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 .
Priority
This application is a U.S. national phase of International Application No. PCT/CN2021/113520, filed on 08/19/2021. This application claims priority to PEOPLE'S REPUBLIC OF CHINA Application No. CN202010760483.0, filed 07/31/2020. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Status
The amendment, filed on 01/13/2023, in which claims 3-5, 7-9, 12, and 15-16 are amended; claims 10-11 and 17 are canceled; and claims 18-23 are new, is acknowledged. Claims 1-9, 12-16, and 18-23 are pending in the instant application and are examined on the merits herein.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 01/13/2023 and 06/07/2023 have been considered by the examiner.
Specification
The disclosure is objected to because of the following informalities:
¶ [00023], line 2; ¶ [00083], line 2 - “Graves disease” should read “Graves’ disease”
¶ [00028], line 8 - “i,e.” should read “i.e.”
¶ [00031], line 4 - spaces missing between “LTβbinds" and “LTαto"
Appropriate correction is required.
The use of the terms:
“Ficoll” (¶ [00063], second to last line)
“Opti-MEM” (¶ [00096], line 1)
“X-tremeGENE” (¶ [00096], line 5)
“DynaBeads” (¶ [00097], line 1)
“AffiniPure” (¶ [00098], line 2)
“Trucount” (¶ [000115], line 3)
which are trade names or marks used in commerce, have been noted in this application. Each term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
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 Rejections - 35 USC § 112(b)
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 2 and 19-23 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.
Regarding claim 2, the instant claim recites the CD94 intracellular region, as disclosed in base claim 1, has at least 90% identity to SEQ ID NO: 25. However, the sequence disclosed therein encodes a CD94 extracellular domain (identical to residues 32-179 of Human KLRD1; UniProt Q13241 - alignment shown below) making the scope of a “CD94 intracellular region” unclear.
Human KLRD1 (CD94; residues 32-179) alignment with Instant SEQ ID NO:25:
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498
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Human KLRD1 (CD94) sequence topology according to residues:
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499
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Regarding claims 19-23, the instant claims are rejected by virtue of their dependency on claim 2 as they do not rectify the ambiguity as discussed above.
In the instant office action, examiner has interpreted claim 1 to refer the intracellular domain of CD94 comprising amino acids 1-10 of human KLRD1 (i.e. amino acid sequence “MAVFKTTLWR”).
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)(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, 3-9, and 12-16 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by US 11,560,561 B2 (herein Lim).
Regarding claims 1, 3-7, 9, and 12-13, Lim teaches modular protein receptors/chimeric antigen receptor (CAR) (claims 2 and 4) wherein the receptor comprises an antigen binding domain, a transmembrane domain (TMD), and an intracellular signaling domain (claim 3). Of these modular CARs, Lim teaches 62 known co-modulatory domains including CD94 intracellular domain (FIG.4, index 43; SEQ ID NO: 61). Lim teaches one-dimensional (single co-modulatory domain) or two-dimensional (two co-modulatory domains) CAR screening libraries wherein the modules in a classical CAR (scFv, TMD, coregulatory domain, and primary signaling domain) are diversified with different combinations of coregulatory and primary signaling domains (62 members tested including CD94 as disclosed in FIG. 4) (FIG. 5, 7 and 11). Specific libraries were constructed into lentivirus for expression in T-cells (column 78, lines 24-46; claims 6-8) included:
one dimensional libraries including anti-CD19 domain or anti-mesothelin (scFv-TMD) fused to one of the 62 listed co-modulatory domains (e.g. CD94 and other species that overlap with the instant claims), and a CD3ζ-EGFP reporter (column 78, lines 50-54 and 60-63), and
two-dimensional library using an anti-CD19 domain fused to a first co-modulatory domain, a second co-modulatory domain (62-by-62 members; e.g. CD94 and other species that overlap with the instant claims), and a CD3ζ-EGFP reporter (column 78, lines 55-59).
Regarding claim 8, Lim teaches TMD to include CD8α hinge (SEQ ID NO:1), and teaches non-limiting examples of alternative suitable TM sequences derived from CD8β, CD4, CD3ζ, CD28, CD134, or CD7 (SEQ ID NOs: 2-7; column 25-26 spanning ¶).
Regarding claims 14-16, Lim teaches the respective library can be transfected into eukaryotic (claim 6) cells, of which include human T cells (claim 8). Lim further defines human “T cells” (recited in claim 8) to include all types of immune cells expressing CD3 including T-helper cells (CD4+ cells), cytotoxic T-cells (CD8+ cells), T-regulatory cells, and γδ-T cells (column 13, lines 47-50). Lim also teaches suitable eukaryotic cells to include primary cells obtained from an individual (e.g. stem cell or progenitor cell; column 48, ¶ 2 and 4).
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-9, 12-13, 15-16, and 18-23 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2020/097346 A1 (herein McGinness).
Regarding claims 1-2, 12, and 15, McGinness teaches genetically engineered hematopoietic cells which express a CAR comprising extracellular binding domain (anti-GPC3 scFv), transmembrane domain, a cytoplasmic signaling domain, and a costimulatory domain which is a member of the B7/CD28 superfamily, a member of the tumor necrosis factor (TNF) superfamily, or a ligand thereof (claim 1; Table 1). McGinness further teaches the TNF superfamily or ligand thereof is selected from a group that includes LTβ (TNF-C; lymphotoxin beta) (claim 3, line 6; pg. 2, line 22), which comprises a disclosed sequence (SEQ ID NO:66) containing identical amino acids to those recited in instant SEQ ID NO:27 (see alignment below).
Instant SEQ ID NO: 27 (Query) aligned with McGinness SEQ ID NO:66 (Subject):
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While McGinness does not explicitly generate a polypeptide comprising a CAR comprising an LTβ costimulatory domain, it would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention to substitute the CD27, CD70, LIGHT, or OX40L in the constructs explicitly demonstrated (i.e. Figures 1-10) with LTβ (comprising identical amino acids as discussed above) based on the disclosure of McGinness. An ordinarily skilled artisan would have been able to make this substitution with a reasonable expectation of success as McGinness teaches LTβ as an alternative costimulatory peptide to CD70, LIGHT, or OX40.
Regarding claims 3-9, 13, and 19-23, McGinness teaches claim 1 and 2 as discussed above. McGinness further teaches base CAR constructs transfected into T cells either alone or in combination with costimulatory peptide (pg. 70, lines 3-13; separated by a P2A sequence - pg. 71, line 1). These base CARs include species recited in the instant claims: 4-1BB or CD28 costimulatory domain, anti-GPC3 scFv antigen binding domain, CD8 or CD28 transmembrane domain, and CD3ζ cytoplasmic signaling domain (summarized in Table 1 shown below; SEQ ID NO:1 and SEQ ID NO:2, respectively).
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Regarding claims 16 and 18, McGinness teaches claim 12 as discussed above. McGinness also teaches pharmaceutical compositions comprising engineered hematopoietic cells comprising a TNFSF modified CAR with a pharmaceutically acceptable carrier (claim 35) and teaches methods of treating cancer (associated with GPC3 antigen expression) using said compositions (claims 35-40) as demonstrated in xenograft mouse models, which show enhanced anti-tumor activity as compared with base CARs alone (i.e. without additional TNFSF members) (Examples 8-9, pg. 78-80; Figures 7 and 8).
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.
US 18/020,319
Claims 1, 3-9, 12-16, and 18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6-12, 16-18, 24, and 26 of copending Application No. 18/020,319 (herein US319). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 1 and 12, US319 claims an engineered immune cell expressing a chimeric receptor (claim 1), wherein the chimeric receptor is a chimeric antigen receptor (claim 6), comprising a ligand binding domain, a TMD, costimulatory domain, and an intracellular signaling domain (claim 7), and further claims the co-stimulatory domain is one or more costimulatory domains selected from a group including CD94 and LTB (claim 12). Because US319 claims a species of CAR within scope of the instant claims (and immune cells expressing said CAR(s)), the claims are therefore patentably indistinct.
Regarding claim 3-4 (dependent on claim 1), claim 12 of US319 claims the co-stimulatory domain is one or more of costimulatory domains selected from additional species that overlap those recited in the instant claims including CD27, CD28, CD134, CD137, or CD278.
Regarding claims 5-6 (dependent on claim 1), claim 8 of US319 claims the ligand binding domain is selected from an immunoglobin molecule (e.g. antibody) including antibody species which overlap in scope with the instant claims.
Regarding claim 7 (dependent on claim 1), claim 9 of US319 claims an overlapping species list of ligand binding domain targets.
Regarding claims 8-9 (dependent on claim 1), claims 10 and 11 of US319 claim identical lists of potential species of transmembrane and intracellular signaling domains, respectively.
Regarding claims 13-14 (dependent on claim 12), claim 16 of US319 claims an identical list of immune cells and claim 17 of US319 further claims T cells to include an identical list of species.
Regarding claim 15 (dependent on claim 12), claim 18 of US319 claims the immune cell of claim 1 is derived from an identical list of cell types.
Regarding claim 16 (dependent on claim 12), claim 24 of US319 claims a pharmaceutical composition comprising the patentably indistinct immune cell (as discussed above) and one or more pharmaceutically acceptable excipients.
Regarding claim 18 (dependent on claim 16), claim 26 of US319 claims a method for treating cancers, infections or autoimmune diseases in a subject comprising administering the patentably indistinct immune cells (as discussed above) which overlaps in scope with the intended use as recited in the instant claim.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are currently allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HANNAH SUNSHINE whose telephone number is (571)270-7417. The examiner can normally be reached M-Th & Second Friday 8:30am-5pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached at (571) 272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/HANNAH SUNSHINE/Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647