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 .
1. Claims 1-4, 6, 8-10, 12, 15, 18, 19, 21, 23, 25-27, 29, 32, and 34 are pending and being examined.
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.
2. Claims 2-4, 6, 8-10, 12, 15, 18, 19, 21, 23, 25, 26, 27, 29, 32, and 34 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. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claims 2-4, 6, 9, 10, 12, 15, 18, 19, 21, 23, 26, 27, and 34 recite a broad recitation of features of the immune effector cell, followed by a phrase or several phrases starting with “preferably” which is the narrower statement of the range/limitation of features. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Claims 8, 25, 29, and 32 are rejected for depending on claims reciting “preferably”.
For clarity of record, Examiner interprets all claimed phrases following “preferably” as exemplary or optional.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
3. Claims 1-4, 6, 8-10, 12, 15, 19, 21, 23, 25-27, 29, 32, and 34 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a WRITTEN DESCRIPTION rejection.
The claims are drawn to a multifunctional immune effector cell expressing a protein specifically recognizing FAP and a protein specifically recognizing a tumor-associated antigen. Dependent claims recite the proteins are expressed as a fusion protein. The claims recite the proteins or fusion protein expressed by the multifunctional immune effector cell function to:
Specifically recognize FAP;
Specifically recognize a tumor-associated antigen or a ligand of a tumor antigen;
Specifically recognize tumor-associated antigen Claudin 18.2;
target FAP or a ligand of FAP; and
treat a tumor.
Dependent claims recite a partial protein structure, such as preferably/optionally comprising anti-FAP CDR SEQ ID NOs:35-40 or anti-FAP scFv SEQ ID NO:2; and preferably/optionally comprising anti-CLDN18.2 CDR SEQ ID NOs:26-31 or scFv SEQ ID NO:4. No rejected claims recite and require the shared recognizable sequence structure critical to the claimed functions listed above, that is, the six VH and VL CDR SEQ ID NOs from the protein specifically recognizing FAP and the six VH and VL CDR SEQ ID NOs from the protein specifically recognizing a tumor-associated antigen or Claudin 18.2.
The claims are drawn to a vast genus of multifunctional immune effector cells expressing a vast genus of proteins required to function as listed above.
The published instant specification discloses “tumor-associated antigen” broadly encompasses:
[0073] The term “tumor-associated antigen” refers to an antigen expressed in a tumor. The “tumor-associated antigen” can be selected from (but not limited to): EGFR, GPC3, HER2, EphA2, Claudin18.1, Claudin18.2, Claudin 6, GD2, EpCAM, mesothelin, CD19, CD20, ASGPR1, EGFRvIII, de4EGFR, CD19, CD33, IL13R, LMP1, PLAC 1, NY-ESO-1, MAGE4, MUC1, MUC16, LeY, CEA, CAIX (carbonic anhydrase IX), CD123.
The published specification discloses that an “extracellular binding domain” encompasses:
[0065] The term “extracellular binding domain” comprises an antibody or a ligand that specifically recognizes an antigen (such as a tumor antigen), and preferably the antibody is a single chain antibody or a single domain antibody. More preferably, the extracellular antigen-binding region of the chimeric antigen receptor is connected to the transmembrane domain of CD8 or CD28 through the hinge region of CD8, and the transmembrane domain is followed by the intracellular signal domain. In this solution, the extracellular binding domain comprises 1 or 2 antibodies, preferably, an antibody targeting FAP and/or an antibody targeting another tumor-associated antigen, and the two antibodies can be connected through a connecting peptide.
The published specification discloses that Claudin 18.2 encompasses:
[0078] The term “claudin 18.2” or “claudin 18A2” (CLD18.2, CLD18A2, CLDN18A2, or CLDN18.2) herein may also refer to a homologue, ortholog, interspecies homologue, codon-optimized form, truncated form, fragmented form, mutated form or any other known derived form (e.g., a post-translationally modified variant) of the known claudin 18A2 sequence. In some embodiments, the claudin 18A2 is a peptide having GenBank accession number NP_001002026 (mRNA: NM 001002026), having the sequence represented by SEQ ID NO: 23.
The published specification discloses that “FAP” encompasses:
[0080] The term “FAP” is also called fibroblast activation protein, which belongs to the class of serine proteases, and is a dimer consisting of two subunits, i.e., FAPα (a molecular weight of 95 kDa) and FAPβ (a molecular weight of 105 kDa), with a molecular weight of 170 kDa. FAP can be selectively expressed on more than 90% of activated fibroblasts in lung, breast and colorectal cancer stroma. FAPα has the sequence represented by SEQ ID NO: 24.
The published specification discloses proteins specifically recognizing CLDN18.2 or FAP encompass:
[0089] In a particular embodiment, the protein specifically recognizing FAP comprises an antibody targeting FAP or a ligand of FAP, and the antibody targeting FAP is a full-length antibody or an antibody fragment. The antibody fragment refers to an antibody that comprises binding ability of a full-length antibody but only has a partial structure of a full-length antibody. Examples of an antibody fragment include but are not limited to: Fv, Fab, Fab′, Fab′-SH, F(ab′)2, single chain antibody (scFv), single domain antibody, bispecific antibody, and multi-specific antibody formed from antibody fragments.
[0090] In a particular embodiment, the protein specifically recognizing claudin18.2 comprises an antibody targeting FAP or a ligand of FAP, and the antibody targeting claudin18.2 is a full-length antibody or an antibody fragment thereof. The antibody fragment refers to an antibody that comprises binding ability of a full-length antibody but only has a partial structure of the full-length antibody. Examples of the antibody fragment include but are not limited to: Fv, Fab, Fab′, Fab′-SH, F(ab′)2, single chain antibody (scFv), single domain antibody, bispecific antibody, and multi-specific antibody formed from antibody fragments.
Thus, according to the instant specification, the claims broadly encompass any proteins that recognize any species of FAP antigen, and recognize a vast genus of tumor antigens or CLDN18.2 antigens, or any ligands thereof.
The instant specification discloses an exemplary anti-FAP scFv SEQ ID NO:2 comprising VL and VH CDR SEQ ID NOs:35-40; exemplary anti-CLDN18.2 scFv SEQ ID NO:4 comprising VL and VH CDR SEQ ID NOs:26-31; exemplary single CARs comprising either anti-FAP scFv SEQ ID NOs:2 or anti-CLDN18.2 scFv SEQ ID NO:4 (Example 2); exemplary fusion FAP-CLDN18.2 CAR SEQ ID NOs:22 and 42; and exemplary fusion CLDN18.2-FAP CAR SEQ ID NOs:20 and 41, wherein the fusion CARs comprise the scFvs of SEQ ID NOs:2 and 4 ([91-92]; Example 1). The specification discloses that the fusion CARs treated xenograft tumors (Example 3).
Thus, the instant specification describes: (1) a single species of FAP antibody sequence that binds to FAP that is scFv SEQ ID NO:2 comprising the six critical CDR SEQ ID NOs: 35-40 for FAP binding and recognition; and (2) a single species of CLDN18.2 antibody sequence that binds to CLDN18.2 that is scFv SEQ ID NO:4 comprising the six critical CDR SEQ ID NOs: 26-31 for CLDN18.2 binding and recognition. The instant specification demonstrates that immune cells expressing CARs comprising these sequences function to treat cancer. The specification fails to disclose any other structural sequence required of a protein or antibody to possess the function of recognizing or binding FAP, a FAP ligand, a tumor-associated antigen, a tumor ligand, or CLDN18.2, and treating cancer as broadly claimed.
To provide adequate written description and evidence of possession of the claimed protein genus encompassed by the immune effector cells, the instant specification can structurally describe representative proteins/ligands/antibodies that function to bind FAP, a FAP ligand, a tumor-associated antigen, a tumor ligand, and CLDN18.2, or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.). A disclosure that does not adequately describe a product itself logically cannot adequately describe a method of using that product.
Although Applicants may argue that it is possible to screen for proteins/ligands/antibodies that bind FAP, ligands, tumor-associated antigens or CLDN18.2 and function as claimed, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘requires a precise definition, such as by structure, formula, chemical name, or physical properties,’ not a mere wish or plan for obtaining the claimed chemical invention.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future proteins/ligands/antibodies yet to be discovered that may function as claimed. The FAP antigen, tumor antigen, or CLDN18.2 antigens provide no information about the structure of a protein, ligand, or antibody that binds to them.
Other than for the disclosed anti-FAP and anti-CLDN18.2 CDR or scFv SEQ ID NOs, the instant specification fails to describe structural features common to the members of the genus, which features constitute a substantial portion of the genus because the instant specification fails to disclose any other representative protein sequences that function as claimed. A definition by function does not suffice to define the genus because it is only an indication of what the protein or antibody does, rather than what it is. The instant specification fails to describe a representative number of protein and antibody sequences for the genus of proteins/ligands/antibodies that function as claimed. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus required to perform the claimed method.
Additionally, with regard to the proteins being single domain antibodies, as required in claim 6, the specification does not disclose a single exemplary single domain antibody that functions as claimed. The instant specification discloses only an anti-FAP and an anti-CLDN18.2 antibody comprising all six defined VL and VH CDR SEQ ID NOs critical to the claimed binding/recognizing function. The specification does not disclose the sequence structure of any single domain antibody that would comprise less than these six CDR sequences and predictably function as claimed.
Given the lack of representative examples to support the full scope of the claimed proteins used to make the claimed immune effector cell and practice the claimed method, and given the lack of reasonable structure-function correlation with regards to the unknown sequences in the proteins/ligand/antibodies that provide FAP, tumor-associated antigen, ligand, or CLDN18.2 binding function, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of proteins that recognize FAP, tumor-associated antigen, ligand, or CLDN18.2 that is required to practice the claimed invention. Since the specification fails to adequately describe the product to which the claimed method uses, it also fails to adequately describe the method.
Examiner Suggestion: Amend claim 1 to recite and require, at minimum, all six CDR SEQ ID NOs from the VL and VH domains of the anti-FAP and anti-CLDN18.2 antibodies (i.e., SEQ ID NOs:35-40 and 26-31).
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.
4. Claim(s) 1-3, 12, and 34 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sakemura et al (Blood, 2019, 134(Supplement_1):865).
Sakemura teaches a multifunctional immune effector T-cell simultaneously expressing first and second, separate chimeric antigen receptors (CARs), wherein a first CAR comprises a binding domain to FAP, and the second CAR comprises a binding domain to tumor associated antigen BCMA (“BCMA-FAP CART cells”), and wherein the CARs were expressed by separate vectors (see entire abstract). Sakemura demonstrates successfully treating a solid tumor in a subject suffering from a tumor by administering the BCMA-FAP CART cells, particularly in a tumor microenvironment rich in cancer associated fibroblasts (CAFs) (see Figure F).
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.
5. Claim(s) 1, 12, 15, and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Sakemura et al (Blood, 2019, 134(Supplement_1):865); in view of WO2020/047306, XIAO et al, filed August 2019.
Sakemura teaches a multifunctional immune effector T-cell simultaneously expressing first and second, separate chimeric antigen receptors (CARs), wherein a first CAR comprises a binding domain to FAP, and the second CAR comprises a binding domain to tumor associated antigen BCMA (“BCMA-FAP CART cells”), and wherein the CARs were expressed by separate vectors, as set forth above.
Sakemura does not specify the FAP and BCMA binding domains on the CARs are antibodies, or disclose the typical structure of a CAR comprising a transmembrane (TM) domain, and intracellular signal domain. Sakemura teaches administering the CAR T cells pharmaceutically to treat tumors but does not specify the pharmaceutically acceptable carrier present in the method of treating tumors.
XIAO teaches the construction of FAP or BCMA CARs for expression in T cells, wherein the binding domains are an antibody, and the CARs comprise a TM and intracellular signal domain. XAIO teaches the antigen binding domains are located on separate CARs. XIAO teaches administering the CAR T cells for the treatment of tumors (Table 1; [112]; p. 54-61; Figure 1). XIAO demonstrates successful construction of CARs using antibody binding domains and expressing them in T cells (p. 71-80). XIAO teaches the CARs are administered to treat cancer in pharmaceutical compositions comprising acceptable carriers (p. 52, 56).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to utilize antibody binding domains to FAP and BCMA in the CARs of Sakemura and to include TM and intracellular signal domains. One would have been motivated to in order to provide domains on the CARs that bind to the FPA and BCAM antigens as taught by both references, and because XIAO teaches using antibodies as the binding domains and to include the TM and intracellular signaling domains as a core structure of CARs. One of ordinary skill in the art would have a reasonable expectation of success using antibodies as the binding domains in the CARs of Sakemura and including TM and intracellular signal domains because XIAO teaches known and successful methods of constructing CARs utilizing antibody binding domains, TM, and intracellular signal domains.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to include a pharmaceutically acceptable carrier in the CAR T cell composition of Sakemura administered to subject with tumors. One would have been motivated to, and have a reasonable expectation of success to, because XIAO teaches CAR T cell compositions for the treatment of cancer comprise pharmaceutically acceptable carriers.
6. Claim(s) 4, 6, 8-10, 19, 21, 23, 25-27, 29, 32, 34 are rejected under 35 U.S.C. 103 as being unpatentable over Sakemura et al (Blood, 2019, 134(Supplement_1):865); in view of WO2020/047306, XIAO et al, filed August 2019 as applied to claims 1, 12, 15, and 32 above, and further in view of US Patent Application Publication 2021/0087295, Albelda et al, claiming priority to September 2019; and Zah et al (Nature Communications, May 8, 2020; 11, article 2283).
Sakemura and XIAO (the combined references) teach CAR T cells expressing dual CARs binding to FAP or BCMA, as set forth above. XIAO further suggests the two antigen binding domains can be located on the same CAR molecule (p. 61 and [134]). XIAO teaches the construction of CARs comprising two scFv, each binding to different antigens and connected by a linker on the same CAR (see Figure 26 below; [134]). XIAO teaches constructing CARs with a TM domain and intracellular signal domain comprising CD3 zeta (CD3ζ), CD28, or 4-1BB (CD137) ([135-136]). Sakemura further teaches and demonstrates successfully treating multiple myeloma xenografts in vivo by administering dual CAR T cells simultaneously expressing FAP CAR comprising 4-1BB (CD137) intracellular signal domain BCMA CAR (BCMA-FAP) or with dual CAR T cells simultaneously expressing FAP CAR comprising 4-1BB (CD137) intracellular signal domain with CS1 CAR comprising a CD28 intracellular signal domain (BCMA-CS1), wherein treatment with dual CAR T cells resulted in a long term durable response and improved overall survival compared to single FAP CAR T cell treatment (Figure F).
XIAO Figure 26:
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The combined references do not teach a bispecific CAR fusion that comprises specifically the FAP antibody domain and BCMA antibody binding domain on the same CAR, wherein each antibody is an scFv connected by a peptide linker, the CAR further comprising the TM domain with intracellular signal domain selected from CD3 zeta (CD3ζ), CD28, or 4-1BB (CD137), nucleic acids encoding the bispecific (fusion) CAR, and treating cancer comprising administering a pharmaceutical composition comprising the bispecific CAR T cell.
Albelda teaches FAP CARs can be bispecific, where the CAR comprises binding domains to two different antigens that are arranged in tandem and separated by linker peptides ([142]). Albelda further teaches known sequences of FAP antibodies for CAR construction, and routine construction of FAP CARs comprising TM and intracellular signaling domain from CD28, 4-1BB (CD137), CD3ζ, FcR gamma; wherein the FAP antibody is an scFv (claims 1-6; [7-13]; [119-179]; Table 1; Example 4); nucleic acid encoding the CAR (claims 7-18; [14-18]; [180-213]); immune cells, T cells, NK cells, or autologous cells expressing the CAR (claims 14-17; [19-23]; [214-247]; [326-358]); pharmaceutical composition comprising the CAR-expressing immune cell and pharmaceutically acceptable carrier (claim 18; [24]; [359-368]); and methods of treating cancer in a subject comprising administering to the subject the CAR-expressing immune cell (claims 18-27; [25-31]; [119-120]; [248-311]). Albelda teaches FAP is expressed selectively by tumor associated fibroblasts (TAFs) and pericytes in more than 90 % of human epithelial cancers examined, and teaches targeting FAP with their CAR for the treatment of cancer ([5]; [25-31]; [119-120]). Albelda demonstrates their CAR T cells comprising an anti-FAP scFv, TM, and intracellular 4-1BB and CD3 signal domain (Example 4) successfully treated FAP-expressing lung cancer xenografts (Example 7; Figure 11).
Zah teaches the known, successful construction of bispecific (fusion or “OR-gate”) CARs to produce bispecific CAR T-cells for treating multiple myeloma, wherein each of the antigen binding domains of the CAR are produced from scFv connected by a peptide linker and the bispecific CAR comprises a TM domain with intracellular signal domain comprising 4-1BB (CD137) and CD3ζ (see Figure 1b below; Methods; Figure 3a). Zah produced bispecific CAR T cells targeting BCMA and CS1 tumor antigens, as well as single CAR T cells targeting only BCMA or only CS1, and treated multiple myeloma xenografts with the CAR T cells (Figure 4). Zah demonstrated that the bispecific CAR T cells resulted in improved survival over the single CAR T cells (Figure 4b). Zah teaches that producing bispecific (“OR-gate”) CAR T cells is more efficient than producing “DualCAR” construct T cells (Figure 3a), wherein DualCAR T cells have to be transduced with two genetic payloads encoding separate CARS, as opposed to one construct for bispecific CAR T cells (p. 10, col. 2). Zah teaches the prior art has already demonstrated “OR-gate” bispecific CAR T cells are more effective than single CAR T cells and DualCAR T cells both in vitro and in vivo (p. 10, col. 2). Zah teaches the bispecific CAR prevents antigen escape in CAR T cell therapy (abstract).
Zah Figure 1b:
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It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to produce a bispecific (fusion) CAR from a nucleic acid encoding a FAP scFV - BCMA scFv-TM - 4-1BB- CD3ζ construct and to treat cancer by administering a bispecific CAR T cell expressing the bispecific CAR. One would have been motivated to, and have a reasonable expectation of success to, because: (1) Sakemura demonstrates successful superior treatment of cancer with DualCAR T cells simultaneously expressing a FAP-CAR and BCMA-CAR or simultaneously expressing BCMA-CAR and CS1-CAR over single CAR T cells; (2) XIAO, Albelda, and Zah suggest, teach, and/or exemplify the known, successful construction of bispecific (fusion) CARs, where Albelda suggests making bispecific FAP CAR T cells for treatment of cancer; (3) XIAO and Albelda teach known FAP scFv sequences for the successful construction of CARs, wherein Albelda demonstrates the FAP-CAR T cells successfully treat cancer; and (4) Zah teaches and demonstrates several advantages of combining the antigen binding domains into a single fusion bispecific CAR including: demonstrating that the bispecific CAR T cells resulted in improved survival over the single CAR T cells; producing bispecific (“OR-gate”) CAR T cells is more efficient than producing “DualCAR” construct T cells; the prior art has already demonstrated “OR-gate” bispecific CAR T cells are more effective than single CAR T cells and DualCAR T cells both in vitro and in vivo; and bispecific CARs prevent antigen escape in CAR T cell therapy.
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.
7. Claims 1-4, 6, 8-10, 12, 15, 19, 21, 23, 25-27, 29, 32, and 34 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 57-76 of copending Application No. 18/575,545 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the copending application claims a bispecific CAR construct binding to both FAP and CLDN18.2, wherein the CAR comprises FAP scFv SEQ ID NO:106 that is 100% identical to instant SEQ ID NO:2 (see sequence alignment below); an engineered immune cell including T cell expressing the CAR construct encoded by a single nucleic acid expression cassette; wherein the CAR comprises a TM domain and intracellular signal domain; and a method of treating a tumor using the engineered immune cell; all of which render obvious the instantly claimed engineered immune effector cell expressing a FAP-CLDN18.2 CAR, nucleic acid encoding the CAR, and method of treating a tumor using the engineered immune cell.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Instant SEQ ID NO:2 aligned with SEQ ID NO:106
RESULT 7
US-18-575-545A-106
Sequence 106, US/18575545A
Publication No. US20250269028A1
GENERAL INFORMATION
APPLICANT: CARSGEN THERAPEUTICS CO., LTD.
TITLE OF INVENTION: CHIMERIC POLYPEPTIDE FOR REGULATING CELL PHYSIOLOGICAL ACTIVITY
FILE REFERENCE: FF00617US
CURRENT APPLICATION NUMBER: US/18/575,545A
CURRENT FILING DATE: 2023-12-29
PRIOR APPLICATION NUMBER: CN202110730083.X
PRIOR FILING DATE: 2021-06-29
PRIOR APPLICATION NUMBER: CN202111056553.5
PRIOR FILING DATE: 2021-09-09
PRIOR APPLICATION NUMBER: CN202210111505.X
PRIOR FILING DATE: 2022-01-29
NUMBER OF SEQ ID NOS: 110
SEQ ID NO 106
LENGTH: 547
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Description of artificial sequence: artificially synthesized
sequence
Query Match 100.0%; Score 1282; Length 547;
Best Local Similarity 100.0%;
Matches 244; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGSSVKVSCKASGGTFSSYAISWVRQAPGQGLEWMGGIIPIFGTANY 60
Qy 61 AQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCARDAADRDYWGQGTTVTVSSGGGG120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AQKFQGRVTITADKSTSTAYMELSSLRSEDTAVYYCARDAADRDYWGQGTTVTVSSGGGG120
Qy 121 SGGGGSGGGGSDIVMTQSPLSLPVTPGEPASISCRSSQSLLHPNGFNHLYWYLQKPGQSP180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SGGGGSGGGGSDIVMTQSPLSLPVTPGEPASISCRSSQSLLHPNGFNHLYWYLQKPGQSP180
Qy 181 QLLIYVGGNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCQQRNNKNRTFGQGTKV240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 QLLIYVGGNRASGVPDRFSGSGSGTDFTLKISRVEAEDVGVYYCQQRNNKNRTFGQGTKV240
Qy 241 EIKR 244
||||
Db 241 EIKR 244
8. Conclusion: No claim is allowed.
9. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA B GODDARD whose telephone number is (571)272-8788. The examiner can normally be reached Mon-Fri, 7am-3:30pm.
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/Laura B Goddard/Primary Examiner, Art Unit 1642