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 .
Claims 1-43, 46, 54, and 56 are pending in the instant application.
Applicant’s election without traverse of the invention of group I, drawn to cells comprising recombinant cytokine signaling complexes, and the species of induced pluripotent stem cells (iPSCs) expressing a fusion protein of IL7 and IL7Ralpha, having a CD38 knockout as an additional genetic modification, and expressing a single chain CAR specific to MICA/B in the reply filed on June 25, 2026 is acknowledged.
Claims 7, 8, 10, 11, 16-33, 36-43, 46, 54, and 56 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species or invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on June 25, 2026.
Claims 1-6, 9, 12-15, 34, and 35 are under examination as they read upon the elected species of induced pluripotent stem cells (iPSCs) expressing a fusion protein of IL7 and IL7Ralpha, having a CD38 knockout as an additional genetic modification, and expressing a single chain CAR specific to MICA/B
Information Disclosure Statement
The IDS forms received 10/27/2023 and 6/25/2026 are acknowledged and the references cited therein have been considered.
Claim Rejections - 35 USC § 112
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.
Claim 5 is 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.
Dependent claim 5 recites that “one or more of” a list of limitations are to be incorporated into the cell product of claim 1. One recited element in the list is “at least one of the genotypes listed in Table 1”. As per MPEP 2173.05(s), reciting a table in a claim “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.” Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted). Given that a genotype is words, the applicable standard does not appear to have been met. Removal of the table from the claim is suggested.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-6, 9, 12-15, 34, and 35 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2019/112899 (of record).
The ‘899 publication discloses methods of making and compositions comprising induced pluripotent stem cells (iPSC) which express a chimeric antigen receptor (CAR) and express a recombinant cytokine signaling complex comprising an interleukin and its respective receptor (see entire document, particularly the title, abstract, and claims). Notably, paragraph [0012] discloses that a polynucleotide transfected into the cell encodes a partial or full peptide of IL7 and its respective receptor, which is of course IL7R. It is disclosed that adding such constructs to the cells provides cytokine autonomy such that cell growth, proliferation, expansion and/or effector function are maintained or improved while reducing the risk of cytokine toxicity (see particularly paragraph [0157]). It is taught that the working examples disclosed concerning IL15/IL15Ralpha fusion constructs are equally applicable to other cytokines signaling through the common gamma chain, including IL7 (see paragraphs [0157-0168], most particularly [0168]). Notably, the CAR constructs on such cells are disclosed as being single chain, and specific for the MICA/B antigen (see most particularly paragraphs [0022], [0026], and [0149-0156]). Also, a CAR is clearly a type of “chimeric fusion receptor (CFR)” which in addition to the antigen binding ectodomain further comprises endodomains based upon CD3zeta, DAP10 and CD137 which provide for signaling function (see for example paragraph [0151-0154]). Therefore, the prior art anticipates the instant claimed invention.
Claims 1-6, 9, 12-15, 34, and 35 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2019/126748.
The ‘748 publication discloses compositions and methods for making genetically engineered induced pluripotent stem cells (iPSC) that are stable and offer improved or enhanced therapeutic effects (see entire document, particularly the title, abstract, and claims). Such cells are disclosed as being CD38 knockouts (see for example paragraphs [0016], [0121-0124], and [0158-0164], and claim 1) and as comprising a single chain CAR that binds MICA/B (see for example paragraphs [0021] and [0133-0141] and claim 8). Note that a CAR is a type of “chimeric fusion receptor (CFR)” which in addition to the antigen binding ectodomain further comprises endodomains based upon CD3zeta, DAP10 and CD137 which provide for signaling function (see for example paragraph [0135-0141]). Additionally, the iPSC are further disclosed as comprising exogenously induced cytokine signaling complexes which reduce the risk of systemic cytokine toxicity and which comprise fusions of IL7 to IL7Receptor (see particularly paragraphs [0142-0155], most particularly paragraph [0153]). Therefore, the prior art anticipates the instant claimed invention.
Double Patenting
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 1-6, 9, 12-15, 34, and 35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 12,203,098. Although the claims at issue are not identical, they are not patentably distinct from each other because the issued claims anticipate that which has been presently claimed.
The issued claims recite induced pluripotent stem cells (iPSC) expressing a CAR that binds the HER2 antigen and which is defined by SEQ ID numbers for the antigen binding domain of the CAR (see all issued claims, particularly claim 1). Such iPSC are further recited as comprising a CD38 knockout (see particularly claim 12) and as comprising a cytokine signaling complex comprising and IL-7-IL-7R fusion protein (see particularly claim 23). Given that all of the issued claims require the iPSC to express a CAR specific for HER2, the issued claims are narrower in scope, and thus necessarily anticipate, the breadth of iPSC claimed in the instant application.
Claims 1-6, 9, 12-15, 34, and 35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 14-32 and 43-46 of copending Application No. 18/028,457 in view of WO 2019/126748.
The copending claims recite iPSC which are CD38 knockouts and express a chimeric fusion receptor comprising ectodomains, transmembrane domains and endodomains from various unrelated polypeptides (see all copending claims, particularly claims 14 and 15). Such cells are further recited as expressing a CAR that binds the MICA/B antigen (see particularly claim 18) and that expresses exogenous IL-7 and/or IL-7Receptor (see particularly claim 19). Such claims differ from the elected species in that while cytokine signaling complexes comprising IL-15/IL-15R fusion proteins are explicitly recited, IL-7 and its receptor are not explicitly recited as being expressed as a fusion protein.
The ‘748 publication discloses compositions and methods for making genetically engineered induced pluripotent stem cells (iPSC) that are stable and offer improved or enhanced therapeutic effects (see entire document, particularly the title, abstract, and claims). Such cells are disclosed as being CD38 knockouts (see for example paragraphs [0016], [0121-0124], and [0158-0164], and claim 1) and as comprising a single chain CAR that binds MICA/B (see for example paragraphs [0021] and [0133-0141] and claim 8). Note that a CAR is a type of “chimeric fusion receptor (CFR)” which in addition to the antigen binding ectodomain further comprises endodomains based upon CD3zeta, DAP10 and CD137 which provide for signaling function (see for example paragraph [0135-0141]). Additionally, the iPSC are further disclosed as comprising exogenously induced cytokine signaling complexes which reduce the risk of systemic cytokine toxicity and which comprise fusions of IL7 to IL7Receptor (see particularly paragraphs [0142-0155], most particularly paragraph [0153]).
Therefore, it would have been obvious to ordinary artisans that IL:-7/Il-7R signaling complexes could be added to the iPSC of the copending application. Artisans would be motivated to add such signaling complexes to cells in order remove the need for systemic cytokine administration and its attendant risk of toxicity as taught by the ‘748 publication.
This is a provisional nonstatutory double patenting rejection.
Claims 1-6, 9, 12-15, 34, and 35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 8-18, 20, 21, 23-25, 27, 29, and 31-37 of copending Application No. 17/782,600 in view of WO 2019/126748.
The copending claims recite methods of making iPSC which are CD38 knockouts and express a CAR specific for the MICA/B antigen (see all copending claims, particularly claims 1, 3, and 4). Such cells are further recited as expressing exogenous IL-7 and/or IL-7Receptor (see particularly claim 5). Such claims differ from the elected species in that while cytokine signaling complexes comprising IL-15/IL-15R fusion proteins are explicitly recited (see again claim 5), IL-7 and its receptor are not explicitly recited as being expressed as a fusion protein.
The ‘748 publication discloses compositions and methods for making genetically engineered induced pluripotent stem cells (iPSC) that are stable and offer improved or enhanced therapeutic effects (see entire document, particularly the title, abstract, and claims). Such cells are disclosed as being CD38 knockouts (see for example paragraphs [0016], [0121-0124], and [0158-0164], and claim 1) and as comprising a single chain CAR that binds MICA/B (see for example paragraphs [0021] and [0133-0141] and claim 8). Note that a CAR is a type of “chimeric fusion receptor (CFR)” which in addition to the antigen binding ectodomain further comprises endodomains based upon CD3zeta, DAP10 and CD137 which provide for signaling function (see for example paragraph [0135-0141]). Additionally, the iPSC are further disclosed as comprising exogenously induced cytokine signaling complexes which reduce the risk of systemic cytokine toxicity and which comprise fusions of IL7 to IL7Receptor (see particularly paragraphs [0142-0155], most particularly paragraph [0153]).
Therefore, it would have been obvious to ordinary artisans that IL:-7/Il-7R signaling complexes could be added to the iPSC of the copending application. Artisans would be motivated to add such signaling complexes to cells in order remove the need for systemic cytokine administration and its attendant risk of toxicity as taught by the ‘748 publication.
This is a provisional nonstatutory double patenting rejection.
Claims 1-6, 9, 12-15, 34, and 35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14, 22, 23, 29-31, 60, 66, and 87 of copending Application No. 18/854,914. Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims comprise additional limitations and thereby anticipate the breadth of what is presently claimed.
Specifically, the copending claims recite iPSC that comprise a CD38 knockout, a CAR specific for the MICA/B antigen, and an exogenous cytokine signaling complex comprising an IL-7/Il-7R fusion protein (see all copending claims, particularly claims 1, 3, 13, and 14). Such cells are also required to express CXC chemokine receptors, a TGFbeta signaling redirector receptor and an allo-immune defense receptor (see most explicitly copending independent claim 1). Since the copending iPSC are recited as having more limitations as compared to those presently claimed, the copending inventions necessarily anticipates the breadth of the instant claimed inventions.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-6, 9, 12-15, 34, and 35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 45-60 of copending Application No. 18/878,845 in view of WO 2019/126748.
The copending claims recite iPSC which comprise a signaling redirector receptor that comprises a FAS binding domain, are CD38 knockouts, express a CAR, and which express an exogenous cytokine signaling complex comprising an IL-7/IL-7R fusion protein (see all copending claims, particularly claims 45, 46, 52, and 54). Such claims differ from the elected species in that the CAR expressed by the iPSC of the copending claims is not recited as binding the MICA/B antigen.
The ‘748 publication discloses compositions and methods for making genetically engineered induced pluripotent stem cells (iPSC) that are stable and offer improved or enhanced therapeutic effects (see entire document, particularly the title, abstract, and claims). Such cells are disclosed as being CD38 knockouts (see for example paragraphs [0016], [0121-0124], and [0158-0164], and claim 1) and as comprising a single chain CAR that binds MICA/B (see for example paragraphs [0021] and [0133-0141] and claim 8). Note that a CAR is a type of “chimeric fusion receptor (CFR)” which in addition to the antigen binding ectodomain further comprises endodomains based upon CD3zeta, DAP10 and CD137 which provide for signaling function (see for example paragraph [0135-0141]). Additionally, the iPSC are further disclosed as comprising exogenously induced cytokine signaling complexes which reduce the risk of systemic cytokine toxicity and which comprise fusions of IL7 to IL7Receptor (see particularly paragraphs [0142-0155], most particularly paragraph [0153]).
Therefore, it would have been obvious to ordinary artisans that the CAR specificity in the iPSC of the copending claims can be for MICA/B. Artisans would be motivated add such CAR to eth iPSC claimed in the copending application as a CAR has to bind some antigen in order to actually serve as a chimeric antigen receptor, the copending claims recite no specificity for the CAR, and the ‘748 document teaches that CAR specific for MICA/B are to be used in iPSC which also have CD38 knocked out and express fusion proteins comprising IL-7 and IL-7receptor.
This is a provisional nonstatutory double patenting rejection.
Claims 1-6, 9, 12-15, 34, and 35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 6-8, 10-14, 18-28, 33, 34, and 52 of copending Application No. 18/917,836. Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims comprise additional limitations and thereby anticipate the breadth of what is presently claimed.
Specifically, the copending claims recite induced pluripotent stem cells that comprise a CD38 knockout, a CAR specific for the MICA/B antigen, and an exogenous cytokine signaling complex comprising an IL-7/Il-7R fusion protein (see all copending claims, particularly claims 1, 13, and 14). Such cells are also required to express a TGFbeta signaling redirector receptor (see most explicitly copending independent claim 1). Since the copending iPSC are recited as having more limitations as compared to those presently claimed, the copending inventions necessarily anticipates the breadth of the instant claimed inventions.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
No claims are allowable.
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Michael Szperka
Primary Examiner
Art Unit 1641
/MICHAEL SZPERKA/Primary Examiner, Art Unit 1641
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