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 .
The amendment to the claims filed on 5/29/2026, does not comply with the requirements of 37 CFR 1.121(c) because the claims are not properly marked-up. Amendments to the claims filed on or after July 30, 2003 must comply with 37 CFR 1.121(c) which states (emphasis added):
(c) Claims. Amendments to a claim must be made by rewriting the entire claim with all changes (e.g., additions and deletions) as indicated in this subsection, except when the claim is being cancelled. Each amendment document that includes a change to an existing claim, cancellation of an existing claim or addition of a new claim, must include a complete listing of all claims ever presented, including the text of all pending and withdrawn claims, in the application. The claim listing, including the text of the claims, in the amendment document will serve to replace all prior versions of the claims, in the application. In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).
(1) Claim listing. All of the claims presented in a claim listing shall be presented in ascending numerical order. Consecutive claims having the same status of “canceled” or “not entered” may be aggregated into one statement (e.g., Claims 1–5 (canceled)). The claim listing shall commence on a separate sheet of the amendment document and the sheet(s) that contain the text of any part of the claims shall not contain any other part of the amendment.
(2) When claim text with markings is required. All claims being currently amended in an amendment paper shall be presented in the claim listing, indicate a status of “currently amended,” and be submitted with markings to indicate the changes that have been made relative to the immediate prior version of the claims. The text of any added subject matter must be shown by underlining the added text. The text of any deleted matter must be shown by strike-through except that double brackets placed before and after the deleted characters may be used to show deletion of five or fewer consecutive characters. The text of any deleted subject matter must be shown by being placed within double brackets if strike-through cannot be easily perceived. Only claims having the status of “currently amended,” or “withdrawn” if also being amended, shall include markings. If a withdrawn claim is currently amended, its status in the claim listing may be identified as “withdrawn—currently amended.”
(3) When claim text in clean version is required. The text of all pending claims not being currently amended shall be presented in the claim listing in clean version, i.e., without any markings in the presentation of text. The presentation of a clean version of any claim having the status of “original,” “withdrawn” or “previously presented” will constitute an assertion that it has not been changed relative to the immediate prior version, except to omit markings that may have been present in the immediate prior version of the claims of the status of “withdrawn” or “previously presented.” Any claim added by amendment must be indicated with the status of “new” and presented in clean version, i.e., without any underlining.
(4) When claim text shall not be presented; canceling a claim.
(i) No claim text shall be presented for any claim in the claim listing with the status of “canceled” or “not entered.”
(ii) Cancellation of a claim shall be effected by an instruction to cancel a particular claim number. Identifying the status of a claim in the claim listing as “canceled” will constitute an instruction to cancel the claim.
(5) Reinstatement of previously canceled claim. A claim which was previously canceled may be reinstated only by adding the claim as a “new” claim with a new claim number.
As noted above, the amendment under consideration herein fails to comply with 37 CFR 1.121 because some text imported from the previous version of claim 100 is underlined. The amendment could be therefore considered non-responsive. In the interest of compact prosecution, the amendment at issue will not be considered non-responsive, however, any future responses failing to comply with 37 CFR 1.121 will be held non-responsive and will not be considered.
Claims 100-116, 118, and 120-134, of record 5/29/2026, are pending and subject to prosecution. Claims 100, 104, and 118 are amended. Claims 117 and 119 are cancelled. Claims 126-134 are newly added.
Status of Prior Rejections/Response to Arguments
RE: Objection to the specification:
The submission of a substitute specification is effective to obviate the objection. The objection is withdrawn.
RE: Objection to claims 100, 117, and 124:
The cancellation of claim 117 renders the objection thereto moot.
The amendment to claims 100 and 124 is effective to obviate the objection. The objection is withdrawn.
RE: Rejection of claims 100-118 and 120-125 under 35 U.S.C. 112(b):
The cancellation of claim 117 renders the rejection thereto moot.
The amendment to claim 100 is effective to obviate the rejection. The rejection is withdrawn.
RE: Rejection of claims 100-101, 108, and 115-118 under 35 U.S.C. 102(a)(1) and 102(a)(2) over Gross et al. (US 20200316120 A1):
RE: Rejection of claims 100-102, 106, 108, and 115-118 under 35 U.S.C. 103 over Gross et al. (US 20200316120 A1) in view of Wu et al. (US 20160185862 A1):
RE: Rejection of claims 100-102, 108-109, and 115-118 under 35 U.S.C. 103 over Gross et al. (US 20200316120 A1) in view of Liu et al. (CN 109504696 A, machine translation):
RE: Rejection of claims 100-102, 108, 110-111, and 115-118 under 35 U.S.C. 103 over Gross et al. (US 20200316120 A1) in view of Pule et al. (US 20160289293 A1):
RE: Rejection of claims 100-102, 108, 115-118, and 120-124 under 35 U.S.C. 103 over Gross et al. (US 20200316120 A1) in view of Zhao et al. (US 20170290858 A1):
The cancellation of claim 117 renders the rejections thereto moot.
The amendment to claim 100 to require LILRB1 hinge, transmembrane, and intracellular domains is effective to obviate the rejections. The rejections are withdrawn.
RE: Rejection of claims 100-104, 106, 108-113, 115-118, 120, and 122-123 on the ground of nonstatutory double patenting over claims 1-4, 8-10, 15-19 of U.S. Patent No. 11602543:
The cancellation of claim 117 renders the rejection thereto moot.
The terminal disclaimer filed on 5/29/2026 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of US Patent No. 11602543 has been reviewed and is accepted. The terminal disclaimer has been recorded. The rejection is withdrawn.
RE: Provisional rejection of claims 100-101, 106, 108, 115, 117-118, and 120 on the ground of nonstatutory double patenting over claims 97-98, 105, 107, 111-112, and 114-115 of co-pending Application No. 18833321:
The cancellation of claim 117 renders the rejection thereto moot.
The applicant has traversed the provisional rejection on the ground that the instant application has an earlier patent term filing date (Applicant Remarks, page 12).
The applicant’s argument is not persuasive, as no claims in the instant application have been allowed. The provisional rejection is maintained in modified form to address amended limitations.
New/Maintained Rejections
Claim Interpretation
Claim 100 recites the limitation “wherein the… LILRB1 intracellular domain comprises a sequence of SEQ ID NO: 71, or a sequence having at least 90% identity thereto”. The broadest reasonable interpretation of “a sequence of SEQ ID NO: 71” is considered to be any sequence comprising two or more sequential amino acids of instant SEQ ID NO 71.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 110 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 110 recites the limitation “wherein the second receptor comprises a leukocyte immunoglobulin like receptor B1 (LILRB1) intracellular domain or a functional variant thereof”. Because parent claim 100 requires a LILRB1 intracellular domain, claim 110 improperly broadens the scope of claim 100.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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, 108, 110-111, 115-116, and 118 are rejected under 35 U.S.C. 103 as being unpatentable over Gross et al. (US 20200316120 A1), of record, in view of Li (US 20220332786 A1), Pule et al. (US 20160289293 A1), of record, Guedan et al. (Molecular Therapy Advances, 2019), of record in IDS dated 7/8/2026, and Wang et al. (Cellular & Molecular Immunology, 2019).
Regarding claims 100-102, 108, 110-111, 115, and 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.
Gross et al. do not expressly teach the inhibitory CAR as comprising LILRB1 hinge, transmembrane, and intracellular domains.
Li teaches that CAR transmembrane and intracellular signaling domains can be derived from molecules such as LILRB1 (See ¶0047 and 0053).
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 (which also contained within instant SEQ ID NO 71 and therefore reads on “comprises a sequence of SEQ ID NO: 71”) (See ¶0198 and 0200-0201, SEQ ID NO 24, and alignment to instant SEQ ID NO 71 below). This sequence also comprises the sequences of instant SEQ ID NOs 56-59 (underlined).
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Guedan et al. teach that the majority of CARs are designed with Ig-like domain hinges (See page 146, col. 2, ¶3).
Wang et al. teach that LILRB1 comprises an extracellular domain with Ig-like domains (See Abstract; page 967, col. 1, full ¶1; and fig. 1).
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 LILRB1-derived transmembrane and intracellular domains, including the intracellular domain taught by Pule et al. One would be motivated to make this modification because Li et al. teach that CARs can comprise a LILRB1 transmembrane domain and endodomain (See ¶0047 and 0053) and because Pule et al. particularly 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.
It would have been further obvious to include a LILRB1-derived hinge in the construct because Wang et al. teach that LILRB1 comprises Ig-like domains (See Abstract; page 967, col. 1, full ¶1; and fig. 1) and Guedan et al. teach that Ig-like domains are typically used as CAR hinges (See page 146, col. 2, ¶3). One or more LILRB1 Ig-like domains could be readily inserted into the inhibitory CAR construct of Gross et al. as a hinge.
Regarding claim 116: Following the discussion of claims 100-102, 108, 110-111, 115, and 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).
Claims 100-102, 106, 108, 110-111, 115, and 118 are rejected under 35 U.S.C. 103 as being unpatentable over Gross et al. (US 20200316120 A1), of record, in view of Li (US 20220332786 A1), Pule et al. (US 20160289293 A1), of record, Guedan et al. (Molecular Therapy Advances, 2019), of record, and Wang et al. (Cellular & Molecular Immunology, 2019), further in view of Wu et al. (US 20160185862 A1), of record.
The teachings of Gross et al., Li, Pule et al., Guedan et al., and Wang 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, 110-111, 115-116, and 118, Gross et al., modified by Li, Pule et al., Guedan et al., and Wang et al., render obvious 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 mesothelin-targeting CAR of Gross et al., modified by Li, Pule et al., Guedan et al., and Wang 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. with a reasonable expectation of success.
Claims 100-102, 108, 110-112, 115, and 118 are rejected under 35 U.S.C. 103 as being unpatentable over Gross et al. (US 20200316120 A1), of record, in view of Li (US 20220332786 A1), Pule et al. (US 20160289293 A1), of record, Guedan et al. (Molecular Therapy Advances, 2019), of record, and Wang et al. (Cellular & Molecular Immunology, 2019), further in view of Colonna et al. (Journal of Experimental Medicine, 1997).
The teachings of Gross et al., Li, Pule et al., Guedan et al., and Wang et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claim 112: Following the discussion of claims 100-102, 108, 110-111, 115-116, and 118, Gross et al., modified by Li, Pule et al., Guedan et al., and Wang et al., render obvious an activating CAR targeting mesothelin and an inhibitory LILRB1-derived CAR targeting HLA. Li teaches a LILRB1 transmembrane domain but does not expressly teach the sequence of SEQ ID NO 74.
Colonna et al. teach the sequence of the ILT2 (which reads on “LILRB1”) transmembrane domain as LGVVIGILVAVILLLLLLLLLFLI, which comprises the sequence of instant SEQ ID NO 74 (See fig. 9 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 inhibitory CAR rendered obvious by Gross et al., modified by Li, Pule et al., Guedan et al., and Wang et al., to substitute the LILRB1 transmembrane domain sequence taught by Colonna 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). Such a modification to the CAR transmembrane domain could be readily performed.
Claims 100-102, 108, 115-116, 118, and 120-124 are rejected under 35 U.S.C. 103 as being unpatentable over Gross et al. (US 20200316120 A1), of record, in view of Li (US 20220332786 A1), Pule et al. (US 20160289293 A1), of record, Guedan et al. (Molecular Therapy Advances, 2019), of record, and Wang et al. (Cellular & Molecular Immunology, 2019), further in view of Zhao et al. (US 20170290858 A1).
The teachings of Gross et al., Li, Pule et al., Guedan et al., and Wang 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, 110-111, 115-116, and 118, Gross et al., modified by Li, Pule et al., Guedan et al., and Wang et al., render obvious an activating CAR targeting mesothelin and an inhibitory LILRB1-derived 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., modified by Li, Pule et al., Guedan et al., and Wang 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 a 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. 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 100-101, 103, 105-106, 108, 115, 118, and 120 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 97-98, 102, 104-105, 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, 108, and 115: 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 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. Co-pending claim 108 recites the immune cell of co-pending claim 107, wherein the LILRB1 hinge domain, LILRB1 intracellular domain and LILRB 1 transmembrane domain comprises SEQ ID NO: 71 or a sequence at least 90%, at least 95%, at least 97%, at least 99% or is identical to SEQ ID NO: 71 (which also reads on “wherein the LILRBI intracellular domain comprises immunoreceptor tyrosine-based inhibitory motifs (ITIMs) NLYAAV (SEQ ID NO: 56), VTYAEV (SEQ ID NO: 57), VTYAQL (SEQ ID NO: 58), and SIYATL (SEQ ID NO: 59)”). 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 103: Following the discussion of claims 100-101, 108, and 115, co-pending claim 102 recites the immune cell of co-pending claim 97, wherein the extracellular ligand binding domain of the first receptor comprises complementarity determining regions (CDRs) CDR-L1, CDR-L2, CDR- L3, CDR-H1, CDR-H2, CDR-H3 as disclosed Table 2. Table 2 includes SEQ ID NOs 438, 454, and 488 as CDR-H1, CDR-H2, and CDR-H3 regions, respectively, and SEQ ID NOs 535, 539, and 542 as CDR-L1, CDR-L2, and CDR-L3 regions, respectively. The co-pending claim renders obvious the instant claim.
Regarding claim 105: Following the discussion of claims 100-101, 108, and 115, co-pending claim 104 recites the immune cell of co-pending claim 97, wherein the extracellular ligand binding domain of the first receptor comprises a variable heavy (VH) portion comprising SEQ ID NO: 233 or a sequence having at least 85%, at least 90%, at least 95%, at least 97%, or at least 99% identity thereto, and a variable light (VL) portion comprising SEQ ID NO: 279 or a sequence having 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 106: Following the discussion of claims 100-101, 108, and 115, 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 claims 118: Following the discussion of claims 100-101, 108, and 115, 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, 108, and 115, 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 104, 107, 113-114, and 125-134 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 34 (or a sequence at least 85% identical thereto); 71 (or a sequence at least 95% identical thereto); 42, 44-47, and 1256; 66-67 or 81 (or a sequence at least 85% identical thereto); 89 (or a sequence at least 85% identical thereto); or 349 or 350 appear to be free of the prior art.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to 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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/J.S.S./Examiner, Art Unit 1633
/CHRISTOPHER M BABIC/Supervisory Patent Examiner, Art Unit 1633
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