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 .
Status of the Claims
Claims 1-4,8-9,12,14,21,25-26,28,30-32,34,36 and 38-39 are currently pending in the Application and are examined on the merits below.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
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 1-4, 6, 8, 9, 12, 14, 21 are rejected under 35 U.S.C. 103 as being unpatentable over Qin (CN111320677A), and further in view of Tanaka et al (Clin Cancer Res; 23(14) July 15, 2017).
Claim 1 describes a method of generating memory T cells within a mammal through (a), administration of a population of T cells with “different endogenous T cell receptors” to a mammal and thereafter (b) administering a “first antigenic composition to said mammal”. As a result the CAR-T cells form memory T cells. Thereafter (c), a “second antigenic composition comprising said antigen” is administered to said mammal. The applicant thus describes a variation of a prime and boost vaccination method.
Regarding the claim 1 the disclosure of Qin describes adoptive immune cell therapy in combination with oncolytic virus treatment/ vaccine modalities (abstract). Specifically for example the disclosure provides for combination therapy of treating cancer through administration of adoptive immune cells to a subject having cancer (claim 43), wherein the adoptive immune cells may be derived from PBMC from a subject having cancer and thereby modified with a chimeric antigen receptor (CAR) (claim 48). The chimeric antigen receptor may be directed to a tumor antigen which the subject suffers from such as cell surface proteins carcinoembryonic antigen (CEA) CA125 or Her2 for example (claim 52). The disclosure further indicates that the host may be treated by the same virus system for a plurality of times within a certain time period, therefore satisfying the requirements of the claim 1(c) (p10 paragraph 11).
Regarding the feature incorporated into the claim which describes that the CAR-T cells form memory T cells in the mammal which may thereafter be stimulated through their endogenous TCR to form effector T cells this is an inherent feature of the claimed method described by the disclosure of Qin for instance. Supporting this for example the further disclosure of Tanaka et al (Clin Cancer Res; 23(14) July 15, 2017)(of record) describes an in-vitro system in which GD2 tumor antigen directed CAR-T cells are additionally stimulated with VZV (varicella zoster, “chicken pox”) viral antigens thus stimulating cells through endogenous pre-existing viral peptide directed TCR. The “dual” TCR T cells thus produced are capable of recognizing both GD2 antigen through the CAR molecule as well as the endogenous TCR directed to VZV antigens. The stimulation of cells with VZV peptides for example provides cells which comprise at least some CD3+CD45RO+ (memory phenotype) T cells after culture (figure 1D). Thus an in-vivo procedure in which a peptide and/or viral vaccine is provided in conjunction with a CAR-T modified T cells would likewise be expected to produce memory T cells directed to viral antigens/ immunized peptide antigen which have a “memory” phenotype. Furthermore said CAR-T / endogenous TCR memory T cells may be further stimulated through a second vaccination procedure utilizing the same viral peptide antigens/ antigenic peptide for the purposes of increasing the number of the viral specific cells and in the case of dual specific cells, tumor directed CAR-T cells as well (figure 2, A-C). The disclosure of Tanaka emphasizes that such a protocol may therefore inherently provide the above effects beneficially as a means to “break homeostatic control of memory T cells and produce antigen specific T cell expansion in-vivo”. Expansion of GD2 tumor specific CAR-T cells can thus be beneficially piggybacked onto viral antigen specific memory T cell expansion thereby targeting tumor expressing the CAR-T antigen and reducing tumor burden in-vivo.
Regarding the instant claim 2 wherein the mammal is human the disclosure of Qin specifically treats cancer in a human mammal (p2, paragraph 6).
Regarding instant claim 3 the cancer that may be treated may be breast cancer for example (p. 14, paragraph 8).
Regarding the instant claim 4 the disclosure of Qin is primarily concerned with the coadministration of “Tcm” CAR-T cells as opposed to T cell naïve CAR-T cells. However the disclosure of Qin additionally indicates that modified immune cells of the invention may comprise peripheral blood mononuclear cells which naturally comprise a naïve T Cell population (claim 43-47, p4). It would be obvious to therefore utilize a population of T cells derived from peripheral blood mononuclear cells which, as naïve T cells, naturally comprise heterogenous endogenous T cell receptors as an appropriate CAR-T cell population previously disclosed by Qin.
Regarding the instant claim 6 for example as indicated above the CAR may target CA125 or Her2, a target known to be found on breast cancer.
Regarding the instant claims 8 and 9 the virus of Qin is an oncolytic virus (p13, paragraphs 10-15) .
Regarding the instant claim 12 the disclosure of Qin (p13, paragraphs 10-15) describes that oncolytic virus “vaccines” may be utilized which express target tumor antigens may utilized to thereby increase the selectivity of the virus for cancer cells.
Regarding the instant claim 14 and the description that the first antigenic composition “comprises” an antigenic peptide for example , as indicated for the instant claim 12, the disclosure of Qin describes that virus may include exogenous peptide derived from target tumor antigens. The virus as the antigenic composition thereby “comprises” an antigenic peptide as interpreted by the examiner. Furthermore the oncolytic viral composition of Qin further may comprise an additional anti-tumor agent, the agent may be a polypeptide for instance as in claim 7 of Qin for instance. It would be obvious to therefore considering the disclosure of Qin to provide an antigenic composition in which the composition “comprises” an antigenic peptide derived from the targeted tumor for example as disclosed by Qin. One would do so for the purposes of providing tumor specific peptide vaccination in addition to for example chimeric antigen receptor targeted T cells to the subject thereby providing beneficial synergistic effects as indicated by the disclosure of Qin.
Regarding the instant claim 21 for example the disclosure of Qin indicates that viral preparations may be administered a plurality of times as indicated for the claim 1 above. The disclosure of Qin further indicates that following a first vaccination with a select tumor antigen for example an oncolytic virus vaccine, the subject develops an immune response within about 4 days extending to for months , years or life of the subject (p10, paragraphs 1-8). Furthermore the disclosure provides that secondary administration of an oncolytic virus may occur for example about after about 2-4 days or more (5 days or greater). The disclosure additionally indicates that oncolytic virus vaccine stimulation of endogenous specific T cell activity peaks at 5 days after administration of the vaccine (example 11, p21, p24 paragraph 3). It would thus be obvious to readminister the antigenic composition of Qin (oncolytic virus) at an interval of 5 days or greater as a matter of routine optimization of the production of a secondary immune response in a subject as an appropriate time interval disclosed by Qin.
Claims 25, 26, 28, 30, 31, 32, 34, 36, 38, 39 are rejected under 35 U.S.C. 103 as being unpatentable over Qin (CN111320677A), and further in view of Tanaka et al (Clin Cancer Res; 23(14) July 15, 2017).
Claim 25 describes a method of generating memory T cells within a mammal through administration of a population of T cells with “different endogenous T cell receptors” to a mammal and thereafter administering an “antigenic composition to said mammal”. As a result the CAR-T cells form memory T cells. The further limitations describing that at least some of the cells of the population of CAR-T cells form memory T cells within said mammal , wherein the endogenous TCR is specific for “an antigen of said antigenic composition”, are an inherent result of performing the active steps of the claimed method. Thus conceptually, the applicant describes the process through which memory T cells naturally form through activation of a TCR either CAR derived or the naturally occurring endogenous TCR.
The claim 25 therefore significantly reiterates the limitations of claim 1 above without including the step (c) wherein there is a second administration of an antigenic composition. Regarding the claim 25 therefore as indicated above the disclosure of Qin specifically provides for combination therapy of treating cancer through administration of adoptive immune cells to a subject having cancer (claim 43) , wherein the adoptive immune cells may be derived from PBMC from a subject having cancer and thereby modified with a chimeric antigen receptor (CAR) (claim 48). The chimeric antigen receptor may be directed to a tumor antigen which the subject suffers from such as cell surface proteins carcinoembryonic antigen (CEA) CA125 or Her2 for example (claim 52). Regarding the feature incorporated into the claim which describes that the CAR-T cells form memory T cells in the mammal which may thereafter be stimulated through their endogenous TCR to form effector T cells this is a latent/inherent feature of the claimed method described by the disclosure of Qin for instance as significantly explained and supported in the rejection of claim 1 above. It would thus be obvious to arrive at the method of claim 25 considering the disclosure of Qin for the purposes of providing a beneficial combination therapy in which for example CAR-T cells may be beneficially reactivated/expanded in-vivo through manipulation of endogenous TCR stimulation.
Regarding the instant claim 26 , wherein the mammal is human, the disclosure of Qin specifically treats cancer in a human mammal (p2, paragraph 6).
Regarding the instant claim 28 for example the CAR of the invention of Qin may target a “tumor specific antigen” as CA125 or Her2, a target known to be found on breast cancer as indicated for claim 25.
Regarding the instant claims 30 and 31 for example the disclosure of Qin for instance provides a therapeutic oncolytic virus (p13, paragraphs 10-15) .
Regarding the instant claim 32 for example the oncolytic virus of the invention may be preferably for example VSV (a vesicular stomatitis virus) as well as reovirus, Newcastle disease viruses and measles virus among others (p5, para 5-6). It would be obvious to therefore utilize said viruses as a previously disclosed effective oncolytic virus in the method disclosed by Qin.
Regarding the instant claim 34 the disclosure of Qin (p13, paragraphs 10-15) describes that oncolytic virus “vaccines” may be utilized which express target tumor antigens may utilized to thereby increase the selectivity of the virus for cancer cells. It would be obvious to therefore utilize virus which additionally express a target tumor antigen for the purposes of providing antigen which may be recognized by endogenous TCR thereby providing additional tumor specific recognition to CAR-T cells, as a means of avoiding tumor escape mechanisms.
Regarding the instant claim 36 and the description that the antigenic composition “comprises” an antigenic peptide for example , as indicated for the instant claim 12, the disclosure of Qin describes that virus may include exogenous peptide derived from target tumor antigens. The virus as the antigenic composition thereby “comprises” an antigenic peptide as interpreted by the examiner. Furthermore the oncolytic viral composition of Qin further may comprise an additional anti-tumor agent, the agent may be a polypeptide for instance as in claim 7 of Qin for instance. It would be obvious to therefore considering the disclosure of Qin to provide an antigenic composition in which the composition “comprises” an antigenic peptide derived from the targeted tumor for example as disclosed by Qin. One would do so for the purposes of providing tumor specific peptide vaccination in addition to for example chimeric antigen receptor targeted T cells to the subject thereby providing beneficial synergistic effects as indicated by the disclosure of Qin.
Regarding the claim 38, 39, the disclosure of Qin describes that human subjects may for example have cancer which may be for example colon cancer (claim 31, p3 of Qin translated). It would thereby be obvious to utilize the method of Qin in a method as indicated for the purposes of effectively treating a mammal which suffers from the disclosed diseases.
Conclusion
Summary: No claims are allowed.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Janet L Epps-Smith can be reached at 571-272-0757. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRIAN HARTNETT/Examiner, Art Unit 1644
/DANIEL E KOLKER/Supervisory Patent Examiner, Art Unit 1645