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. The Amendment filed April 30, 2026 in response to the Office Action of December 31, 2025, is acknowledged and has been entered. Claims 1-4, 6, 8-10, 12, 19, 21, 29, 34, 36-42 are now pending and being examined. Claims 5, 7, 11, 13-18, 20, 22-28, 30-33, 35 are canceled. Claims 1-4, 6, 8-10, 12, 19, 21, 29, and 34 are amended. Claims 36-42 are new.
New Rejection
(necessitated by amendments)
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 38 and 42 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.
Claim 38 recites “The immune effector cell according to claim 1, wherein the single chain antibody is selected from the group consisting of:…”. There are two different single chain antibodies recited in claim 1, so it is unclear which one claim 38 is referring to.
Claim 42 lists options (a)-(e) with conjunction word “or” between (a), (b), and (c), and conjunction word “and” between options (d) and (e). It is unclear based on the conjunction words what is required to be present and what is optional in the claimed pharmaceutical composition.
Maintained Rejection
(addressing amendments)
Claim Rejections - 35 USC § 112
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, 19, 21, 29, 34, and 36-42 remain/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 now drawn to a multifunctional immune effector cell expressing a protein that is a single chain antibody targeting FAP and protein that is a single chain antibody targeting Claudin 18.2. Dependent claims recite the proteins are expressed as a fusion protein. The claims recite the single chain antibodies or fusion protein expressed by the multifunctional immune effector cell function to:
Specifically recognize FAP and Claudin 18.2;
target FAP and target Claudin 18.2; and
treat a tumor.
No sequence structure is recited for the single chain antibodies specifically recognizing FAP and Claudin18.2 that also treat a tumor.
Dependent claim 38 recites a partial protein structure, requiring only one of the recited light chain and heavy chain CDR sequences of either the single chain antibody targeting FAP or the single chain antibody targeting Claudin 18.2, but not both, wherein the single chain antibody targeting FAP comprises CDR SEQ ID NOs:35-40 or anti-FAP scFv SEQ ID NO:2; and wherein the single chain antibody targeting CLDN18.2 comprises 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 single chain antibodies recognizing and targeting FAP and Claudin 18.2 required to function as listed above.
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.
Thus, according to the instant specification, the claims broadly encompass any single chain antibodies that recognize any species of FAP antigen, and recognize a vast genus of CLDN18.2 antigens.
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 an scFv to possess the function of recognizing or binding FAP or CLDN18.2, and treating cancer as broadly claimed.
To provide adequate written description and evidence of possession of the claimed single chain antibody (scFv) genus encompassed by the immune effector cells, fusion protein, and nucleic acids, the instant specification can structurally describe representative single chain antibodies that function to bind FAP and bind 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 single chain antibodies that bind FAP 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 and CLDN18.2 antigens provide no information about the structure of an 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 scFv 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 antibody does, rather than what it is. The instant specification fails to describe a representative number of antibody sequences for the genus of scFv 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.
Given the lack of representative examples to support the full scope of the claimed single chain antibodies used to make the claimed immune effector cell, fusion protein, nucleic acid, and to practice the claimed method, and given the lack of reasonable structure-function correlation with regards to the unknown sequences in the antibodies that provide FAP and CLDN18.2 binding function, the present claims lack adequate written description. Thus, the specification does not provide an adequate written description of single chain antibodies that recognize FAP and 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).
Response to Arguments
4. Applicants point to MPEP 2163 (II)(2) and argue that written description should consider the level of skill and knowledge in the art. Applicants argue that the instant specification adequately describes immune effector cells expressing proteins that comprise scFvs against FAP and Claudin 18.2. Applicants argue that the target antigens FAP and Claudin 18.2 are well-characterized antigens in the art, and the claims explicitly requires an scFv antibody format that is a well-characterized antigen-binding scaffold. Applicants argue that the written description requirement is met without requiring CDR sequences for the scFvs. Applicant argue the specification discloses xemplary species of scFv targeting FAP and Claudin 18.2. Applicants argue that one of ordinary skill in the art could predictably obtain, by conventional methods, candidate antibodies having an scFv that recognizes FAP and Claudin 18.2. Applicants argue that a person skilled in the art would have no substantial technical obstacle nor would undue experimentation be required to produce scFvs that recognize FAP and Claudin 18.2.
5. The arguments have been carefully considered but are not persuasive. Examiner maintains the standards for written description according to the decisions in Lily and Enzo have not been met. As stated in the rejection, the genus of claimed scFvs recognizing FAP and Claudin 18.2 is vast, regardless of whether they are binding a single species of human FAP and Claudin 18.2 antigen, or whether they are binding to a genus of FAP and Claudin 18.2 proteins and variants as encompassed by the claims. No claims recite and require, at minimum, the six CDR SEQ ID NOs from the heavy and light chains of the anti-Fap and anti-Claudin 18.2 scFvs critical to performing the claimed function of recognizing and targeting FAP and Claudin 18.2., that would allow one to recognize members of the claimed genus required to make and practice the claimed inventions.
With regards to exemplary species for the claimed vast genus of scFvs, 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 specification fails to disclose any other exemplary species of structural sequence required of an scFv to possess the function of recognizing or binding FAP or CLDN18.2, and treating cancer that would allow one to recognize members of the claimed genus required to make and practice the claimed inventions.
Although Applicants argue that methods of making scFvs that bind to known antigens is routine and well established, Examiner maintains that knowledge of routine methods of making scFvs that bind to FAP or Claudin 18.2 antigens fails to put Applicants in possession of the vast genus of scFvs, fusion proteins comprising them, nucleic acids encoding them, immune cells expressing them, and methods employing them as claimed. Methods of producing scFvs that bind to antigens provides no information on the structure of the resulting scFvs that would allow one to immediately recognize members of the vast genus that bind to FAP and Claudin 18.2 and function as claimed. Further, the generic scFv antibody format or scaffold provides no information on the CDR sequence structure critical to performing the claimed functions of recognizing and targeting FAP and Claudin 18.2. As stated in the rejection, 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 antibodies or scFvs yet to be discovered that may function as claimed. The FAP and CLDN18.2 antigens provide no information about the structure of an antibody or scFv that binds to them.
MPEP 2163 (II) (3)(a) states:
Conversely, describing a composition by its function alone typically will not suffice to sufficiently describe the composition. See Eli Lilly, 119 F.3 at 1568, 43 USPQ2d at 1406 (Holding that description of a gene’s function will not enable claims to the gene "because it is only an indication of what the gene does, rather than what it is."); see also Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen Inc. v. Chugai Pharm. Co., 927 F.2d 1200, 18 USPQ2d 1016 (Fed. Cir. 1991)). An adequate written description of a chemical invention also requires a precise definition, such as by structure, formula, chemical name, or physical properties, and not merely a wish or plan for obtaining the chemical invention claimed. See, e.g., Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 927, 69 USPQ2d 1886, 1894-95 (Fed. Cir. 2004) (The patent at issue claimed a method of selectively inhibiting PGHS-2 activity by administering a non-steroidal compound that selectively inhibits activity of the PGHS-2 gene product, however the patent did not disclose any compounds that can be used in the claimed methods. While there was a description of assays for screening compounds to identify those that inhibit the expression or activity of the PGHS-2 gene product, there was no disclosure of which peptides, polynucleotides, and small organic molecules selectively inhibit PGHS-2. The court held that "[w]ithout such disclosure, the claimed methods cannot be said to have been described.").
For example, disclosure of an antigen fully characterized by its structure, formula, chemical name, physical properties, or deposit in a public depository does not, without more, provide an adequate written description of an antibody claimed by its binding affinity to that antigen, even when preparation of such an antibody is routine and conventional. See Amgen Inc. v. Sanofi, 872 F.3d 1367, 1378, 124 USPQ2d 1354, 1361 (Fed. Cir. 2017)("knowledge of the chemical structure of an antigen [does not give] the required kind of structure-identifying information about the corresponding antibodies")
In the instant case, the scFvs recognizing FAP and Claudin 18.2 are critical to making and practicing the claimed inventions. Other than the single species of FAP and Claudin 18.2 monoclonal antibody CDR and scFv sequences disclosed, the instant specification does not disclose which of the universe of scFvs will predictably recognize and target the genus of FAP and Claudin 18.2 antigens, as broadly encompassed by the claims. The recitation of “targeting FAP” and “targeting Claudin 18.2” in the claims is only an indication of what the scFv do, rather than what they are. Disclosure of the FAP and Claudin 18.2 antigens does not, without more, provide an adequate written description of an antibody claimed by its binding affinity to that antigen, even when preparation of such an antibody is routine and conventional. Therefore, the instant specification fails to provide adequate written description for the vast genus of scFvs required to make and practice the claimed inventions.
Maintained Rejection
(addressing amendments with additional Xiao reference)
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.
6. Claims 1-4, 6, 8-10, 12, 19, 21, 29, 34, 36-42 remain/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) in view of WO2020/047306, Xiao et al, filed August 2019. 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 and Claudin 18.2 scFv SEQ ID NO:108 that is 100% identical to instant SEQ ID NO:4 (see sequence alignments 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.
The copending application does not claim the chimeric receptor comprises in order: scFv - linker - scFv -TMD of CD28 - intracellular costimulatory domain 4-1BB (CD137) – intracellular stimulatory domain CD3ζ (claim 39).
The copending application does not claim a virus comprises a nucleic acid encoding the fusion protein (claim 41).
The copending application does not claim a pharmaceutical composition comprising the immune effector cell, fusion protein or nucleic acid encoding the fusion protein (claim 42).
Xiao teaches the construction of immune cells, such as T cells, expressing chimeric antigen receptors (CARs), wherein the cells can express separate CARS comprising an antigen binding domain that is an scFv, or wherein the CARs are a bispecific scFv fusion and comprising scFv binding domains that bind to different antigens, and suggests the CAR binds to tumor antigens such as FAP or Claudin 18.2, ([110-112]; [134]; [171]; Table 1; Figure 26; [175] Exemplary embodiments 184, 238, 250-252, 266-267). Xiao teaches constructing CARs with a TM domain derived from CD28, an intracellular costimulatory domain 4-1BB (CD137), and an intracellular signaling domain comprising CD3 zeta (CD3ζ) ([135-136]) and constructed in the order of scFv – linker peptide - scFv – TM domain – intracellular costimulatory domain - intracellular signaling domain CD3ζ (Figure 26; [108]; [175] Exemplary embodiments 183, 208, 223-225, 237, 261-262, 266-267). Xiao teaches nucleic acids encoding the scFv or CAR and viruses comprising the nucleic acids as expression vectors (Figure 1; [63]; [70]; [101]; [146-148]; [175] Exemplary embodiments 215-216, 240-243, 253-254, 268-269). Xiao teaches the antigen binding domains are located on the same CAR or in separate CARs ([107]; [171]; Figure 1 and 26). Xiao teaches administering the CAR T cells for the treatment of tumors (p. 54-61). 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; [175] Exemplary embodiments 193, 213, 247, 257, 271).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to construct and organize the bispecific CAR of the copending application as: anti-FAP + anti-Claudin 18.2 scFv fusion protein -TMD of CD28-intracellular domain CD3ζ and/or 4-1BB (CD137); produce a virus vector comprising a nucleic acid sequence encoding the CAR; and produce a pharmaceutical composition comprising the immune effector cells expressing the CAR. One would have been motivated to, and have a reasonable expectation of success to, given 1) the copending application claims immune effector cells expressing CARs or bispecific CARs that comprise an scFv(s) that binds to FAP and/or Claudin 18.2 for the treatment of tumors, wherein the CARs comprise a transmembrane domain and intracellular signaling domain; 2) Xiao also teaches immune effector cells expressing CARs or bispecific CARS that comprise scFvs or fusion scFvs binding to two different tumor antigens, wherein tumor antigens include FAP or Claudin 18.2, for the treatment of tumors, 3) Xiao teaches routine methods of making the immune effector cells by transducing them with viral vectors expressing nucleic acids encoding the CARs, 4) Xiao teaches routine construction of CARs with the structure of scFv binding domain - CD28 TM domain – 4-1BB costimulatory domain - CD3ζ intracellular signaling domain; and 5) Xiao teaches known formulations of pharmaceutical compositions comprising the immune effector cells expressing the CARs for treatment of cancer.
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 18/575,545 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
Instant SEQ ID NO:4 aligned with 18/575,545 SEQ ID NO:108:
RESULT 10
US-18-575-545A-108
Sequence 108, US/18575545A
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 108
LENGTH: 550
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Description of artificial sequence: artificially synthesized
sequence
Query Match 100.0%; Score 1318; Length 550;
Best Local Similarity 100.0%;
Matches 247; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLQESGPGLIKPSQTLSLTCTVSGGSISSGYNWHWIRQPPGKGLEWIGYIHYTGSTNY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLQESGPGLIKPSQTLSLTCTVSGGSISSGYNWHWIRQPPGKGLEWIGYIHYTGSTNY 60
Qy 61 NPALRSRVTISVDTSKNQFSLKLSSVTAADTAIYYCARIYNGNSFPYWGQGTTVTVSSGG 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NPALRSRVTISVDTSKNQFSLKLSSVTAADTAIYYCARIYNGNSFPYWGQGTTVTVSSGG 120
Qy 121 GGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLFNSGNQKNYLTWYQQKPG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GGSGGGGSGGGGSDIVMTQSPDSLAVSLGERATINCKSSQSLFNSGNQKNYLTWYQQKPG 180
Qy 181 QPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQNAYSFPYTFGGG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 QPPKLLIYWASTRESGVPDRFSGSGSGTDFTLTISSLQAEDVAVYYCQNAYSFPYTFGGG 240
Qy 241 TKLEIKR 247
|||||||
Db 241 TKLEIKR 247
Response to Arguments
7. Applicants argue that based on the claim amendments, the pending claims are distinct from those of the cited application.
8. The arguments have been considered but are not persuasive. The amendments were addressed in the rejection above and Examiner maintains the copending claims render obvious the instant invention.
9. All other rejections recited in the Office Action mailed December 31, 2025 are hereby withdrawn in view of amendments. The rejection of claims under 35 U.S.C. 102(a)(1) and 35 U.S.C. 103 over Sakemura et al (Blood, 2019, 134(Supplement_1):865) are withdrawn in view of claim amendments requiring a protein specifically binding to Claudin 18.2. Sakemura does not teach or suggest a CLDN 18.2 CAR or combining FAP and CLDN 18.2.
Additional prior art made of record but not relied upon is WO 2020/023679, Lin et al, claiming priority to July 2018. Lin teaches making anti-CLDN 18.2 antibodies including scFvs. Lin teaches chimeric antigen receptors (CARs) that comprise a binding domain to Claudin 18.2 (CLDN 18.2) – transmembrane domain from CD8, CD28, or CD3 - intracellular signaling domain from CD28, CD3 and/or 4-1BB (CD137) ([259-264]; [277]; [296-297]). Lin teaches T cells or NK cells are transfected with a nucleic acid encoding the CAR to produce CLDN 18.2 CAR T cells; wherein the nucleic acid sequence is comprised within a virus vector (([265-272]; [278-287]; [301-303]; claims 20-28, 36-37). Lin teaches administering the CLDN 18.2 CAR T or CAR NK cells to treat cancer expressing CLDN 18.2, including pancreatic cancer and gastrointestinal tumors ([3-4]; [116]; [128]; [246]; [304-306]; [308-310]; [314]; claims 38-48). Lin teaches pharmaceutical composition comprising the CLDN18.2 CAR or CAR T cells ([307]; [327-329]; claim 29).
Lin suggests making bispecific CLDN18. 2 antibodies to target 2nd tumor antigens such as FAP, in order to reduce off-target effects and to provide synergistic anti-tumor effects ([222]), but does not teach or suggest: 1) making a bispecific CAR binding to both CLDN 18.2 and FAP, or 2) making a CAR T cell or CAR NK cell expressing a CLDN 18.2 CAR and a FAP CAR.
Ali et al (Frontiers in Oncology, 2019, 9:56, pages 1-14) review clinical treatments for pancreatic cancer including CLDN 18.2 CAR T cells that were produced by lentiviral transduction of CLDN 18.2 CAR (Table 1; p. ) and FAP scFv CAR T cells (p. 9, col. 1). Ali does not teach or suggest the CAR T cells express both CLDN 18.2 CAR and FAP CAR, or that the CAR T cells express a bispecific CLDN 18.2-FAP CAR.
10. Conclusion: No claim is allowed.
Conclusion
11. THIS ACTION IS MADE FINAL. 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.
12. 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
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