DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Applicants Amendments/Arguments
The specification was amended to include a description of Figure 3D in the brief drawing description. The amendment made to claim 34 has also corrected the claim objection so that has been withdrawn. The claims have been amended/corrected in a manner that allows for the 112(b) rejection for indefiniteness to be withdrawn.
Because of the recent amendments, the former rejections have been withdrawn and new rejections put forward. All the references cited in the rejections are already of record.
Claims 14,17-20,26,31,33-34,86-88 are under examination.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 14,17,19-20, and 86-87 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bromberg (WO 2018191348)
Bromberg discloses a process for manufacturing a T-cell population comprising T-cells with enhanced immune properties, the process comprising isolating or selecting from a sample a T-cell population comprising CD49f+ T cells and/or enriching a sample containing T cells for CD49f+ T-cells, wherein the CD49f T-cells constitute at least 80% of the T cells in the population, or enriching a sample containing T-cells for CD49f+ T cells, thereby manufacturing a T-cell population comprising T-cells with enhanced immune properties (Page 12, lines 13-25; Figure 23C—T cells exposed to a LTβR-NFкB signaling pathway inhibitor express very high amounts of CD49f+) as in instant Claim 14. Bromberg discloses wherein T-cell containing sample is enriched for T-cells of interest (Page 12, lines 13-25; Figure 23C) as in instant Claim 17. Bromberg discloses wherein the CD49f+ have a stem-like phenotype (Page 12, lines 13-25; Figure 23C) as in instant Claim 19. Bromberg discloses wherein the enhanced immune properties are relative to a control (Abstract; Page 12, lines 13-25; Figure 23C) as in instant Claim 20. Bromberg discloses wherein the enhanced immune properties are selected from increased responsiveness in immunotherapy (Abstract) as in instant Claim 86. Bromberg discloses wherein the T cells are naïve CD4 T cells (Page 12, lines 13-25; Figure 23C) as in instant Claim 87.
The reference anticipates the claim limitations.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 14,17-20,26,86-88 are rejected under 35 U.S.C. 103 as being unpatentable over Bromberg (WO 2018191348) in view of Gattinoni et al. “A human memory T-cell subset with stem cell-like properties” Nat. Med: 17(10): 1290-1297”.
Bromberg applies as above to teach claims 14,17,19-20, and 86-87. Bromberg teaches a composition for inhibiting cell motility which is used to treat unwanted conditions such as tissue graft rejection, inflammation, contact hypersensitivity, or cancer (Abstract and Page 4 of Bromberg). Bromberg accomplishes this goal by blocking classical or the non-classical LTβR-NFкB signaling pathway using inhibitors. The target cells are T cells and dendritic cells (Page 95, lines 14-17 of Blomberg). Inhibitors of LTβR-NFкB signaling pathway can be used to treat diseases characterized by altered cell migration that include but are not limited to inflammation, graft rejections, contact hypersensitivity, and cancer (Page 4, lines 3-6 of Bromberg).
Bromberg does not state that the T cells treated are memory T cells. Gattinoni teaches enriching a sample containing stem memory T cells (Tscm) (Abstract, Pages 2-4 of Gattinoni). In the abstract, Gattinoni states, “compared to known memory populations, these lymphocytes displayed increased proliferative capacity, more efficiently reconstituted immunodeficient hosts and mediated superior anti-tumor response in a humanized mouse model (abstract).” This article is stating that these particular cells have improved anti-cancer benefits. It would have been obvious to an artisan of ordinary skill at the time of effective filing to have exposed these cells to an inhibitor of the LTβR-NFкB signaling pathway as taught in Bromberg to improve cancer treatment. An artisan would have been motivated to have treated Gattinoni’s T cells with an inhibitor of LTβR-NFкB signaling pathway because Bromberg teaches that cancer can be treated by administering LTβR-NFкB signaling pathway inhibitors to T cells which also simultaneously enriches/selects for a population of CD49+ cells (Page 95, lines 14-22 of Blomberg). Administering the LTβR-NFкB signaling pathway inhibitors, would further improve the memory cells’ ability to treat cancer (Abstract and Page 95, lines 14-22 of Blomberg) as in instant Claims 18- 19 and 87
Dependent claims taught by Gattinoni
Gattinoni teaches T cell memory population has enhanced proliferative and survival capabilities when compared to other types of T cells (Page 6, Increased Proliferation Capacity, Survival and Anti-Tumor Activity of Tscm cells) as in instant Claims 20 and 86, Gattinoni teaches exposing the Tscm cells to stimulation/activation with a α-CD3, CD2, CD28 beads to produce antigen specific T cells (Page 3, TSCM possesses attributes of convention memory section) as in instant Claim 26. Gattinoni’s cells are enriched for memory T phenotype (Pages 3-5 of Gattinoni). The cells of Gattinoni are positive for BCL-2, LFA-1,CXCR3,CXCR4, CD38, CD31, CD45RA, CCR7, CD27, IL2Rα, ILRβ, IL7Rα,CD69,41BB, CCR5,CD28,CD57, and CD95 (Central memory cell markers) (Page 3 and Figure 1 of Gattinoni) as in instant Claim 88.
Bromberg teaches that treating CD4+ naïve cells with LTβR-NFкB inhibitors selects for cells that are positive for CD49f+ and improves the ability of the host to fight cancer. Bromberg does not teach treating memory T cells with such inhibitors. It would have been obvious to have treated Gattinoni’s memory cells with LTβR-NFкB inhibitors because those inhibitors prevent aberrant cell migration associated with unwanted cancer. An artisan would have been strongly motivated to have treated such memory cells taught in Gattinoni because they are already known to have anti-tumor properties/anti-cancer properties and Bromberg’s treatment with LTβR-NFкB inhibitors would further prevent aberrant cell migration related to cancer (thus providing an additional defense against cancer). Given the teachings of the cited references and the level of skill of an ordinary skilled artisan at the time of applicants’ invention, it must be considered, absent evidence to the contrary, that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
All of the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predicable results to one of ordinary skill in the art at the time of the invention (See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.s and Ph.D.s. They will be medical doctors, scientists, or engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in molecular biology, cell culture, and immunotherapy. Therefore, the level of ordinary skill in this art is high.
Claims 14,17-20,26,31,33-34, 86-88 are rejected under 35 U.S.C. 103 as being unpatentable over Bromberg (WO 2018191348) in view of Gattinoni et al. “A human memory T-cell subset with stem cell-like properties” Nat. Med: 17(10): 1290-1297” and Dotti (US 20190048085).
Bromberg and Gattinoni apply as above to teach claims 14,17-20,26,86-88. Bromberg does not teach that its T cells can be genetically modified to have TCR (T cell receptors) or a CAR (chimeric antigen receptor). However, Gattinoni states that its T cells can be genetically engineered to include a TCR (T cell receptor) or a CAR (chimeric antigen receptor) to treat and target cancer and infectious disease. Gattinoni does not teach more specific processes of developing CAR/TCR structures as claimed. Dotti teaches that a therapeutic strategy of engineering immune cells to express chimeric antigen receptors that are capable of targeting tumor cells involves developing a CAR T cell with an extracellular antigen recognition domain/ectodomain, a transmembrane domain, and an intracellular signaling domain (Paragraphs 4 and 54 of Dotti). The extracellular domain provides antigen recognition and is most commonly an antigen binding molecule (e.g. scFv) (Paragraph 54 of Dotti). In order to create such a CAR T-cell, a nucleic acid is delivered into the target T cell with an expression vector (a transduction process) (Paragraphs 173-175 of Dotti).
It would have been obvious to an artisan of ordinary skill at the time of effective filing to have used the CAR construct method taught by Dotti to create the CAR T cell taught in Gattinoni. An artisan would have been motivated to have used Dotti’s CAR construct in order to effectively target cancer cells (Abstract of Dotti). There would have been a high expectation for success using the CAR structures taught in Dotti with the system taught in Gattinoni because the CAR structures taught in Dotti can effectively target cancer cells (Abstract of Dotti) as in instant Claims 14,31,33-34
Bromberg teaches that treating CD4+ naïve cells with LTβR-NFкB inhibitors which selects for cells that are positive for CD49f+ and improves the ability of the host to fight cancer. Bromberg does not teach treating memory T cells with such inhibitors. It would have been obvious to have treated Gattinoni’s memory cells with LTβR-NFкB inhibitors because those inhibitors prevent aberrant cell migration associated with unwanted cancer. An artisan would have been strongly motivated to have treated such memory cells as those taught in Gattinoni because they are already known to have anti-tumor properties/anti-cancer properties suggesting clinical use/benefits and Bromberg’s treatment with LTβR-NFкB inhibitors would further prevent aberrant cell migration related to cancer (thus providing an additional defense against cancer).
Gattinoni teaches that its memory T cells can be combined with CAR gene engineering in order to produce a T cell that can successfully target cancers and/or infectious diseases. Gattinoni does not clearly describe a transduction process in which nucleic acid is successfully introduced into T cells to create a CAR T cell. However, an artisan would have been motivated to have used the transduction process taught by Dotti since Dotti uses a vector that is able to introduce nucleic acid into T cells to successfully form CAR T cells. Given the teachings of the cited references and the level of skill of an ordinary skilled artisan at the time of applicants’ invention, it must be considered, absent evidence to the contrary, that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
All of the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predicable results to one of ordinary skill in the art at the time of the invention (See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.s and Ph.D.s. They will be medical doctors, scientists, or engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in molecular biology, cell culture, and immunotherapy. Therefore, the level of ordinary skill in this art is high.
Conclusion
All claims stand rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN K VAN BUREN whose telephone number is (571)270-1025. The examiner can normally be reached M-F:9:30am-5:40pm; 9:00-10:00pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached at 571-272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
LAUREN K. VAN BUREN
Examiner
Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
Prosecution Insights