Synthetic TCAP injection | Animals consummables consummables |
40 sprague dawley rats Radioimmunoassay reagents Misc lab supplies |
$ $ $ |
1,117.60 1,000.00 1,000.00 |
| ||||
| Peptide Studies |
General | personnel | Full time post doctoral scientest | $ | 17,500.00 | |||||
| Total |
$ | 70,234.80 |
page 3
Project Timeline
page 4
AMENDING AGREEMENT #1 between
Protagenic Therapeutics, Inc. and the Governing Council of the University of Toronto
APPENDIX B
Revised Budget
Cash Payment
| First Installment | Second Installment | Final Installment | ||||
| Direct Costs |
CDN$45,913 | CDN$70,235 | CDN$98,808 | |||
| O/H Cash |
CDN$6,887 | CDN$10,535 | CDN$14,822 | |||
| Total Cash |
CDN$52,800 | CDN$80,770 | CDN$113,630 |
Additional Consideration
As consideration for an overhead cost of 15% of direct costs for a two (2) year period beginning on the Effective Date, the University shall receive an option to purchase 30,000 shares of the Companys Common Stock, representing 3% of the Companys outstanding Common Stock upon formation, at an exercise price of US$1.00 per share (the Options). Commencing on the Effective Date, the Options shall vest on a monthly basis over a two (2) year period, subject to continuation of research by the University under this Agreement, so that 1/24th of the Options shall vest each month during such two (2) year period. The Options shall expire on August 31, 2009.
Schedule C
Milestones
| Event |
Payment | |||
| IND submitted after efficacy demonstrated in non-human primates (IND Submission), per IND candidate |
$ | 100,000 | ||
| Phase I End |
$ | 100,000 | ||
| Phase II End |
$ | 100,000 | ||
| Phase III End |
$ | 100,000 |
Page 23 of 24
Schedule D
University of Toronto Confidential Invention Disclosure
Page 24 of 24
Appendix A
| UNIVERSITY OF TORONTO INVENTIONS POLICY CONFIDENTIAL INTELLECTUAL PROPERTY DISCLOSURE Office of the Vice President Research and Associate Provost 27 Kings College Circle, Room 133-S Tel:<PHONE_NUMBER> Fax:<PHONE_NUMBER> email<EMAIL_ADDRESS>|
1. Title: Selected Targeting of Residue Motifs (STORM): a novel algorithmic method to predict bioactive peptides in genome databases
2. a) University of Toronto Inventors/Major Contributors:
| SURNAME, GIVEN NAMES | UNIVERSITY PERSONNEL NO. |
DEPARTMENT (LIST ANY CROSS APPOINTMENTS OR AFFILIATED INSTITUTIONS) |
AFFILIATION WITH UNIVERSITY (i.e., faculty, res. assoc., post- doc, student, staff, visitor, etc.) |
CURRENT ADDRESS, PHONE, FAX, EMAIL | ||||
| Lovejoy, David A. |
001012872 | Zoology | Faculty | 25 Harbord St t.<PHONE_NUMBER> f.<PHONE_NUMBER><EMAIL_ADDRESS>|
2. b) External Inventors/Major Contributors:
(Please provide names and affiliations of non-University of Toronto individuals who have made a creative contribution to this Intellectual Property, i.e. sponsor employees, academic collaborators, etc.)
No external inventors or contributors were part of the development of this intellectual property
3. Description:
(Please highlight the novelty or patentable aspects of this Intellectual Property; attach a separate sheet if necessary)
STORM is an algorithm to identify the functional regions in a peptide by examining the structure of orthologous peptides across taxa, and the structure of paralogous peptides within taxa. STORM is unique from other algorithmic methods to predict structure by its use of comparative phylogenetic information to determine the probability of particular amino acid substitutions within a sequence. Thus STORM utilizes animal phylogeny models based on both palaeontological data as well as molecular data. This information is used to construct a hypothetical functional ancestor where sets of common amino acid motifs are identified. The sequence and relative position of the motifs are used to search databases for related sequences. STORM can therefore be used to discover new bioactive proteins and peptides, new functions of known peptides and proteins, functional regions within peptides and proteins, and to design new peptides with novel properties.
| DATE RECEIVED: November 19, 2004 DISCLOSURE REFERENCE NO.: 10001238 |
Confidential Intellectual Property Disclosure (inventions Policy)
January/03
Page 1 of 2
4. How was the work leading to this Intellectual Property funded? i.e., salaries, equipment used, supplies, etc.
This work has not been funded.
| SPONSOR |
GRANT OR CONTRACT FUND # |
INTELLECTUAL PROPERTY TERMS & CONDITIONS | ||
| n/a |
n/a | n/a |
5. Where did the work leading to this Intellectual Property take place?
The STORM algorithm was developed entirely at the Dept of Zoology, University of Toronto, as a means of attempting to identify new families of peptides associated with stress and anxiety.
6. Is this Intellectual Property subject to any software licence, material transfer, confidentiality, nondisclosure, collaboration or other agreement, written or oral, not referenced In Section 4?
x NO ¨ YES (If Yes, please provide details)
7. What are the potential applications and/or sources of revenue from this Intellectual Property?
The STORM algorithm can be used to identify new peptide hormones, their receptors and regulatory proteins. These in tum can be used as targets for the development of new pharmacological therapeutics. STORM can also be used to design amino acid (ie peptide) based drugs. With respect to basic science STORM can be used to identify previously unknown paralogous peptide and proteins to understand the physiological regulation of a particular system and also help establish the phylogenetic interrelationships of species. Thus the STORM algorithm is likely to be of interest to scientists in both commercial and academic settings.
8. Warranty:
I/We, the Inventors/Contributors listed in Section 2(a), have read, understood and agree to all of the preceding and declare that all of the information provided in this disclosure is complete and correct. To the best of our knowledge, all persons who might legally make an ownership claim in this Intellectual Property are identified in Section 2(a) and 2(b).
| /s/ David Lovejoy |
Nov 14 | |
| Signature | Date | |
| Typed Name: | ||
| David Lovejoy |
For more information on University of Toronto Intellectual property policies, please call<PHONE_NUMBER> or access http://www.library.utoronto.ca/techtran/.
For information on commercialization processes and procedures please call the Innovations Foundation at<PHONE_NUMBER>.
Confidential Intellectual Property Disclosure (Inventions Policy)
January/03
Page 2 of 2
Exhibit 10.19(ii)
FIRST AMENDMENT TO TECHNOLOGY LICENSE AGREEMENT
THIS FIRST AMENDMENT TO TECHNOLOGY LICENSE AGREEMENT (the License Amendment) is made and entered into as of February 18, 2015 by and between THE GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO (UT), a corporation vested with the government, management and control of the University of Toronto by the University of Toronto Act, 1971 and having offices at Banting Institute, 100 College Street, Suite 413, Toronto, Ontario, Canada, M5G 1L5 and PROTAGENIC TIIERAPEUTICS, INC. a corporation incorporated under the laws of Delaware and having a principal place of business at 149 5th Avenue, Suite 500, New York, NY 10010, U.S.A. (Licensee).
BACKGROUND:
| A. | The Licensee and the University of Toronto Innovations Foundation (UTIF) entered into a technology license agreement effective July 21, 2005 (License Agreement). |
| B. | Effective May 1, 2006, UTIF ceased to operate its business and it transferred and assigned all of its business and assets to UT and the License Agreement continued under the same terms and conditions aside from UT replacing UTIF in said License Agreement. |
| C. | UT and Licensee entered into a sponsored research agreement dated December 14, 2004, as amended May 31, 2005; December 11, 2006; April 16, 2007; March 17, 2008; March 18, 2009; February 1, 2011; February 21, 2011; May 18, 2011; April 1, 2012; and April 1, 2013 and may enter into additional sponsored research agreements (collectively the Research Agreement). |
| D. | UT and Licensee wish for improvements (as defined in the License Agreement and listed under Schedule A hereto), created by David Lovejoy and/or other research participants under the Research Agreement while employed by UT, to be included in the License. |
| E. | UT and Licensee wish to amend the License Agreement in accordance with the conditions hereof. |
NOW THEREFORE, the Parties hereto agree to further amend and revise the License Agreement as follows:
All capitalized terms not defined herein shall have the same meaning ascribed to such terms as set out in the License Agreement.
| 1. | All references to the University of Toronto Innovations Foundation and UTIF are hereby deleted and replaced with The Governing Council of the University of Toronto and UT respectively. |
2. Section 1.1 -Definitions.
The definition of Improvements is hereby deleted in its entirety and replaced with the following:
Improvements means any and all improvements, variations, updates, modifications or enhancements to the Technology (including without limitation any related Intellectual Property Rights) which are developed under the terms of a research agreement dated December 14, 2004, as amended May 31, 2005; December 11, 2006; April 16, 2007; March 17, 2008; March 18, 2009; February 1, 2011; February 21, 2011; May 18, 2011; April 1, 2012; and April 1,2013, and under the terms of any other sponsored research agreement designated in same as being added by reference to Schedule B of this Agreement and this Agreement shall be deemed to be amended accordingly to incorporate all such sponsored research agreements as a Research Agreement by reference between Licensee and The Governing Council of the University of Toronto.
The definitions of Phase I End, Phase II End and Phase III End are hereby deleted in their entirety and replaced with the following:
Phase I End means approval by the FDA or other applicable regulatory authority to commence Phase II Clinical Trials of each Licensed Product as such trials are described in 21 C.F.R. 312.2 l(b);
Phase II End means approval by the FDA or other applicable regulatory authority to Commence Phase III Clinical Trials of each Licensed Product as such trials are described in 21 C.F.R.3 12.21(c);
Phase III End means Regulatory Approval of each Licensed Product;
The definition for University is hereby deleted in its entirety and replaced with the following:
University means The Governing Council of the University of Toronto.
3. Section 2.1(a) -Grant of License for Technology
Section 2.1 (a) is hereby deleted in its entirety and replaced with the following;
(a) an exclusive license within the Territory and within the Field of Use to develop, make, have made, use, sell, offer for sale and import the Technology and Licensed Products under all Owners and/or David Lovejoys and or UT rights, title and interest in the Technology and Licensed Products; and
4. Section 3.1 -Royalty
Section 3.1(f) is added as follow:
f) For clarity, Upfront Sub-License Fees shall exclude any and all research and development payments, reimbursements, loans and equity investments in the Company and payments made in respect of a collaboration agreement or acquisition agreement, whether such payments are for research milestones or otherwise, supply of product and similar arrangements.
5. Section 4.1 -Ownership
Section 4.1 is hereby deleted in its entirety and replaced with the following:
All Intellectual Property Rights in all aspects and parts of the Technology and Improvements shall be exclusively owned by the Owners, and/or David Lovejoy and/or the UT as the case may be and nothing herein shall serve to, or should be construed to transfer any Intellectual Property Rights whatsoever in the Technology or Improvements except to the extent that any such Intellectual Property Rights are developed solely by the Licensee (with or without a third party) in which case the Licensee shall own or co-developed with the Licensee, in which case the Licensee shall have co-ownership rights in same as applicable.
6. Section 4.3 -Patents and Patent Applications.
Section 4.3 (a) is hereby deleted in its entirety and replaced with the following:
| (a) | Licensee, in the name of the Owners, and/or David Lovejoy and/or UT (and as the case may be the Licensee if a joint developer) as the case may be, as assignee, shall file, prosecute and maintain the Patents. Licensee shall determine in which countries to pursue patent applications. In the event that Licensee elects not to continue prosecution in any country, UT may, at its sole discretion, file such patent or continue such prosecution in that country at its own expense. In such cases, any patents arising from such applications shall be excluded from the grant of rights under Section 2.1 herein for said country. |
Section 4.3 (e) is hereby deleted in its entirety and replaced with the following:
| (e) | Licensee undertakes to keep UT reasonably advised of the progress of prosecution and of any actions Licensee proposes to take or has taken in connection with the prosecution or maintenance of the Patents. Licensee shall provide UT with copies of correspondence and all actions issued by patent authorities and shall take into account any comments, remarks or suggestions UT may promptly provide to Licensee in writing at least ten (10) days prior to any due date established by Licensee for preparation of a response or amendment, and in all cases thirty (30) days prior to any patent office due date. |
7. Section 4.4 -Improvements
Section 4.4 is hereby amended by replacing the phrase at the third line, the name of the Owners, or David Lovejoy with the name of the Owners and/or David Lovejoy and/or UT (and, as the case may be) the Licensee if a joint developer)
8. Section 7 -Notices.
Section 7.3 (a) is hereby deleted and replaced with the following:
| (a) | In the case of a notice to Licensee: |
Protagenic Therapeutics, Inc.
149 5th Avenue,
Suite 500, New York, NY 10010
U.S.A.
Attention: Robert Ziroyan, PhD, MSc
E-mail<EMAIL_ADDRESS>With a copy to:
Gowlings Lafleur Henderson LLP
1 First Canadian Place
100 King Street West Suite 1600
Toronto, Ontario M5X 1G5
Canada
Attention: Anita Nador
E-mail<EMAIL_ADDRESS>Section 7.3 (b) is hereby deleted and replaced with the following:
| (b) | In the case of a notice to UT: |
Innovations and Partnerships Office
Banting Institute, 100 College Street, Suite 413
Toronto, Ontario M5G lL5
Canada
Attention: Jennifer Fraser
Director, Innovations
E-mail<EMAIL_ADDRESS>| 9. | Schedule A is hereby amended by including the additional Improvements (Confidential Intellectual Property Disclosures & related Patents and Patent Applications) under the Schedule. |
| 10. | Schedule B is hereby amended by incorporating by reference the 2012 and the 2013 Sponsored Research Agreements to the Schedule and any other Research Agreement designated in same as being added by reference to Schedule B of the License Agreement between Licensee and The Governing Council of the University of Toronto. |
| 11. | Except as set out herein, this License Amendment shall not amend or modify any other provision within the License Agreement. |
| 12. | This License Amendment shall be governed by the laws of the Province of Ontario and the federal laws of Canada applicable in the Province of Ontario |
IN WITNESS OF WHICH the Parties hereto have executed this First Amendment.
| PROTAGENIC THERAPEUTICS, INC. | THE GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO | |||||
| By: | /s/ Robert Ziroyan |
By: | /s/ Jennifer Fraser | |||
| Name: | Robert Ziroyan, PhD, MSc | Name | Jennifer Fraser | |||
| Title: | Chief Operating Officer, President | Title: | Director, Innovations |
SCHEDULE A
Additional Improvements
Project Ref: P1323
Copies of listed Invention Disclosures Attached
| S.No. |
Confidential |
Date of |
Named |
Title of Disclosure |
Date of | |||||
| 1. | 10002701 | Jan 16, 2014 | David Alan Lovejoy | Treatment of Insulin-Resistant Hyperglycemia by Teneurin C-Terminal Associated Peptide-1 | Feb 18, 2015 | |||||
| 2. | 10002574 | Mar 27, 2013 | David Alan Lovejoy; Chand Dhan | Treatment of Human male Infertility by Use of Teneurin C-Terminal Associated Peptide (TCAP- 1) Administration | March 3, 2015 |
| UNIVERSITY OF TORONTO | ||
| CONFIDENTIAL INTELLECTUAL PROPERTY DISCLOSURE | ||
| Banting Institute, Room 413 | ||
| 100 College Street, Toronto, ON M5G 1L5 | ||
| Tel:<PHONE_NUMBER> Fax:<PHONE_NUMBER> email<EMAIL_ADDRESS>|
1. Title of Invention: Treatment of insulin-resistant hyperglycemia by teneurin C-terminal associated peptide-1 administration
2. a) University of Toronto Inventors Individuals intimal to the University who have made an inventive contribution to this Invention i.e. faculty, students, postdocs, staff etc. Attach extra sheet if necessary:
| SURNAME, GIVEN NAMES |
UNIVERSITY PERSONNEL NO. |
DEPARTMENT (List any cross |
AFFILIATION |
EMAIL ADDRESS |
CONTACT INFORMATION (mailing address phone, fax) | |||||
| Lovejoy David Alan |
001012972 | Cell and Systems Biology |
Professor | David.lovejoy@ Utoronto.ca |
Tel: cell:<PHONE_NUMBER>, home:<PHONE_NUMBER>
Address: 149 Baker Street, Stouffville, Ontario, L4A 1K6 |
b) External Inventors Non-University of Toronto Individuals who have made an inventive contribution to the Invention. i.e. sponsor employees, academic collaborators, etc. List name, organization and e-mail address.
not applicable
| For Research Services use only: Date Received: JAN 16 2014 |
DISCLOSURE REFERENCE NO: 10002701 |
Version: 2011.09.08
| c) | Contributors Individuals Internal or external to the University who have not made an Inventive Contribution to this Invention but have made a valuable contribution to the development of the Invention. List name organization and e-mail address. |
Protagenic Therapeutics Inc provided the majority of the funding for this project
Contact: Dr. Robert Ziroyan<EMAIL_ADDRESS>3. Where did the work leading to this Invention take place? Please be specific
In vitro studies were conducted in rooms 304, 305 in Ramsay Wright Building at the University of Toronto. Animal studies were conducted in the Biosciences Support Facility central vivarium at Ramsay Wright. Hormone studies were performed under contract by Rules Based Medicine, a contract research organization (CRO)
4. Invention Description Please provide a description of this Invention for evaluation, highlighting its novel or patentable aspects. Attach a separate sheet if necessary.
TCAP-l is a 41 amino acid peptide derived from a natural protein (teneurin) found in the human reproductive organs and other tissues. It acts to regulate cell metabolism via a unique mechanism associated with activation of the dystroglycan complex leading to a signal transduction cascade to increase the number of glucose transporters in the cell membrane thereby increasing the transport of glucose into the cell. This action leads to significantly higher cellular energy in the form of increased cellular ATP levels. At the organismal level, single doses of TCAP-1 at 300 and 3000 pmoles significantly decrease blood glucose levels as long as one week later.
5. Have there been any prior disclosures (abstracts, presentations, publications) in respect of this Invention? List them and provide the date each disclosure occurred.
Chen C. Song L. de Lannoy L, Xu M, Crosier R, Lovejoy DA (November. 2013) Insulin independent glucose transport and enhanced neuron metabolism by Teneurin C-terminal Associated Peptide (TCAP)-l Society for Neuroscience. San Diego, USA
| 6. | a) How was the work leading to this Invention funded? (I.e. salaries, equipment used, supplies |
etc.)
| SPONSOR |
PROJECT TITLE |
RIS FUND # | ||
| Protagenic Therapeutics Inc | Evidence for the existence of TCAP receptors | 495550 |
b) Was the project/work leading to this Invention subject to any software licence, material transfer, confidentiality, non-disclosure, collaboration or other agreement, written or oral, not referenced in (a) above?
x NO ¨ YES (please provide details)
| 7. | Have any patent applications or other intellectual property protection been filled in respect of this invention? |
¨ NO x YES (please provide details)
| 1. | AUSTRALIA: September 2010. Patent Number: (May 2, 2003)<PHONE_NUMBER> Teneurin c-terminal associated peptides (tcap) and methods and uses thereof Inventors: LOVEJOY, David; CHEWPOY, R. Bradley; BARSYTE, Dalia; ROTZINGER, Susan. |
| 2. | UNITED STATES. August 26, 2011. Patent Number 10/510959. Teneurin c- terminal peptides (TCAP) and uses thereof LOVEJOY, David; CHEWPOY, R. Bradley; BARSYTE, Dalia; ROTZINGER, Susan. |
8. Warranty:
I/We the Inventors listed in Section 2(a), have read, understood and agree to all of the preceding, and declare that all of the Information provided in this disclosure is complete and correct. To the best of our knowledge, all persons who might legally make an ownership claim in this Invention are identified in Section 2(a) and 2(b).
| /s/ David A. Lovejoy | ||||||||
| Signature | Date: 01/14/2014 | Signature | ||||||
| Typed Name:
|
David A. Lovejoy | Typed Name: | ||||||
| Signature | Date | Signature | Date | |||||
| Typed Name: | Typed Name: |
| UNIVERSITY OF TORONTO | ||
| CONFIDENTIAL INTELLECTUAL PROPERTY DISCLOSURE | ||
| Banting Institute, Room 413 | ||
| 100 College Street, Toronto, ON M5G 1 L5 | ||
| Tel:<PHONE_NUMBER> Fax:<PHONE_NUMBER> email<EMAIL_ADDRESS>|
1. Title of Invention: Treatment of human male infertility by use of teneurin C-terminal associated peptide (TCAP)-1 administration
2. a) University of Toronto Inventors Individuals internal to the University who have made an inventive contribution to this Invention i.e. faculty, students, postdocs, staff etc. Attach extra sheet if necessary:
| SURNAME, GIVEN |
UNIVERSITY PERSONNEL NO. |
DEPARTMENT (List any cross |
AFFILIATION |
EMAIL ADDRESS |
CONTACT INFORMATION (mailing address phone, fax) | |||||
| Lovejoy David Alan |
001012972 | Cell and Systems Biology | Professor |<EMAIL_ADDRESS>| Tel:<PHONE_NUMBER> Dept of Cell of Systems Biology Ramsay Wright Bldg. 25 Harbord Street, University of Toronto | |||||
| Chand Dhan |
993001103 | Cell and Systems Biology |
Ph.D. Graduate | Dhan.chand @mail.utoronto.ca |
Tel:<PHONE_NUMBER> Dept. of Cell of Systems Biology Ramsay Wright Bldg. 25 Harbord street. University of Toronto |
b) External Inventors Non-University of Toronto individuals who have made an inventive contribution to the Invention, i.e. sponsor employees, academic collaborators, etc. List name, organization and email address.
not applicable
c) Contributors Individuals internal or external to the University who have not made an inventive contribution to this Invention but have made a valuable contribution to the development of the Invention. List name, organization and e-mail address.
Protagenic Therapeutics Inc provided the majority of the funding for this project
Contact: Dr. Robert Ziroyan<EMAIL_ADDRESS>| For Research Services use only: Date Received: Mar 27 2013 |
DISCLOSURE REFERENCE NO: 10002574 |
| 3. | Where did the work leading to this Invention take place? Please be specific. |
In vitro studies were conducted in rooms 304, 305 in Ramsay Wright Building at the University of Toronto. Animal studies were conducted in the Biosciences Support Facility central vivarium at Ramsay Wright. Hormone studies were performed under contract by Rules Based Medicine a contract research organization (CRO).
| 4. | Invention Description Please provide a description of this Invention for evaluation, highlighting its novel or patentable aspects. Attach a separate sheet if necessary. |
TCAP-l is a 41 amino acid peptide derived from a natural protein (teneurin) found in the human reproductive organs and other tissues. It acts to regulate cell metabolism via a unique mechanism associated with activation of the dystroglycan complex. In the male reproductive system the teneurin-dystroglycan complex is associated with regions of the testes and epididymis that play a role in spermatozoa formation, maturation and viability. In vivo studies indicate that synthetic TCAP-l modifies testicular and epididymal morphology increases testes size and increases testosterone production. These effects are consistent with increased activity of the reproductive system in mate mice. However because the peptide and hormone system is highly conserved in all mammals as well as vertebrates in general, these studies suggest that synthetic TCAP-l has potential to be used to treat some forms of male infertility in humans as well as other species.
| 5. | Have there been any prior disclosures (abstracts, presentations, publications) in respect of this invention? List them and provide the date each disclosure occurred. |
Chand D, Colacci M, Dixon K, Lovejoy DA. (2012). Gonadal characterization of the evolutionary conserved teneurin-dystroglycan system in mouse. 26th Conference of European Comparative Endocrinologists, Zurich, Switzerland (August 2012)
| 6. | a) How was the work reading to this Invention funded? (i.e. salaries, equipment used, supplies etc.) |
| SPONSOR |
PROJECT TITLE |
RIS FUND # | ||
| Protagenic Therapeutics Inc | Existence for the existence of TCAP Receptors in neurons |
457526 |
| b) | Was the project/work leading to this Invention subject to any software licence, material transfer, confidentiality, non-disclosure, collaboration or other agreement, written or oral, not referenced in (a) above ? |
x NO ¨ YES (please provide details)
| 7. | Have any patent applications or other Intellectual property protection been filed in respect of this invention? |
| ¨ NO x YES (please provide details) |
| 1. | AUSTRALIA: September 2010. Patent Number: (May 2,2003)<PHONE_NUMBER> Teneurin c-terminal associated peptides (tcap) and methods and uses thereof Inventors: LOVEJOY, David; CHEWPOY, R. Bradley; BARSYTE, Dalia; ROTZINGER, Susan |
| 2. | UNITED STATES. August 26, 2011. Patent Number 10/510959. Teneurin C-terminal peptides (TCAP) and uses thereof. LOVEJOY, David; CBEWPOY, R. Bradley; BARSYTE, Dalia; ROTZINGER, Susan. |
| 8. | Warranty: |
I/We. the Inventors listed in Section 2(a) , have read, understood and agree to all of the preceding, and declare that all of the Information provided in this disclosure is complete and correct. To the best of our knowledge, all persons who might legally make an ownership claim in this Invention are identified in Section 2(a) and 2(b)
| /s/ David A. Lovejoy | /s/ Dan S. Chand | |||||||
| Signature | Date: 03/20/2013 | Signature | Date: 03/20/2013 | |||||
| Typed Name:
|
David A. Lovejoy | Typed Name: | Dhan S. Chand | |||||
| Signature | Date | Signature | Date | |||||
| Typed Name: | Typed Name: |
SCHEDULE A (Continued)
Status Listing of Patent Applications filed for the Improvements
| TENEURIN C- TERMINAL ASSOCIATED PEPTIDES (TCAP) AND METHODS AND USES THEREOF |
| Inventors: LOVEJOY, David; CHEWPOY, R. Bradley; BARSYTE, Dalia; ROTZINGER, Susan |
| COUNTRY |
REFERENCE# | TYPE | FILED | SERIAL # | ISSUED | PATENT # | STATUS | |||||||||
| UNITED STATES |
T8476262USP1<PHONE_NUMBER>25) |
OTH | 05/03/2002 | 60/377,231 | EXPIRED | |||||||||||
| UNITED STATES |
T8476262USP2<PHONE_NUMBER>27) |
OTH | 11/06/2002 | 60/424,016 | EXPIRED | |||||||||||
| WIPO | T8476262WO<PHONE_NUMBER>35) |
CEQ | 05/02/2003 | PCT/ CA03/00622 |
ENTERED NATIONAL PHASE | |||||||||||
| AUSTRALIA | T8476262AU<PHONE_NUMBER>31) |
DCA | 05/02/2003 |<PHONE_NUMBER> | 09/23/2011 |<PHONE_NUMBER> | ISSUED | |||||||||
| CANADA | T8476262CA<PHONE_NUMBER>29) |
DCA | 05/02/2003 | 2,482,810 | 06/10/2014 | 2,482,810 | ALLOWED | |||||||||
| EUROPEAN PATENT |
T8476262EP<PHONE_NUMBER>33) |
DCA | 05/02/2003 | 03717086.7 | 03/12/2014 | 1499635 | GRANTED | |||||||||
| COMMENTS: |
Validated in France, Germany and Great Britain Opposition period is over; no opposition(s) filed | |||||||||||||||
| JAPAN | T8476262JP<PHONE_NUMBER>34) |
DCA | 05/02/2003 | 2004-501444 | ABANDONED | |||||||||||
| UNITED STATES |
T8476262US<PHONE_NUMBER>30) |
DCA | 11/01/2004 | 10/510,959 | 01/03/2012 | 8,088,889 | ISSUED | |||||||||
| UNITED STATES |
T8476262USCON<PHONE_NUMBER>01) |
CON | 11/09/2011 | 13/292,849 | PENDING |
A METHOD FOR INHIBITING NEURAL CELL DEATH
Inventor: LOVEJOY, David
| COUNTRY |
REFERENCE# |
TYPE |
FILED |
SERIAL # |
ISSUED |
PATENT # |
STATUS | |||||||
| UNITED STATES |
T8476261USP<PHONE_NUMBER>51) |
NEW | 02/15/2006 | 60/773,309 | EXPIRED | |||||||||
| UNITED STATES |
T8476261US<PHONE_NUMBER>36) |
Non- provisional |
02/15/2007 | 11/706,376 | ABANDONED | |||||||||
| COMMENTS: This application was abandoned in lieu of filing a Continuation Application |
| UNITED STATES |
T8476261USCON<PHONE_NUMBER>30) |
CON | 08/03/2011 | 13/197,575 | ABANDONED | |||||||||
| COMMENTS: July 1, 2014 INSTRUCTIONS TO ABANDON APPLICATION RECEIVED | ||||||||||||||
| COMMENTS: This application is a Continuation of US application No. 11/706,376 |
A METHOD FOR REGULATING NEURITE GROWTH
Inventor: LOVEJOY, David
| COUNTRY |
REFERENCE# |
TYPE |
FILED |
SERIAL # |
ISSUED |
PATENT # |
STATUS | |||||||
| UNITED STATES |
T8476288USP<PHONE_NUMBER>46) |
NEW | 03/21/2006 | 60/783,821 | EXPIRED |
METHOD FOR MODULATING GLUCOSE TRANSPORT USING TENEURIN C-TERMINAL ASSOCIATE PEPTIDE (TCAP)
Inventor: LOVEJOY, David; CHEN, Yani
| COUNTRY |
REFERENCE# |
TYPE | FILED | SERIAL # | ISSUED | PATENT # | STATUS | |||||||
| UNITED STATES |
T8476302USP | Provisional | 07/18/2014 | 62/026,346 | PENDING |
TENEURIN C-TERMINAL ASSOCIATED PEPTIDE (TCAP) AS AN ANTAGONIST OF LATROTOXIN
Inventor: LOVEJOY, David A; DAQUILA, Andrea L.
| COUNTRY |
REFERENCE# |
TYPE | FILED | SERIAL # | ISSUED | PATENT # | STATUS | |||||||
| UNITED STATES |
T8476314USP | Provisional | NOT FILED |
SCHEDULE B
Additional Research Agreement (s)
Copies of listed Sponsored Research Agreements Incorporated by Reference
Principal Investigator: David Alan Lovejoy
| S.No. |
Research Agreement |
Effective Date |
End Date |
Project Title |
Fund Number | |||||
| 1. | Sponsored Research Agreement |
Apr 1, 2012 | March 31, 2013 | Evidence for existence of TCAP receptors in neurons | 495550 | |||||
| 2. | Sponsored Research Agreement |
Apr 1, 2013 | March 31, 2014 | Teneurin C-terminal Associated Peptide (TCAP)-mediated stress attenuation in vertebrates: Establishing the role of organismal and intracellular energy and glucose regulation and metabolism | 495550 |
Exhibit 10.20(i)
SPONSORED RESEARCH AGREEMENT
This agreement (the Agreement) is made effective 1 April 2014 (the Effective Date).
BETWEEN:
THE GOVERNING COUNCIL OF THE UNIVERSITY OF TORONTO
(the University)
-and-
PROTAGENIC THERAPEUTICS CANADA (2006), INC,
PROTAGENIC THERAPEUTICS INC.
(the Sponsor)
(Individually a Party and collectively the Parties)
WHEREAS the parties have entered into a Technology License Agreement effective July 21, 2005, as amended, (collectively, the License Agreement)
AND WHEREAS the Parties under said License Agreement wish to undertake a research project entitled Teneurin C-terminal Associated Peptide (TCAP)-mediated stress attenuation in vertebrates: Establishing the role of organismal and intracellular energy and glucose regulation and metabolism. as described in the attached Appendix A and add this as an additional Research Agreement under Schedule B of the License Agreement (the Project);
AND WHEREAS the Sponsor wishes to support the Project;
NOW THEREFORE the Parties hereby agree as follows:
| 1.0 | THE PROJECT |
| 1.1 | Project. The University will perform the Project as described in the attached Appendix A which University has determined is in accordance with University policies and procedures. The Project is consistent with the Universitys primary mission, which is education and advancement of knowledge. The manner of performance of the Project shall be determined solely by the Principal Investigator, after consultation with the Sponsor and subject to substantial compliance in all respects with Appendix A and all other provisions of this Agreement, as may be amended from time to time and applicable laws and regulations, including without limitation those governing the use of animals in research. University will cause diligent efforts to be used to perform the Project in a timely manner and in accordance with appropriate scientific standards. Neither Party makes any warranties or representations regarding its ability to achieve, nor shall it be bound to accomplish, any particular research objective or results. |
The Governing Council of the University of Toronto
Protagenic Therapeutics, Inc.
Page 1
| 1.2 | Principal Investigator. The Project will be performed under the supervision and direction of Prof. David Lovejoy of the Department of Cell and Systems Biology (the Principal Investigator), together with such additional personnel as the Parties may assign. If Dr. Lovejoy becomes unavailable at any time during the Project, the University may nominate a replacement individual as Principal Investigator, such nomination to be made within fourteen (14) days of the date on which Dr. Lovejoy becomes unavailable. If the Sponsor, for any reason, does not accept the nominated replacement Principal Investigator or a replacement Principal Investigator is not nominated by the University, as Sponsors sole discretion, the Research Program may be amended to reflect a reduced scope of work for the Project, or the Agreement may be terminated by the Sponsor as set forth in Article 5.2. |
| 1.3 | Budget. In consideration of the University carrying out the Project, the Sponsor will pay the University the sum of CA$ 75,475 (currency: Canadian Dollars) in compensation for the direct and indirect costs of the Project, all generally in accordance with the budget contained in the attached Appendix B. |
| 1.4 | Payment. Subject to Article 5.2, the University shall issue invoices and the Sponsor shall pay the sum set out in Article 1.3 to the University in accordance with the payment schedule in the attached Appendix B. |
| 1.5 | Equipment. The University will own any equipment or material purchased by the University under the Project. |
| 1.6 | Report. The University will share all data, results research work conclusions and recommendations arising from the performance of the Project (Research Results) with Sponsor. The University will provide reports of Research Results to Sponsor at least on a calendar quarter basis, or as may be reasonably requested by Sponsor, and will include in such reports a meaningful summary of the research accomplished in comparison to the Project description. The University, through the Principal investigator, will participate in discussions and/or meetings with Sponsor with respect to Research Results and the progress of the Project as may be reasonably requested by the Sponsor. The University will submit a final report describing the results of the Project to the Sponsor within sixty (60) days of completion of the Project. |
| 1.7 | Undertakings. |
| a. | The University will ensure that, prior to commencement of the Project the Principal Investigator and any replacement shall execute the Principal Investigators Undertaking (PIU) attached as Appendix C; any additional personnel, including without limitation, each additional investigator involved in the Project shall execute a Confidential Information and Intellectual Property Agreement (CIIP) attached as Appendix D. |
| b. | The University and Principal Investigator shall ensure that all work performed by such personnel on the Project is in compliance with the terms of this Agreement. |
| c. | In order for University to fulfil its obligations under this Agreement, including without limitation under Section 2.0 of this Agreement, University shall ensure Investigator and additional personnel (including any and all inventors), as applicable, are obligated to assign and do irrevocably assign any and all of their rights in the Foreground Intellectual Property to the University, including the right to make any claims of priority therefrom |
The Governing Council of the University of Toronto
Protagenic Therapeutics, Inc.
Page 2
| 2.0 | INTELLECTUAL PROPERTY |
| 2.1 | Definitions. In this Agreement, |
| a. | Background Intellectual Property means Intellectual Property of a Party that is: |
| i. | proprietary to that Party and was conceived, created, or developed prior to, or independent of, any research performed pursuant to or related to this Agreement or a Project hereunder; and |
| ii. | necessary for the performance of a Project. |
| b. | Foreground Intellectual Property means Intellectual Property that is discovered, created or reduced to practice in the performance of a Project. |
| c. | Intellectual Property (or IP) means all intellectual property, including technical information, know-how, models, drawings, specifications, prototypes, inventions and software. |
| d. | University Foreground Intellectual Property means Intellectual Property that is discovered, created or reduced to practice by University personnel in the performance of a Project. |
| e. | University personnel shall include but not necessarily limited to the Principal Investigator (PI) and University employees, subcontractors, consultants, technicians, students, post-docs and visiting scientists. Other than the Sponsor or by written consent of the Sponsor, the University shall not have anyone other than University personnel work on the Project. |
| 2.2 | Ownership |
| a. | Background Intellectual Property of a Party shall remain the exclusive property of such Party. |
| b. | The University shall own all University Foreground Intellectual Property. |
| c. | Subject to all of the terms and conditions of this Agreement and the License Agreement (including section 7.2 of the License Agreement) and the agreement of any assignee to be bound hereby in writing, the University may assign its interest in University Foreground Intellectual Property according to the Universitys applicable policies and procedures upon prior notice and prior written consent by the Sponsor, such consent not to be unreasonably withheld. |
| 2.3 | Disclosure of Inventions: The Principal Investigator will disclose any University Foreground Intellectual Property to the University in accordance with the Universitys Inventions Policy, and such disclosure will be communicated to the Sponsor promptly and in reasonably sufficient detail to permit assessment by Sponsor. Universitys obligation under this Article 2.3 will not be satisfied by submission of any report as required under Article 1.6 of this Agreement. |
The Governing Council of the University of Toronto
Protagenic Therapeutics, Inc.
Page 3
| 2.4 | Sponsors Rights |
| a. | Option: Provided that the Sponsor is not in breach of its obligations under this Agreement, the Sponsor will have the option to obtain at its preference, either an exclusive or non-exclusive licence to use Universitys interest in University Foreground Intellectual Property in accordance with the terms of the License Agreement (the Option). |
| b. | Option Period: The Sponsor must indicate its intention to exercise the Option by notifying the University in writing within one hundred eighty (180) days of disclosure of the University Foreground Intellectual Property to the Sponsor (the Option Period), failing which the University or its assignee(s) may offer licenses to the University Foreground Intellectual Property to third parties without further obligation to Sponsor. Unless otherwise agreed to in writing by the Parties, the University shall be under no obligation to file, prosecute or maintain patents related to the University Foreground Intellectual Property during the Option Period. For clarity, the University shall not disclose any of the University Foreground Intellectual Property to third parties during the Option Period. In the event Sponsor exercises the Option, University will grant to Sponsor the non-exclusive right to use University Background Intellectual Property to the extent necessary to practice the University Foreground Intellectual Property as provided in the License Agreement. |
| c. | Representations and Warranties: Sponsor acknowledges and agrees that under the terms of the License Agreement: (i) the University Foreground Intellectual Property will be supplied and licensed to the Sponsor on an as is basis; (ii) the University Foreground Intellectual Property will exclude representations and warranties as to the patentability, validity, scope or enforceability of the University Foreground Intellectual Property; and (iii) the University Foreground Intellectual Property will exclude representations and warranties that any use of the University Foreground Intellectual Property will be free from infringement of intellectual property rights of any third party. Notwithstanding the above, nothing in this Agreement is intended to alter or amend the terms of the License Agreement except in respect of the addition of University Foreground Intellectual Property subject to exercise of the Option. |
| 2.5 | Research and Teaching. Notwithstanding anything in this Agreement or any resulting license, the University will retain the right to use Universitys interests in all University Foreground Intellectual Property for non-commercial research, educational and administrative purposes, without cost and in perpetuity. |
| 2.6 | Similar Research. Nothing in this Agreement will be construed to limit the freedom of the University or of its researchers from engaging in similar research made under other agreements with parties other than the Sponsor as long as it does not conflict with or supersede the rights of the prior rights of the Sponsor under this Agreement or the License Agreement. |
The Governing Council of the University of Toronto
Protagenic Therapeutics, Inc.
Page 4
| 3.0 | CONFIDENTIAL INFORMATION |
| 3.1 | Confidential Information. The Parties may disclose confidential information one to another to facilitate performance of this Agreement. Such information will be identified as confidential in writing at the time of its transmittal, or so reduced to writing within fifteen (15) days thereafter (Confidential Information), and will be safeguarded and not disclosed to third parties by the receiving Party. Confidential Information will not include information that: |
| a. | is already known to the Party to which it is disclosed; |
| b. | is or becomes part of the public domain without breach of this Agreement; |
| c. | is obtained from third parties which have no obligations to keep confidential to the Parties to this Agreement; |
| d. | was independently developed by the receiving Party without the use of, reference to or reliance upon any of the Confidential Information of the disclosing Party. |
| 3.2 | Notwithstanding anything contained herein, each Party may disclose Confidential Information to its officers, employees, consultants, agents, and students on a need-to-know basis to facilitate performance of the Project, provided that such persons agree to be bound by terms at least as restrictive as those contained herein. |
| 4.0 | PUBLICATION OF RESEARCH RESULTS |
| 4.1 | Review. The University will provide a copy of any proposed publication of Project research results (a Publication) to the Sponsor for its review at least thirty (30) days before submission for publication or disclosure. Upon the Sponsors written request received within twenty (20) days of the Sponsors receipt of the Publication or intended disclosure, the University will, at the Sponsors option: |
| a. | delete identifiable references to any Confidential Information provided by the Sponsor from the proposed Publication or intended disclosure; |
| b. | if the Sponsor has exercised the Option, delay publication of the Publication up to sixty (60) additional days to enable the Sponsor to file; in the name of the Intellectual Property owner or its assignee(s), patent application(s) for any Intellectual Property that would be publicly disclosed in the Publication. |
| 4.2 | Academic Progression: Except in respect of Article 4.1(a), nothing in Article 4.1 will impose restrictions on the content or handling, for academic purposes, of the thesis of any Project participant. |
| 4.3 | Disclosure of Research Results. Subject to Article 4.1, the University reserves on behalf of itself, the Principal Investigator and all other Project participants the right to disseminate information or otherwise publish the research results arising in performance of the Project. The Sponsors support of the Project will be acknowledged in all such publications. |
The Governing Council of the University of Toronto
Protagenic Therapeutics, Inc.
Page 5
| 5.0 | TERM AND TERMINATION |
| 5.1 | Term. This Agreement will enter into force as of the Effective Date and will terminate on 31 March 2015 (Term) unless sooner terminated in accordance with Article 5.2 below, or upon the written agreement of the Parties. |
| 5.2 | Termination. This agreement may be terminated as follows: |
| a) | Sponsor may terminate this Agreement upon sixty (60) days written notice to University. In the event of termination, the University will be entitled to credit for work performed hereunder before termination including the Universitys non-cancellable costs incurred by University prior to the date of notice of termination, and the Sponsor will be entitled to a return of the balance of any advance payment; |
| b) | by the Sponsor upon giving sixty (60) days written notice to the University if, in the reasonable judgment of the Company, the research program is no longer technically or commercially feasible; |
| c) | written notice to the University if, at any time during the Term or any extension thereof, the parties are unable to agree on the terms of an amendment to the Research Program; |
| d) | by the Sponsor immediately upon giving written notice to the University if (i) the Sponsor does not accept the replacement Principal Investigator nominated by the University or (ii) if no replacement is nominated within (14) days of the date on which Dr. Lovejoy become unavailable; |
| e) | by the Sponsor upon giving thirty (30) days written notice to the University if a research milestone has not achieved within the time period specified in the Research Project; or, |
| f) | by University or the Sponsor upon giving thirty (30) days written notice to the other if University is in default of fulfilling any of its material obligations under this Agreement and such default has not been cured within such thirty (30) days notice period. |
| 5.3 | Effect of Termination. The provisions of Articles 1.4, 1.5, 2.0, 3.0, 4.0, 5.0, 6.0 and 7.0 will survive termination or expiration of this Agreement in accordance with their terms. |
| 6.0 | LIABILITY AND INDEMNITY |
| 6.1 | Limitation of Liability. Neither Party will be liable for any delays in the performance of its obligations under this Agreement resulting from circumstances or causes beyond its reasonable control, and in no case will the Parties be liable for loss of business or profit or other indirect or consequential damages. |
| 6.2 | Indemnity. The University will indemnify and save harmless the Sponsor against all costs, suits or claims on account of injuries (including death) to persons participating in the Project or to damage to University property caused by the wilful or negligent act or omission of personnel of University during the performance of this Agreement. The Sponsor will |
The Governing Council of the University of Toronto
Protagenic Therapeutics, Inc.
Page 6
| indemnify and save harmless the University and its employees, students and agents against all costs, suits or claims on account of injuries (including death) to persons participating in the Project or to damage to property caused by agents or personnel of the Sponsor during the performance of this Agreement or resulting from the use by the Sponsor or its affiliates, its customers or licensees of any deliverable or intellectual property developed under this Agreement. |
| 7.0 | MISCELLANEOUS |
| 7.1 | Use of Names. Neither Party will use the name of the other Party, or of any member of the other Partys personnel, in any advertising or publicity without the prior written approval of the other Partys authorized representative. However, both Parties may make the following information a matter of public record: name of Principal Investigator; Principal Investigators department; Universitys name; Sponsors name; Project title; Project duration; and, contract value. |
| 7.2 | Independent Parties. The Parties are independent parties and nothing in this Agreement will constitute either Party as the employer, principal or partner of or joint venturer with the other Party. Neither Party has any authority to assume or create any obligation or liability, either express or implied, on behalf of the other Party. |
| 7.3 | Notices. Notices under this Agreement will be sent to the Parties as follows or to such other person as a Party may designate in writing: |
For Technical and Scientific Matters:
| To University: |
To Sponsor: |
|||||
| Name: | Prof. David Lovejoy | Robert Ziroyan | Garo Armen | |||
| Department: | Dept. of Cell and Systems Biology | Protagenic Therapeutics Canada(2006), Inc. | Protagenic Therapeutics Inc. | |||
| Address: | 25 Harbord Street | 22 Elkhorn Drive, Suite 424 | 149 5th Avenue, Suite 500 | |||
| City, Province/State: | Toronto, ON | Toronto, ON | New York, NY | |||
| Postal/Zip Code, Country: | M5S 3G5 | M2K 1J4 | 10010 | |||
| Tel: |<PHONE_NUMBER> |<PHONE_NUMBER> |<PHONE_NUMBER> | |||
| Email: |<EMAIL_ADDRESS>|<EMAIL_ADDRESS>|<EMAIL_ADDRESS>|
The Governing Council of the University of Toronto
Protagenic Therapeutics, Inc.
Page 7
For Legal and Administrative Matters:
| To University: |
To Sponsor: | |||
| Name: | Colleen Burke | Robert Ziroyan | ||
| Department: | Innovations & Partnerships Office (IPO), University of Toronto | Protagenic Therapeutics Canada (2006), Inc. | ||
| Address: | Banting Institute 100 College Street, Suite 413 |
22 Elkhorn Drive, Suite 424 | ||
| City, Province/State: | Toronto, ON | Toronto, ON | ||
| Postal/Zip Code, Country: | M5G 1L5 Canada | M2K 1J4 | ||
| Tel: |<PHONE_NUMBER> |<PHONE_NUMBER> | ||
| Email: |<EMAIL_ADDRESS>|<EMAIL_ADDRESS>|
For Financial Matters:
| To University: |
To Sponsor: |
|||||
| Name: | Yolanda Buenaflor | Robert Ziroyan | Garo Armen | |||
| Department: | Research Oversight & Compliance Office (ROCO), University of Toronto |
Protagenic Therapeutics Canada (2006), Inc. | Protagenic Therapeutics Inc. | |||
| Address: | McMurrich Building, F2 12 Queens Park Crescent W. |
22 Elkhom Drive, Suite 424 | 149 5th Avenue, Suite 500 | |||
| City, Province/State: | Toronto, ON | Toronto, ON | New York, NY | |||
| Postal/Zip Code, Country: | M5S 1S8 Canada | M2K 1J4 | 10010 | |||
| Tel: |<PHONE_NUMBER> |<PHONE_NUMBER> |<PHONE_NUMBER> | |||
| Email: |<EMAIL_ADDRESS>|<EMAIL_ADDRESS>|