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(b) AbbVie may terminate this Agreement, in its entirety or on a country-by-country basis, for any or no reason, upon one hundred and eighty (180) days' prior written notice to Calibr. |
(c) AbbVie may terminate this Agreement pursuant to Section 10.8. |
12.2.3 Termination for Insolvency. In the event that either Party (or, if applicable, a parent of such Party) (a) files for protection under bankruptcy or insolvency laws, (b) makes an assignment for the benefit of creditors, (c) appoints or suffers appointment of a receiver or trustee over substantially all of its pro... |
12.2.4 Termination for Patent Challenge. If, during the Term, AbbVie or any of its Affiliates or Sublicensees of Calibr Patents under this Agreement: (a) commences, knowingly assists, induces, knowingly facilitates or otherwise voluntarily participates in any action or proceeding (including any administrative proceedin... |
12.3 Rights in Bankruptcy. All rights and licenses granted under or pursuant to this Agreement by AbbVie or Calibr are and shall otherwise be deemed to be, for purposes of Section 365(n) of the U.S. Bankruptcy Code or any analogous provisions in any other country or jurisdiction, licenses of rights to "intellectual pro... |
12.4 Consequences of Termination. |
12.4.1 Consequences of Termination. If this Agreement is terminated in its entirety, or with respect to a country (such country(ies), each a "Terminated Territory") or a Licensed Product(s) (such Licensed Product(s), each a "Terminated Product"), then the following shall apply: |
(a) All rights and licenses granted by Calibr to AbbVie under Section 4.1.1, Section 4.1.2 (if AbbVie exercises the CD19 License Option) and Section 4.1.3 shall immediately terminate and all rights and licenses granted by AbbVie to Calibr under Section 4.3 shall immediately terminate (i) in the case where this Agreemen... |
(b) If this Agreement is terminated by AbbVie pursuant to Section 12.2.2(b) or by Calibr pursuant to Section 12.2.1, Section 12.2.3, or Section 12.2.4, AbbVie shall, with respect to each Licensed Product (or Terminated Product, if applicable) that is a Reversion Product, (i) assign to Calibr any Program Product Inventi... |
(c) If this Agreement is terminated by AbbVie pursuant to Section 12.2.2(b), then on a Reversion-Product-by-Reversion Product and Terminated Territory-by-Terminated Territory basis for a period of ten (10) years following the date of the First Commercial Sale of such Reversion Product, Calibr shall pay to AbbVie a roya... |
(d) If Calibr requests, AbbVie shall reasonably cooperate with Calibr to facilitate orderly transition to Calibr or its designee of the Development and Commercialization of Reversion Products, including by, to the extent permitted under the relevant agreement at the time of termination, assigning to Calibr any agreemen... |
(e) AbbVie shall transfer to Calibr or Calibr's designee copies of all data, reports, records and materials, including all non-clinical and clinical data solely relating to any Reversion Products and all adverse event or other safety data, in AbbVie's (or its Affiliate's) possession and Control to the extent that such ... |
(f) Unless AbbVie terminated this Agreement pursuant to Section 12.2.2(a), AbbVie and Calibr shall promptly negotiate in good faith the terms and conditions of a written transition agreement pursuant to which, at Calibr's cost and expense (or, with respect to clause (i) and (ii) below, at AbbVie's cost and expense if t... |
(g) If AbbVie, any of its Affiliates or any Sublicensee is Manufacturing a Reversion Product, then, at Calibr's request, AbbVie shall supply such Reversion Product to Calibr in such form, and such quantities, as AbbVie or such Affiliate or Sublicensee is then Manufacturing such Reversion Product for worldwide use or us... |
(h) AbbVie shall, upon Calibr's written request, transfer to Calibr any inventory of Reversion Products for worldwide use or use in the Terminated Territory, as applicable, owned or under AbbVie's or any of its Affiliates or Sublicensees control (i.e., being stored at a warehouse) as of the termination date at the actu... |
(i) If, at the time of such termination, AbbVie or any of its Affiliates are conducting clinical trials for a Reversion Product, (A) if this Agreement is terminated with respect to the entire Territory anywhere in the world or (B) if this Agreement is terminated with respect to a Terminated Territory, that is reasonabl... |
12.4.2 Additional Calibr Rights. |
(a) Additional Reversion Data. Upon any termination of this Agreement, in addition to those provisions surviving under Section 12.7 and without limiting Section 12.4.1, AbbVie shall, within forty-five (45) days following the effective date of termination provide a high level summary to Calibr of any AbbVie IP or other ... |
(b) Calibr Option. Calibr shall have the right for ninety (90) days following the delivery of the Reversion Data from AbbVie to Calibr to elect to negotiate with AbbVie in good faith, for a period not to exceed one hundred and eighty (180) days (or such longer term as may be mutually agreed by the Parties), commerciall... |
(c) Option Limitations. It is understood and agreed that, without limiting Section 12.4.1, AbbVie's election to grant or not grant Calibr any rights under the AbbVie IP pursuant to the negotiations set forth in this Section 12.4.2, including the scope or terms thereof, are solely at AbbVie's discretion and the terms of... |
12.5 AbbVie Rights in Lieu of Termination. If AbbVie has the right to terminate this Agreement pursuant to Section 12.2.1 (including as may be finally determined in accordance with Section 13.5), then within ninety (90) days following the expiration of the relevant cure period AbbVie may, by written notice to Calibr, a... |
12.5.1 AbbVie may assume all activities previously performed by Calibr under this Agreement as they relate to (a) if the breach affects one (1) or more Target Programs, the Licensed Product(s) within such Target Program(s) and (b) if the breach is of a general nature, all Licensed Products (such Licensed Product(s) in ... |
12.5.2 the financial provisions set forth in Article 7 will continue to apply with respect to AbbVie's payment obligations hereunder following AbbVie's delivery of its notice to exercise its alternative remedy pursuant to this Section 12.5 provided, that (a) the Milestone Payments payable by AbbVie to Calibr pursuant t... |
12.5.3 Calibr's obligation to pay for any AbbVie Development Costs pursuant to Section 3.3.4, if applicable, shall terminate with respect to any AbbVie Development Costs incurred after the date of such notice and Calibr shall not have the right to exercise any Cost-Sharing Option; |
12.5.4 (a) if the Impacted Products are all the Licensed Products under this Agreement, AbbVie's diligence obligations under Section 5.2 shall terminate and (b) if the Impacted Products are Directed to an Included Existing Target, AbbVie's diligence obligations under Section 2.1.6(e) with respect to such Included Exist... |
12.5.5 all other provisions of this Agreement shall remain in full force and effect without change. |
12.6 Remedies. Except as otherwise expressly provided herein, termination of this Agreement in accordance with the provisions hereof shall not limit remedies that may otherwise be available in law or equity. |
12.7 Accrued Rights; Surviving Obligations. |
12.7.1 Survival. Termination or expiration of this Agreement for any reason will be without prejudice to any rights that will have accrued to the benefit of a Party prior to such termination or expiration; provided, that except as set forth in this Section 12.7.1, in no event shall Calibr accrue any rights to, and AbbV... |
12.7.2 Wind-Down. Notwithstanding the termination of AbbVie's licenses and other rights under this Agreement, AbbVie will have the right (except in the case of termination by Calibr pursuant to Section 12.2.1, Section 12.2.3 or Section 12.2.4 or by AbbVie pursuant to Section 12.2.2(b), where such right shall require Ca... |
ARTICLE 13 MISCELLANEOUS |
13.1 Force Majeure. Neither Party shall be held liable or responsible to the other Party or be deemed to have defaulted under or breached this Agreement for failure or delay in fulfilling or performing any term of this Agreement when such failure or delay is caused by or results from events beyond the reasonable contro... |
13.2 Export Control. This Agreement is made subject to any restrictions concerning the export of products or technical information from the United States or other countries that may be imposed on the Parties from time to time. Each Party shall not, and shall cause its Affiliates not to, export, directly or indirectly, ... |
13.3 Assignment. |
13.3.1 Neither Party may assign its rights or, except as provided in Section 2.6.2 or Section 5.4 or Section 13.19, delegate its obligations under this Agreement, whether by operation of law or otherwise, in whole or in part without the prior written consent of the other Party, which consent shall not be unreasonably c... |
13.3.2 AbbVie and Calibr each agrees that, notwithstanding any provision of this Agreement to the contrary, in the event that a Third Party merges or consolidates with or acquires a Party or an Affiliate of a Party, or a Party or an Affiliate of a Party transfers to a Third Party all or substantially all of its assets ... |
13.4 Severability. If any provision of this Agreement is held to be illegal, invalid or unenforceable under any present or future law and if the rights or obligations of either Party under this Agreement will not be materially and adversely affected thereby, (a) such provision shall be fully severable, (b) this Agreeme... |
13.5 Dispute Resolution. Except as otherwise provided in Section 2.1.6, Section 6.4, Section 7.16.2, Section 13.10 or Section 13.11, any dispute arises between the Parties in connection with or relating to this Agreement or any document or instrument delivered in connection herewith (a "Dispute"), shall be resolved pur... |
13.5.1 General. All Disputes shall first be referred to the Senior Officers, who shall confer in good faith on the resolution thereof. Any final decision mutually agreed to by the Senior Officers in writing shall be conclusive and binding on the Parties. If the Senior Officers are not able to agree on the resolution of... |
13.5.2 Intellectual Property Disputes. If a Dispute arises with respect the validity, scope, enforceability, inventorship or ownership of any Patent, Trademark or other intellectual property rights, and such Dispute cannot be resolved in accordance with Section 13.5.1, unless otherwise agreed by the Parties in writing,... |
13.5.3 Adverse Ruling. Any determination pursuant to this Section 13.5 that a Party is in material breach of its material obligations hereunder shall specify a (nonexclusive) set of actions to be taken to cure such material breach, if feasible. |
13.5.4 Interim Relief. Notwithstanding anything herein to the contrary, nothing in this Section 13.5 shall preclude either Party from seeking interim or provisional relief, including a temporary restraining order, preliminary injunction or other interim equitable relief concerning a Dispute, if necessary to protect the... |
13.6 Governing Law. This Agreement or the performance, enforcement, breach or termination hereof shall be interpreted, governed by and construed in accordance with the laws of the State of New York, United States, excluding any conflicts or choice of law rule or principle that might otherwise refer construction or inte... |
13.7 Notices. |
13.7.1 Notice Requirements. Any notice, request, demand, waiver, consent, approval or other communication permitted or required under this Agreement shall be in writing, shall refer specifically to this Agreement and shall be deemed given only if delivered by hand or sent by facsimile transmission (with transmission co... |
13.7.2 Address for Notice. |
If to AbbVie, to: AbbVie Global Enterprises Ltd. 4th Floor, Washington House 16 Church Street Hamilton HM 11 Bermuda with a copy (which shall not constitute notice) to: AbbVie Inc. 1 North Waukegan Road North Chicago, Illinois 60064 United States Attention: Executive Vice President, External Affairs, General Counsel an... |
13.8 Entire Agreement; Amendments. This Agreement, together with the Schedules attached hereto, sets forth and constitutes the entire agreement and understanding between the Parties with respect to the subject matter hereof and, subject to Section 13.19, supersedes all prior agreements, understandings, promises and rep... |
13.9 English Language. This Agreement shall be written and executed in, and all other communications under or in connection with this Agreement shall be in, the English language. Any translation into any other language shall not be an official version thereof and in the event of any conflict in interpretation between t... |
13.10 Equitable Relief. Each Party acknowledges and agrees that the restrictions and obligations set forth in Section 4.7, Section 8.1, and Article 9 are reasonable and necessary to protect the legitimate interests of the other Party and that such other Party would not have entered into this Agreement in the absence of... |
13.11 Specific Performance. Calibr acknowledges and agrees that Calibr's obligations set forth in Section 2.1.1, Section 2.1.2, Section 2.2.1, Section 2.6.1, Section 2.10, Section 5.3 and Section 10.3.5, are unique and that AbbVie would not have entered into this Agreement in the absence of such obligations, and that a... |
13.12 Waiver and Non-Exclusion of Remedies. Any term or condition of this Agreement may be waived at any time by the Party that is entitled to the benefit thereof, but no such waiver shall be effective unless set forth in a written instrument duly executed by or on behalf of the Party waiving such term or condition. Th... |
13.13 No Benefit to Third Parties. Except as provided in Article 11, the covenants and agreements set forth in this Agreement are for the sole benefit of the Parties and their successors and permitted assigns and they shall not be construed as conferring any rights on any other Persons. |
13.14 Further Assurance. Each Party shall duly execute and deliver or cause to be duly executed and delivered, such further instruments and do and cause to be done such further acts and things, including the filing of such assignments, agreements, documents and instruments, as may be necessary or as the other Party may... |
13.15 Relationship of the Parties. It is expressly agreed that Calibr, on the one hand, and AbbVie, on the other hand, shall be independent contractors and that the relationship between the two Parties shall not constitute a partnership, joint venture or agency, including for all tax purposes, and shall not take the po... |
13.16 HSR Act Compliance. If AbbVie determines that an HSR Filing is required with respect to AbbVie's exercise of the CD19 License Option or Platform Option, as applicable, the Parties shall cooperate to make an HSR Filing within fifteen (15) Business Days after (a) with respect to the CD19 License Option, the date up... |
13.17 References. Unless otherwise specified, (a) references in this Agreement to any Article, Section or Schedule shall mean references to such Article, Section or Schedule of this Agreement, (b) references in any Section to any clause are references to such clause of such Section and (c) references to any agreement, ... |
13.18 Construction. Except where the context otherwise requires, wherever used, the singular shall include the plural, the plural the singular, the use of any gender shall be applicable to all genders and the word "or" is used in the inclusive sense (and/or). Whenever this Agreement refers to a number of days, unless o... |
13.19 Amendment and Restatement. This Agreement constitutes an amendment and restatement of the Original License Agreement effective from and after the A&R Effective Date. All rights or obligations owing under the Original License Agreement, or based on facts or events occurring or existing prior to the A&R Effective D... |
13.20 Performance by Affiliates. AbbVie may use one (1) or more of its Affiliates to perform its obligations and duties hereunder and such AbbVie Affiliates are expressly granted certain rights herein; provided, that each such Affiliate will be bound by the corresponding obligations of AbbVie and, subject to an assignm... |
13.21 Counterparts. This Agreement may be executed in two (2) or more counterparts, each of which shall be deemed an original, but all of which together shall constitute one and the same instrument. This Agreement may be executed by facsimile, .pdf format via email or other electronically transmitted signatures and suc... |
[SIGNATURE PAGE FOLLOWS.] |
THIS AGREEMENT IS EXECUTED by the authorized representatives of the Parties as of the A&R Effective Date. The Scripps Research Institute AbbVie Global Enterprises Ltd. By: [signature] Name: Peter G. Schultz Title: President/CEO By: [signature] Name: Azita Saleki-Gerhardt, Ph.D. Title: President [Signature Page to Amend... |
CD19 AUTOIMMUNE PLAN 2023-2025 This Work Plan summarizes the activities and deliverables for autoimmune preclinical and clinical research which may be optionally triggered by AbbVie through the CD19 Autoimmune Option. The goal of this work plan is to demonstrate the potential of the switchable CAR-T cell platform to be... |
Work Plan Initial CD19 Autoimmune Plan Period Covered Preclinical: models expected to be carried out over 2-3 years Clinical: expected to require approximately 3 years. Final timeline and number of patients are subject to discussion with AbbVie. Start date tbd (AbbVie option) Deliverable Preclinical: in vivo efficacy (... |
Outline of Work Plan: Background Early clinical studies have demonstrated efficacy of CART19 in lupus via "immune reset" (N Engl J Med 2021; 385:567). CAR-T mediated elimination of B cells expected to be more efficacious than targeting with monoclonal antibody due to depth of B cell depletion (elimination of autoreacti... |
[THIS IS FIGURE/CHART: A diagram showing a flow of concept development from "Potential to Establish CD19 sCAR-T as 'One Time Autoimmune Treatment'" through various phases of development and clinical applications] |
Preclinical (a) Calibr will perform additional studies to evaluate therapeutic effect of sCAR-T + CD19 in animal models of autoimmunity beyond lupus, which may include: a. Type 1 diabetes mellitus b. Multiple sclerosis c. Inflammatory bowel disease d. Rheumatoid arthritis (b) For each model, Calibr will perform a dose ... |
Clinical (a) Calibr will be responsible for carrying out a Phase I clinical study in subjects with lupus, including but not limited to regulatory, cell manufacturing, and operational activities. (b) Calibr and AbbVie will discuss and align on a clinical development plan for lupus which will include patient population. ... |
Schedule 1.80: CD19 Plan Activities related to Switch for CD19 program Calibr will conduct CD19 program |
Component Activities Requirements Data Deliverables Responsible Switch Production for pre-IND and IND Chevron 1 Development of formulation and manufacturing process, analytical testing and stability assessment for Fab switch per Agency requests. Manufacturing, testing, release and stability. Quality Oversight Label, sh... |
Tissue cross reactivity with anti-CD19 switch on panel of human tissues Chevron 2 Assess potential cross-reactivity of anti CD19 switch with panel of human tissues using immunohistochemical techniques. GLP study to be carried out with material from switch engineering or GMP run. Preparation of anti CD19 switch test art... |
IND enabling GLP Toxicology Study: A GLP study (or studies) in non-tumor bearing animals as guided by input from the FDA to assess the safety of the anti-CD19 switch will be conducted in the appropriate/ designated preclinical species. Chevron 3 Exact study design TBD and will be based on prior preclinical data and wit... |
Activities related to sCAR-T cells for CD19 Program |
Component Activities Requirements Data Deliverables Responsible Lentivirus Vector Product Manufacture Chevron 4 Transfer of packaging and transgene plasmids to CMO. Completion of GMP vector product manufacture to support nonclinical testing, cell manufacturing engineering run(s), release, stability and clinical trial. ... |
sCAR-T cell Process Development. Cell Production at CMO for IND Chevron 5 Process development and analytical development that demonstrates, robustness, reproducibility. Manufacturing, Release, Label, ship, etc. Development of processes for cell processing, cell culture, cell harvest, cryopreservation, stability, thaw a... |
Tissue cross reactivity with sCAR on panel of human tissues Chevron 6 Assess potential cross-reactivity of sCAR scFv with panel of human tissues using immunohistochemical techniques. GLP study. Preparation of the scFv of the sCAR as test article by expression of scFv-Fc fusion protein (or alternatively scFv-His tagged ... |
In vivo efficacy in Xeno model in NSG mice to support IND (Definitive mouse model aka GLP/ GLP-like model) Chevron 7 Assess in vivo activity of sCAR-T with anti-CD19 switch in appropriate preclinical efficacy model to support IND package. Efficacy analysis of sCAR-T to support IND package. Xenograft model will be NALM-... |
Clinical Regulatory for CD19 program |
Component Activities Requirements Data Deliverables Responsible pre- IND meeting with Agency Star 8 Establish communication with CBER on the CD19 preclinical, manufacturing, tox, and clinical plans through pre-pre IND interaction. Deliver to Agency: (i) Summary description of the intended clinical product (ii) Summary ... |
Clinical CRO contracting Chevron 9 Evaluate and select a clinical CRO to support the trial. Contracting the CRO and relevant third party vendors. Develop budget and timeline with the CRO and vendors. Scope to include management activities an integrated solutions services including but not limited to clinical operation ... |
pre- IND meeting with Agency Chevron 10 Receive formal feedback from CBER on CD19 program through pre-IND meeting. Deliver to Agency: (i) product name, IND number (ii) structure (iii) indication (iv) dosage form, ROA, regimen (v) list of attendees (vi) program background, preclinical, development, clinical strategy (vi... |
Clinical trial start-up, site initiation, and IRB review Chevron 11 Qualified clinical CRO to manage clinical start-up activities. Selection of qualified clinical sites and investigators to conduct the study. Conduct site initiation visits and CRA trainings. Obtain local or central regulatory approvals. Establish ICF, ... |
IND Chevron 12 Preparation of the IND package. Publish and eCTD submission to the FDA Deliver to Agency: Signed Form FDA 1571, Form FDA 1572 Statement of Investigator, Form FDA 3674 Certification of Compliance; (i) TOC (ii) Introductory statement and general investigational plan (iii) Investigator's brochure (iv) Clini... |
CMC documentation Chevron 12 CMC reports, data and records that describe process / method development. Records pertaining to GMP manufacture, testing, and lot release CTD sections and CMC reports, including letters of cross reference to BMFs Calibr to prepare IND documentation. |
Phase I clinical trial execution Chevron 13 Calibr to conduct phase I clinical study for CD19 program through the clinical CRO. Manufacture and supply CAR-T cell products to patients. Enroll and treat patients under GCP guidelines. Monitor and report SAE to regulatory authorities. Conduct interim onsite monitoring visi... |
Clinical study report publishing and submission Chevron 14 Compilation of a core clinical study report Data package that include tables, listings figures, and datasets, interim and draft Clinical Study Report. Calibr to review and approve TLF and report. Calibr responsible for oversight over clinical CRO and delivery o... |
Key CMC goals: CAR Lentivirus intermediate: • Timing for GMP manufacturing - Aug/Sept 2018 • Timing for Release - Jan/Feb 2019 • Expected yield - ≥ 50 mL of 107-108 TU/mL CD19 switch DS: • Timing for GMP manufacturing - Nov 2018 • Timing for Release - Jan 2019 CD19 switch DP: • Timing for GMP manufacturing - Jan 2019 •... |
1.80 – CD19 Clinical synopsis: Protocol Number CBR-CLBR001/SWI019-3001 |
Title A PHASE 1, OPEN-LABEL STUDY OF THE COMBINATION OF CLBR001, AN ENGINEERED AUTOLOGOUS T-CELL PRODUCT, AND SWI019, AN ANTIBODY-BASED BIOLOGIC, IN PATIENTS WITH CD19+ FOLLICULAR LYMPHOMA |
Sponsor CALIBR |
Name of Investigational Product CLBR001 (Cellular Product) Chimeric antigen receptor T (CAR-T) cell product that comprises the patient's T cells and a novel "switchable" chimeric antigen receptor (sCAR-T), code name ENH655. From extracellular to intracellular, the ENH655 structure consists of an scFv followed by an IgG... |
Phase 1 |
Investigator/Study Center TBD |
Objectives: Primary Objective • To determine the safety and tolerability of CLBR001 • To determine the maximum tolerated dose (MTD) of SWI019 when administered intravenously after administration of CLBR001 |
Secondary Objectives • To measure the depletion of B cells in response to dose escalation of SWI019 switch after administration of CLBR001 • To measure serum cytokines in response to dose escalation of SWI019 switch after administration of CLBR001 • To determine the in vivo survival and expansion or elimination of CLBR... |
Exploratory Objective • To assess exploratory biomarkers, including markers of immune function and inflammatory pathways |
Number of Subjects Total enrollment is approximately 36 patients |
Study Design and Methodology Single-arm, open-label, dose-escalation, Phase 1 study in patients with CD19+ Follicular Lymphoma. Sentinel dosing will be applied in all dose cohorts. |
At entry subjects will be staged and the suitability of their T cells for CAR-T manufacturing will be determined. Subjects who have adequate T cells will undergo leukapheresis to obtain peripheral blood mononuclear cells (PBMC) for CART manufacturing. From a single leukapheresis, the intention is to harvest at least [x... |
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