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 .
Applicant’s amendments to the claims dated 10/28/2025 are acknowledged. Claims 1-99 are cancelled. Claims 100-125 are newly added.
Election/Restrictions
Applicant’s election without traverse of group II in the reply filed on 10/28/2025 is acknowledged. New claims 100-118 and 120-125, of record 10/28/2025, read on the elected invention and are subject to prosecution.
Claim 119 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/28/2025.
Priority
The instant application is a CON of 17/662766 (US 11602543 B2, filed 5/10/2022), which is a CON of PCT/US2021/046751 (filed 8/19/2021), which claims benefit of provisional application 63/068245 (filed 8/20/2020). Acknowledgement is also made of the applicant’s claim for benefit to provisional application 63/085971 (filed 9/30/2020).
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the claims are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Claim 104 recites a CDR-L2 having the sequence KVSNRFSGVPAR. All sequences longer than ten nucleotides or four amino acids referenced in the specification must include a SEQ ID NO and must be included in the Sequence Listing. See MPEP 2421-2422.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the disclosure, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code in ¶0686 of the instant specification’s PG Pub. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP 608.01.
The use of the terms X-VIVO, Dynabeads, OpTmizer, CytoMate, Cell Saver, Neon, ONE-Step, LymphoOne, TransAct, MACS, Geneticin, FACSCanto, QIFIKIT, HuTARG, VERSENE, AlexaFluor, TrypLE, 4D-Nucleofector, Matrigel, XenoLight, Nucleocuvette, GraphPad, and Prism, which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 100, 117, and 124 are objected to because of the following informalities:
Each claim must begin with a capital letter and end with a period. Periods may not be used elsewhere in the claims except for abbreviations. See MPEP 608.01(m).
Appropriate correction is required.
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.
Claims 100-118 and 120-125 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.
Claim 100 recites the limitations "the first receptor" and “the second receptor” in lines 6-7. There is insufficient antecedent basis for these limitations in the claim. Dependent claims 101-118 and 120-125 are included in the rejection because they depend from a rejected claim.
Claim Rejections - 35 USC § 102
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 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 100-101, 108, and 115-118 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Gross et al. (US 20200316120 A1).
Gross et al. teach synthetic receptor pairs comprised of an inhibitory CAR directed to a polymorphic surface epitope and an activating CAR directed to a non-polymorphic surface epitope (See Abstract).
Regarding claims 100-101, 108, 115, and 117-118: Gross et al. teach the pairing and use of an activating CAR that targets mesothelin and an inhibitory CAR that targets HLA (See ¶0096, 0099, and 0382-0385). The inhibitory CAR targets a single allelic variant lost from tumor cells due to loss of heterozygosity of the chromosomal region it resides in (which reads on “a non-target antigen lost in a… cancer cell”), while the allelic variant remains expressed in normal cells (See ¶0215). The HLA gene can be an HLA-A, HLA-B, or HLA-C gene and can be HLA-A2 (which reads on “HLA-A*02”) in specific embodiments (See ¶0033-0036, 0244, and 0483). Both CARs can be expressed by the same vector (which reads on “a polynucleotide”) or different vectors (See ¶0083-0084). The CARs comprise scFvs fused through a flexible hinge and transmembrane domain to intracellular signaling components (which reads on “intracellular domain”) (See ¶0006). Gross et al. therefore disclose a polynucleotide or polynucleotides encoding a first activator receptor polypeptide comprising a mesothelin-specific extracellular ligand binding domain and a second inhibitory receptor polypeptide comprising an extracellular ligand binding domain specific for HLA variants which are lost in tumor cells.
Regarding claim 116: Following the discussion of claims 100-101, 108, 115, and 117-118, Gross et al. teach that the nucleic acid compositions can be formulated with physiological carriers or excipients and that the compositions can be used in therapeutically effective amounts (See ¶0120 and 0208-0210).
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 100-102, 106, 108, 115-118 are rejected under 35 U.S.C. 103 as being unpatentable over Gross et al. (US 20200316120 A1) in view of Wu et al. (US 20160185862 A1).
The teachings of Gross et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claim 106: Following the discussion of claims 100-102, 108, and 115-118, Gross et al. teach an activating CAR targeting mesothelin and an inhibitory CAR targeting HLA but do not expressly teach the sequence of instant SEQ ID NO 171.
Wu et al. teach CARs targeting mesothelin comprising an scFv having a sequence 94.2% identical to the sequence of instant SEQ ID NO 171 (See fig. 23A, SEQ ID NO 136, and alignment below (first 120 aa displayed)).
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It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Gross et al. to substitute the mesothelin-specific scFv taught by Wu et al. Simple substitution of one known element for another equivalent known element is considered to be prima facie obvious, absent a showing that the substitution yields more than predictable results. See MPEP 2143(I)(B). One of ordinary skill in the art could therefore substitute the scFv of Wu et al. in the method of Gross et al. with a reasonable expectation of success.
Claims 100-102, 108-109, 115-118 are rejected under 35 U.S.C. 103 as being unpatentable over Gross et al. (US 20200316120 A1) in view of Liu et al. (CN 109504696 A, machine translation).
The teachings of Gross et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claim 109: Following the discussion of claims 100-102, 108, and 115-118, Gross et al. teach an activating CAR targeting mesothelin and an inhibitory CAR targeting HLA but do not expressly teach the sequence of instant SEQ ID NO 303.
Liu et al. teach a CAR targeting human mesothelin comprising a sequence 91.7% identical to the sequence of instant SEQ ID NO 303 (See Abstract, SEQ ID NO 2, and alignment below (first 120 aa displayed)).
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It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Gross et al. to substitute the mesothelin-specific CAR taught by Liu et al. Simple substitution of one known element for another equivalent known element is considered to be prima facie obvious, absent a showing that the substitution yields more than predictable results. See MPEP 2143(I)(B). One of ordinary skill in the art could therefore substitute the CAR of Liu et al. in the method of Gross et al. with a reasonable expectation of success.
Claims 100-102, 108, 110-111, 115-118 are rejected under 35 U.S.C. 103 as being unpatentable over Gross et al. (US 20200316120 A1) in view of Pule et al. (US 20160289293 A1).
The teachings of Gross et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claims 110-111: Following the discussion of claims 100-102, 108, and 115-118, Gross et al. teach an activating CAR targeting mesothelin and an inhibitory CAR targeting HLA but do not expressly teach the inhibitory CAR as comprising a LILRB1 intracellular domain.
Pule et al. teach CAR pairs comprising an activating receptor and an inhibitory receptor (See Abstract). The inhibitory CAR can comprise an LILRB1 endodomain sequence identical to the sequence of instant SEQ ID NO 70 (See ¶0198 and 0200-0201, SEQ ID NO 24, and alignment below (first 120 aa displayed)).
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It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the inhibitory CAR of Gross et al. to comprise the intracellular domain taught by Pule et al. One would be motivated to make this modification because Pule et al. teach LILRB1-derived signaling domains as appropriate for inhibitory CARs (See ¶0198). There would be a reasonable expectation of success in doing so because use of this LILRB1-derived sequence in CARs was known at the time of the invention, and it could be readily inserted into the CAR construct of Gross et al.
Claims 100-102, 108, 115-118, and 120-124 are rejected under 35 U.S.C. 103 as being unpatentable over Gross et al. (US 20200316120 A1) in view of Zhao et al. (US 20170290858 A1).
The teachings of Gross et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claims 120-124: Following the discussion of claims 100-102, 108, and 115-118, Gross et al. teach an activating CAR targeting mesothelin and an inhibitory CAR targeting HLA but do not expressly teach a polynucleotide encoding a B2M shRNA.
Zhao et al. teach methods for inhibiting expression of endogenous T cell genes, including B2M, using nucleic acids (See Abstract). The nucleic acid can be an shRNA (See ¶0018 and 0244). Zhao et al. teach a gRNA sequence for targeting B2M identical to the sequence of instant SEQ ID NO 894 (See ¶0399, SEQ ID NO 3, and alignment below).
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It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the CAR-expressing cells of Gross et al. to comprise an inhibitory RNA targeting B2M, such as is taught by Zhao et al. One would be motivated to make this modification because Zhao et al. teach that depletion of B2M expression is associated with reduced immunogenicity (See ¶0239), and B2M could be readily knocked down or out in the CAR-expressing cells. One would also be motivated to use the gRNA sequence taught by Zhao et al. in an shRNA molecule because the results of Zhao et al. suggest that this targeting sequence is suitable for inhibiting expression of B2M (See fig. 9). One of ordinary skill would have a reasonable expectation of success in making this modification because the design of shRNA molecules for a given targeting sequence is well characterized in the art, and the use of such a targeting sequence would read on “the sequence that binds the B2M mRNA sequence is complementary to a sequence… identical to any of SEQ ID NOs: 894-1007”.
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 100-104, 106, 108-113, 115-118, 120, and 122-123 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 8-10, 15-19 of U.S. Patent No. 11602543. Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons.
Regarding claims 100-103, 115, and 117: Patented claim 1 recites an immune cell comprising: (a) an activator receptor comprising an extracellular ligand binding domain specific to a Mesothelin (MSLN) antigen, wherein the extracellular ligand binding domain of the activator receptor comprises an scFv comprising (i) a heavy chain variable region (VH) comprising a complementarity determining region (CDR)-H1 of SEQ ID NO: 438, a CDR-H2 of SEQ ID NO: 454, and a CDR-H3 of SEQ ID NO: 533; and (ii) a variable light chain region (VL) comprising a CDR-L1 of SEQ ID NO: 535, a CDR-L2 of SEQ ID NO: 539, and a CDR-L3 of SEQ ID NO: 542; and (b) an inhibitory receptor specific to an HLA-A*02 antigen. Patented claim 16 recites a polynucleotide system comprising one or more polynucleotides comprising polynucleotide sequences encoding (a) an activator receptor comprising an extracellular ligand binding domain specific to a MSLN antigen, wherein the extracellular ligand binding domain of the activator receptor comprises an scFv comprising (i) a VH comprising a CDR-H1 of SEQ ID NO: 438, a CDR-H2 of SEQ ID NO: 454, and a CDR-H3 of SEQ ID NO: 533; and (ii) a VL comprising a CDR-L1 of SEQ ID NO: 535, a CDR-L2 of SEQ ID NO: 539, and a CDR-L3 of SEQ ID NO: 542; and (b) an inhibitory receptor comprising specific to an HLA-A*02 antigen. Patented claim 19 recites a method of treating a MSLN+ cancer in a subject identified as having or suspected of having a loss of heterozygosity at an allele encoding a HLA-A*02 antigen in the MSLN-positive cancer, comprising administering to the subject the immune cells of patented claim 1. The combined limitations of the patented claims render obvious the instant claims.
Regarding claim 104: Following the discussion of claims 100-103, 115, and 117, patented claim 4 recites the immune cell of claim 1, wherein the inhibitory receptor comprises an scFv comprising (i) a VH comprises a CDR-H1 of SEQ ID NO: 45, a CDR-H2 of SEQ ID NO: 46, and a CDR-H3 of SEQ ID NO: 47; and (ii) a VL comprising a CDR-L1 of SEQ ID NO: 42, a CDR-L2 of SEQ ID NO: 43, and a CDR-L3 of SEQ ID NO: 44. The patented claim renders obvious the instant claim.
Regarding claim 106: Following the discussion of claims 100-103, 115, and 117, patented claim 2 recites the immune cell of patented claim 1, wherein the scFv of the activator receptor comprises a sequence having at least 95% identity to the sequence of SEQ ID NO: 171. Patented claim 3 recites the immune cell of patented claim 1, wherein the scFv of the activator receptor comprises the sequence of SEQ ID NO: 171. The patented claims render obvious the instant claim.
Regarding claim 108: Following the discussion of claims 100-103, 115, and 117, patented claim 8 recites the immune cell of patented claim 1, wherein the activator receptor is a chimeric antigen receptor (CAR) comprising a hinge sequence isolated or derived from CD8, a transmembrane domain isolated or derived from CD8, and an intracellular domain isolated or derived from CD28, 4-1BB or CD3z, or a combination thereof. The patented claim renders obvious the instant claim.
Regarding claim 109: Following the discussion of claims 100-103, 108, 115, and 117, patented claim 9 recites the immune cell of patented claim 8, wherein the CAR comprises the sequence of SEQ ID NO: 303. The patented claim renders obvious the instant claim.
Regarding claim 110-113: Following the discussion of claims 100-103, 115, and 117, patented claim 10 recites the immune cell of claim 1, wherein the inhibitory receptor comprises a CAR comprising a LILRB1 intracellular domain, a LILRB1 hinge domain, and a LILRB1 transmembrane domain. Patented claim 11 recites the immune cell of claim 10, wherein the CAR comprises the sequence of SEQ ID NO: 348. SEQ ID NO 348 comprises the sequences of SEQ ID NO 66, 70, and 74 (See underlined sequences in alignment below). The patented claims render obvious the instant claims.
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Regarding claim 116: Following the discussion of claims 100-103, 115, and 117, patented claim 15 recites a pharmaceutical composition, comprising a therapeutically effective amount of the immune cells of patented claim 1 and a pharmaceutically acceptable carrier, diluent or excipient. Because the immune cells necessarily comprise the polynucleotide(s), the patented claim renders obvious the instant claim.
Regarding claim 118: Following the discussion of claims 100-103, 115, and 117, patented claim 18 recites a vector comprising the polynucleotide system of patented claim 16. The patented claim renders obvious the instant claim.
Regarding claims 120 and 122-124: Following the discussion of claims 100-103, 115, and 117, patented claim 17 recites polynucleotide system of claim 16, comprising a sequence encoding an shRNA specific to B2M (which reads on “capable of inducing RNAi-mediated degradation of the B2M mRNA” and “a first sequence, having from 5′ end to 3′ end a sequence complementary to a sequence of the B2M mRNA sequence; and b. a second sequence, having from 5′ end to 3′ end a sequence complementary to the first sequence, wherein the first sequence and the second sequence form the shRNA”). The patented claim renders obvious the instant claims.
Claims 100-101, 1006, 108, 115, 117-118, and 120 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 97-98, 105, 107, 111-112, and 114-115 of co-pending Application No. 18833321 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons.
Regarding claims 100-101, 115, and 117: Co-pending claim 97 recites an immune cell comprising: a. a first receptor, comprising an extracellular ligand binding domain specific to Mesothelin (MSLN); and b. a second receptor, comprising an extracellular ligand binding domain specific to HLA-A*03, wherein the first receptor is an activator receptor responsive to MSLN; and wherein the second receptor is an inhibitory receptor responsive to HLA-A*03. Co-pending claim 98 recites the immune cell of co-pending claim 97, wherein the HLA-A*03 is lost in the MSLN+ cancer cell through loss of heterozygosity. Co-pending claim 114 recites a polynucleotide or polynucleotide system, comprising one or more polynucleotides comprising polynucleotide sequences encoding the first receptor and the second receptor for use in generating the immune cell of claim 97. The combined limitations of the co-pending claims render obvious the instant claims.
Regarding claim 106: Following the discussion of claims 100-101, 115, and 117, co-pending claim 105 recites the immune cell of co-pending claim 97, wherein the extracellular ligand binding domain of the first receptor comprises an scFv sequence of SEQ ID NO: 171; or a sequence having at least 85%, at least 90%, at least 95%, at least 97% or at least 99% identity thereto. The co-pending claim renders obvious the instant claim.
Regarding claim 108: Following the discussion of claims 100-101, 115, and 117, co-pending claim 107 recites the immune cell of co-pending claim 97, wherein the second receptor comprises a LILRB1 intracellular domain, a LILRB1 transmembrane domain, a LILRB1 hinge domain, a functional variant of any of these, or combinations thereof. The co-pending claim renders obvious the instant claim.
Regarding claims 118: Following the discussion of claims 100-101, 115, and 117, co-pending claim 115 recites a vector, comprising the one or more polynucleotides of co-pending claim 114. The co-pending claim renders obvious the instant claim.
Regarding claim 120: Following the discussion of claims 100-101, 115, and 117, co-pending claim 111 recites the immune cell of co-pending claim 97, wherein expression and/or function of a MHC Class I gene has been reduced or eliminated. Co-pending claim 112 recites the immune cell of co-pending claim 111, further comprising a polynucleotide comprising an interfering RNA, the interfering RNA comprising a sequence complementary to a sequence of a B2M mRNA. The co-pending claims render obvious the instant claim.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Allowable Subject Matter
Claims 107, 114, and 125 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
One or more polynucleotides encoding a mesothelin-specific activating receptor and an inhibitory receptor specific for a non-target antigen lost in a mesothelin-positive cancer cell comprising sequences comprising instant SEQ ID NOs 89 (or a sequence at least 85% identical thereto), 171 (or a sequence at least 85% identical thereto), and 349 or 350 appear to be free of the prior art.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER S SPENCE, whose telephone number is 571-272-8590. The examiner can normally be reached M-F 8:30-5:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Christopher M Babic, can be reached at 571-272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.S.S./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633