DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant's amendment and remarks, filed 3/23/26, are acknowledged.
Claims 1, 5, 25-26 have been amended.
Claims 1, 3-5, 9, 13, 25-26, 30-37, 39, 41, 43, 46-47, 50 are pending.
Claims 32-34, 36-37, 39, 41, 43, 46-47, and 50 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Claims 1, 3-5, 9, 13, 25-26, and 30-31 are being acted upon.
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.
Claims 1, 3-5, 9, 13, 25-26, and 30-31 are rejected under 35 U.S.C. 103(a) as being unpatentable over WO 2018/002924, in view of US 2018/0207272 and US 2016/0340649.
WO 2018/002924 teaches a method of generating a population of tolerance inducing cells (i.e. veto cells, see page 17) comprising providing a population of T cells comprising at least 70% memory CD8+ T cells, culturing said population of cells with an antigen under conditions to allow enrichment of antigen reactive cells that are tolerance inducing T cells endowed with anti-disease activity, and non-GVH inducing and having a Tcm phenotype (see page 3 and 17, in particular). WO 2018/002924 further teaches genetically modifying said Tcm cells to express specific genes (see page 18, in particular).WO 2018/002924 teaches providing said population of memory CD8+ T cells by treating PBMC with an agent that depletes CD4+, CD56+, and CD45RA+ cells to obtain CD8+CD45RO+CD45RA- T cells (i.e. to create a population devoid of CD45RA+ cells, see pages 4 and 19, in particular). WO 2018/002924 teaches that the T cell population is cultured with said antigen in the presence of IL-21 to allow enrichment of antigen reactive cells and also culturing said antigen reactive cells in the presence of IL-21, IL-15, and/or IL-7 to allow proliferation of Tcm T cells (see page 4, 14 in particular). WO 2018/002924 teaches that said antigen comprises third party antigens, and that the method is conducted ex-vivo (see pages 8 and 27). WO 2018/002924 teaches Tcm phenotype of CD3+CD8+CD62L+CD45A-CD45RO+ (see page 17, in particular). WO 2018/002924 teaches that the cells have anti-disease activity, wherein the disease is a malignant disease, tumor, cancers, or an infectious disease (see page 8-10, in particular).
The reference differs from the claimed invention in that it does not explicitly teach transducing with a polynucleotide encoding a CAR on days 4-6.
The ‘272 publication teaches Tcm cells being tolerance inducing/veto cells generated by culture with antigens and cytokines, wherein the Tcm cells are transduced with a polynucleotide encoding a CAR (See page 2, 5, 16, in particular). The ‘272 publication teaches that the CAR comprises a co-stimulatory domain and T cell receptor signaling domain (see page 2 and 8-9, in particular). The ‘272 publication teaches that the CAR comprises and extracellular antigen binding domain that binds a viral antigen or a tumor antigen (see page 2, in particular). The ‘272 publication teaches genetic modification with a CAR redirects the T cells toward the target antigen, and that said Tcm cells genetically modified to express a CAR can be used to combat disease while inducing veto activity and provide a universal product for immunotherapy that targets a disease antigen while avoiding graft versus host disease (see pages 4-5, in particular). The ‘272 publication teaches that the CAR can be introduced with a selectable marker to facilitate identification and selection of the CAR expressing cells (see page 17, in particular).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to genetically modify by transducing with a polynucleotide encoding a CAR, as taught by the ‘272 publication, as the type of genetic modification in the method of producing T cells as taught by WO 2018/002924. The ordinary artisan at the time the invention was made would have been motivated to do so with a reasonable expectation of success, because the ‘272 publication teaches that genetic modification of Tcm to express a CAR redirects the T cells toward a target antigen, and that said CAR modified Tcm cells can be used to combat disease while inducing veto activity and provide a universal product for immunotherapy that targets a disease antigen while avoiding graft versus host disease.
Regarding the limitation that the transduction is on days 4-6, WO 2018/002924 also teaches that the first culture wherein the T cells are activated in response to antigens and IL-21 is effected for 12 hours to 5 days and the second culture in IL-12, IL-15 and/or IL-17 is effected for 12 hours to 10 days (See page 7, in particular). The ‘272 publication teaches the same culture timeframe (see page 16, in particular).
The ‘649 publication teaches transducing Tcm cells with a CAR, wherein the T cells are transduced within 5 days of activation, and wherein the T cells are cultured in cytokines such as IL-15 (see paragraphs 57-58 and 77, in particular).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the invention was made to optimize the timeframe of transduction based on the ‘649 publication, in the method made obvious by WO 2018/002924 and the ‘272 publication. For example, the ‘649 publication teaches activating Tcm cells in a culture comprising cytokines such as IL-15 and that the Tcm can be transduced within 5 days of the start of the culture. The method made obvious by WO 2018/002924 and the ‘272 publication involves a first step of culturing with antigens to select antigen reactive (i.e. activated cells) that can be effected for 12 hours to 5 days, and a second step of further culturing in cytokines such as IL-15. Therefore, the ordinary artisan could readily envision transducing the cells on day 4-5, during the first or second culture of the instant claims based on the teachings of the cited references. For example, one could envision transducing the resulting Tcm on day 4-5 after the antigen activation step of the culture method made obvious by WO 2018/00294 and the ‘272 publication, given that the ‘649 publication teaches CAR transduction should occur within 5 days of activation. Thus optimizing a timeframe of, for example, day 5 of culture would be well within the purview of the ordinary artisan based on the teachings of the cited references.
Regarding claim 31, given that the ‘272 publication teaches that the CAR can be introduced with a selectable marker to facilitate identification and selection of the CAR expressing cells, it would be obvious that when selecting the CAR expressing cells, one would arrive at a cell population in which at least 10% of the cells express the CAR.
Applicant’s arguments filed 3/23/26 have been fully considered, but they are not persuasive.
Applicant argues that the ‘649 publication merely describes an exemplary embodiment, wherein CAR transduction may occur within five days of CD3/CD28 activation, but does not identify any particular time point at all as critical or advantageous. Applicant further argues that the culture system in the ‘649 publication is different and relies on polyclonal stimulation which is a strong stimulation, whereas the claimed culture systems involves antigen driven activation. Applicant concludes that therefore the timeframe in the ’649 publication would not be predictive of the basis for performing transduction in an antigen driven culture system.
References may be relied upon for all that they suggest to the ordinary artisan. The ’649 publication teaches transduction within 5 days of activation, would render obvious 4-5 days after activation, for example. In the claimed method, and in the method of WO 2018/00294 and the ‘272 publication, the activation occurs in step b) in response to the third party antigens. Polyclonal CD3/CD28 activation is an alternative way to activate T cells which mimics the natural way T cells are activated via antigen. It would be obvious to apply the timeframe of transduction after T cell activation taught in the ‘649 publication, to the method of WO 2018/00294 and the ‘272 publication, wherein the T cells are activated by antigen stimulation, with a reasonable expectation of success.
Applicant further argues that none of the cited references recognize the time of transduction as a result-effective variable.
The ‘649 publication does recognize time of transduction as a result effective variable in that it specifically points out that it should occur within a particular 5 day timeframe.
Applicant further argues that the specification in Figure 5 demonstrates that the claimed timeframe is superior.
In figure 5, T cells were cultured for 3 days according to step b), and thereafter IL-15 and Il-7 was added, and the T cells were transduced with a particular pBullet retroviral vector on day 3, 5 or 7 after the initiation of antigen culture. Transduction was effective on all days, however, day 5 had increased percent transduction as compared to day 3 and 7. Any unexpected result must be commensurate in scope with the instant claims. For example, Applicant’s asserted superior result is on day 5, but the instant claims encompass day 4 or 6. Furthermore, the transduction was performed with a 3 day culture in step b), whereas the present claims encompass 1-5 days in step b). The superior results were with a specific type of retroviral vector, but the present claims broadly encompass any type of polynucleotide and any transduction procedure. The asserted superior results are not commensurate in scope with the instant claims.
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 3-5, 9, 13, 25-26, and 30-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-37 of U.S. Patent No. 10,961,504, in view of US 2018/0207272, and US 2016/0340649.
The ‘504 patent claims a method of generating a population non graft versus host disease (GvHD) inducing anti-viral, anti-bacterial and/or anti-tumor cells comprising a central memory T-lymphocyte (Tcm) phenotype, said cells being tolerance inducing cells and/or endowed with anti-viral, anti-bacterial and/or anti-tumor activity (i.e. anti-disease activity), and comprising: (a) providing a population of T cells comprising at least 50% memory T cells; (b) contacting said population of T cells with a viral or bacterial antigen or antigens (i.e. third party antigens) in the presence of IL-21 so as to allow enrichment of antigen reactive cells; and (c) culturing said cells resulting from step (b) in the presence of any of IL-21, IL-15 and/or IL 7 so as to allow proliferation of cells comprising said Tcm phenotype. The ‘504 patent claims that said memory T cells are depleted of CD4+, CD56+, and CD45RA+ T cells using an agent capable of said depletion (i.e. they are CD45RA- or devoid of CD45RA+ cells) and that memory cells are CD8+CD45RO+.
Although the ‘504 patent does not specifically claim transducing with a polynucleotide encoding a CAR, it would be obvious to do so based on the teachings of the ‘272 publication for the same reasons set forth above. Furthermore, optimizing the timeframe of transduction would be obvious over the teachings of the ‘272 publication and the ‘649 publication for the same reasons set forth above. Furthermore, it would be obvious to use a Tcm with a CD3+CD8+CD62L+CD45A-CD45RO+ phenotype, since both the ‘272 publication teaches a similar culture process for obtaining Tcm with said phenotype wherein they are useful for treating disease, such as a tumor or infection (see page 16, in particular).
Claims 1, 3-5, 9, 13, 25-26, and 30-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11,773,372 in view of in view of US 2018/0207272, and US 2016/0340649.
The ‘372 patent claims a method of generating a population non graft versus host disease (GvHD) inducing cells comprising a central memory T-lymphocyte (Tcm) phenotype, said cells being tolerance inducing cells and/or endowed with anti-disease activity, and comprising: (a) providing a population of T cells comprising at least 70% memory T cells; (b) contacting said population of T cells with an antigen or antigens in the presence of IL-21 so as to allow enrichment of antigen reactive cells; and (c) culturing said cells resulting from step (b) in the presence of any of IL-21, IL-15 and/or IL 7 so as to allow proliferation of cells comprising said Tcm phenotype. The ‘372 patent claims that said memory T cells are depleted of CD4+, CD56+, and CD45RA+ T cells using an agent capable of said depletion (i.e. they are CD45RA- or devoid of CD45RA+ cells) and that memory cells are CD8+CD45RO+. The ‘372 patent claims that the antigens can be viral antigens (i.e. third party antigens).
Although the ‘372 patent does not specifically claim transducing with a polynucleotide encoding a CAR, it would be obvious to do so based on the teachings of the ‘272 publication for the same reasons set forth above. Furthermore, optimizing the timeframe of transduction would be obvious over the teachings of the ‘272 publication and the ‘649 publication for the same reasons set forth above. Furthermore, it would be obvious to use a Tcm with a CD3+CD8+CD62L+CD45A-CD45RO+ phenotype, since both the ‘272 publication teaches a similar culture process for obtaining Tcm with said phenotype wherein they are useful for treating disease, such as a tumor or infection (see page 16, in particular).
Claims 1, 3-5, 9, 13, 25-26, and 30-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 12,391,916, in view of in view of US 2018/0207272, and US 2016/0340649.
The ‘916 patent claims a method that comprises generating a population non graft versus host disease (GvHD) inducing central memory T-lymphocyte (Tcm) phenotype, said cells being tolerance inducing cells and/or endowed with anti-disease activity for treating a malignant disease and comprising: (a) providing a population of T cells comprising at least 50% memory T cells; (b) contacting said population of T cells with an antigen or antigens so as to allow enrichment of antigen reactive cells; and (c) culturing said cells resulting from step (b) in the presence of cytokines so as to allow proliferation of cells comprising said Tcm phenotype. The ‘916 patent claims that said memory T cells are depleted of CD4+, CD56+, and CD45RA+ T cells using an agent capable of said depletion (i.e. they are CD45RA- or devoid of CD45RA+ cells) and that memory cells are CD8+CD45RO+.
Although the ‘916 patent does not specifically claim transducing with a polynucleotide encoding a CAR, it would be obvious to do so based on the teachings of the ‘272 publication for the same reasons set forth above. Furthermore, optimizing the timeframe of transduction would be obvious over the teachings of the ‘272 publication and the ‘649 publication for the same reasons set forth above. Furthermore, it would be obvious to use a Tcm with a CD3+CD8+CD62L+CD45A-CD45RO+ phenotype, since both the ‘272 publication teaches a similar culture process for obtaining Tcm with said phenotype wherein they are useful for treating disease, such as a tumor or infection (see page 16, in particular).
Claims 1, 3-5, 9, 13, 25-26, and 30-31 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of US 11,844,827, claims 1-20 of 12,508,307, or claims 1-15 of 11,179,448 , in view of WO 2018/002924 and US 2016/0340649.
The ‘448, ‘307, and '827 patents claim methods of producing Tcm cells that are transduced with a polynucleotide encoding a cell surface receptor comprising a T cell receptor signaling molecule, such as a CAR, or Tcm cells comprising said receptor made by a method, wherein the method for producing the Tcm comprises contacting PBMC comprising T cells with third party antigen or antigens in the presence of IL-21 to allow enrichment of antigen reactive cells, and culturing said cells in the presence of IL-21, IL-15, and IL-7 to allow proliferation of anti-third party cells comprising a Tcm phenotype, wherein the cells are tolerance inducing cells and wherein the Tcm phenotype comprises CD3+CD8+CD62L+CD45RA-CD45RO+ phenotype. The patents claims that the CAR comprises a CD3 signaling domain and a costimulatory domain, and that the CAR binds to a tumor antigen or a viral antigen and that the method is performed ex-vivo. The patents claims that the Tcm are tolerance inducing cells (i.e. veto cells).
Although the patents do not specifically claim that the starting T cell population comprises at least 40% memory CD8+ T cells, it would be obvious to do so based on the teachings of WO 2018/002924 for the same reasons set forth above. Furthermore, optimizing the timeframe of transduction would be obvious over the teachings of the WO 2018/002924 and the ‘649 publication for the same reasons set forth above.
Applicant argues that the claims are not obvious for the reasons set forth above.
The claims stand rejected for the reasons set forth above.
The following are new grounds of rejection necessitated by Applicant’s claim amendments.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 3-5, 9, 13, 25-26, and 30-31 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The claims are indefinite in the recitation of transducing cells “on days 4-6 of the culture beginning at step b)”. The limitation seems to imply that the transduction should begin on days 4-6 of the culture of step b). However, the claims also recite that the culture of step b) can be as little as 1 day. Are the claims meant to be interpreted as performing the transduction on days 4-6 of culture, wherein day 0 of culture is the first day of culturing in step b)? The scope of the claims unclear and indefinite because it is not clear if the claims encompass transducing during step c) or whether they are meant to require transduction beginning on days 4-6 of the culture of step b).
The following is a quotation of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 3-5, 9, 13, 25-26, and 30-31 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
The specification and the claims as originally filed do not provide support for the invention as now claimed, specifically:
A method comprising transducing with a polynucleotide encoding a heterologous cell surface receptor comprising “an extracellular domain directed against a disease antigen” (Claim 1, and dependent claims).
Applicant indicates that support for the new limitations of Claim 1 can be found at page 21 of the specification.
A review of the specification fails to reveal support for the new limitations.
At page 21 the specification discloses that CAR comprise an extracellular antigen binding moiety, and that it can bind an antigen that acts a cell surface marker on target cells associated with a particular disease state.
However, the present claims are much broader, and encompass any heterologous cell surface receptor, having an extracellular antigen domain, and not just a CAR, which is the support cited. For example, a CAR has a particular type of art-recognized structure with an extracellular antigen binding domain. But the claims are not limited to a CAR, and encompass any heterologous cell surface receptor with an extracellular domain directed against any disease antigen, which is broader than what is disclosed in the specification and would encompass non-CAR structures, for example. Furthermore, the CAR are disclosed to have an extracellular “antigen binding domain” against a “cell surface marker on target cell associated with a disease state”, which is narrower than what is encompassed in the present claims which encompass any extracellular domain directed against any disease antigen. For example, the present claims would encompass soluble disease antigens.
No claim is allowed.
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 extension fee 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 date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY E JUEDES whose telephone number is (571)272-4471. The examiner can normally be reached on M-F from 7am to 3pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached on 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Amy E. Juedes
Patent Examiner
Technology Center 1600
/AMY E JUEDES/Primary Examiner, Art Unit 1644
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