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 .
Election/Restrictions
1. Applicant’s election without traverse of mixed population of CD4+ and CD8+ T-cells as the species of cells and a single dose as the species of administration regimen in the reply filed on 03/04/2026 is acknowledged.
Claims 2, 4-7, 9, 10, 13-14, 17-20, 23-31, 33, and 35-46 have been cancelled. Claims 1, 3, 8, 11, 12, 15, 16, 21, 22, 32, 34, and 47 have been amended. Claims 48-55 are new.
Claims 1, 3, 8, 11, 12, 15, 16, 21, 22, 32, 34, and 47-55 are under examination.
Claim Objections
2. Claim 1 is objected to because of the recitations: (1) “binds the peptide antigen of MAGE A4” (line 5); and (2) “a peptide antigen of MAGE A4 comprising” (line 20).
Correction to (1) “binds a MAGE A4 peptide”; and (2) “expresses the MAGE A4 peptide and wherein the MAGE A4 peptide comprises” is suggested.
3. Claim 3 should recite “the MAGE A4 peptide” in line 2.
4. Claim 15 should recite “the heterologous TCR” (line 2).
5. Claim 34 should recite “the heterologous TCR” (second to last line).
6. Claims 49 and 50 are objected to because of the recitation that SEQ ID NO: 6 is the amino acid sequence of the beta chain. As disclosed by the specification, SEQ ID NO: 6 is the nucleic acid encoding the alpha chain (see p. 46-47). It is clear that this is a typographical error and the intent was to recite SEQ ID NO: 7.
Correction to replace the recitation “SEQ ID NO: 6” with “SEQ ID NO: 7” is required.
For examination purposes, the claims are reasonably interpreted as reciting SEQ ID NO: 7.
Double Patenting
7. 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.
8. Claims 1, 8, 11, 15, 16, 21, 22, 32, 34, 47-50, 54, and 55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 49-61 and 63-69 of copending Application No. 17/924,982 (reference application), in view of Melchiori et al. (WO 20/109616). Although the claims at issue are not identical, they are not patentably distinct from each other because both claim sets are drawn to the same method for treating MAGE-A4-expressing cancer by using the same modified immunoresponsive cells comprising the same MAGE-A4-binding TCR. The application specification discloses that the modified immunoresponsive cells further comprise 4-1BB (see p. 5, lines 25-28; p. 6, lines 13-15). The only difference is that the application claims recite treating synovial sarcoma, while the instant claims recite treating gastroesophageal cancer. However, it was known in the prior art that that gastroesophageal cancer (such as esophagogastric junction cancer) express MSGE-A4 and T-cells genetically engineered to express TCRs binding the GVYDGREHTV MAGE-A4 peptide such as the ones recited in the application claims could be used to treat these cancers (see Melchiori et al., p. 3, lines 16-27; p. 5, lines 6-18; p. 30, line 25 through p. 32, line 8). One of skill in the art would have known that the immunoresponsive cells recited in the application claims could be used to treat MAGE-A4-expressing gastroesophageal cancer, including esophagogastric junction cancer. One of skill in the art would have reasonably regarded treating MAGE-A4-expressing esophageal cancers as an obvious variant of the application claims. Modifying the application claims by administering the recited immunoresponsive cells to subjects affected by gastroesophageal cancer would have been obvious to one of skill in the art, to achieve the predictable result of treating the cancer in the subjects.
Thus, the instant claims and the application claims are obvious variants.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Rejections - 35 USC § 112(a) – written description
9. 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.
10. Claims 11, 49, and 53 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Adequate written description requires more than a mere statement that it is part of the invention. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC1993). The Guidelines for the Examination of Patent Application Under the 35 U.S.C.112, ¶1”Written Description Requirement” makes it clear that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species disclosures of relevant, identifying characteristics, i.e., structure or other physical and or chemical properties, functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus (Federal Register, Vol. 66, No. 4, pages 1099-1111, Friday January 5, 2001, see especially page 1106 3rd column).
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail such that the Artisan can reasonably conclude the inventors had possession of the claimed invention. Such possession may be demonstrated by describing the claimed invention with all its limitations using such descriptive means as words, structures, figures, diagrams, and/or formulae that fully set forth the claimed invention. Possession may be shown by an actual reduction to practice, showing that the invention was “ready for patenting”, or by describing distinguishing identifying characteristics sufficient to show that the Applicants were in possession of the claimed invention (January 5, 2001, Fed. Reg., Vol. 66, No. 4, pp.1099-11).
In analyzing whether the written description requirement is met for the genus claims, it is determined whether representative numbers of species have been described by their complete structure and functional characteristics.
Claim 11 recites a broad genus of TCR[Symbol font/0x61] and TCR β variable domains having an amino acid sequence at least 80% identical to SEQ ID NO: 9 and 10, respectively. Claim 49 recites a broad genus of TCR[Symbol font/0x61] and TCR β chains having an amino acid sequence at least 80% identical to SEQ ID NO: 5 and 7, respectively. Claim 53 recites a broad genus of CD8[Symbol font/0x61] having an amino acid sequence at least 80% identical to SEQ ID NO: 3. Thus, the claims are broadly drawn to genera of polypeptide variants, When viewed in light of the specification, the variants belong to broad genera of polypeptides comprising deletions, insertions, or substitutions in SEQ ID NOs: 3, 5, 7, 9, and 10 (see p. 12, line 25 through p. 13, line 14; p. 16, line 30 through p. 17, line 20). These variants may or may not be active. The genera of variants are described by their function, but the specification does not provide any disclosure as to what would have been the complete structure of sufficient number of species of the claimed genera. Additionally, the specification does not describe what would have been the identifying characteristics, such as specific features and functional attributes, of the different variants. Applicant has not provided any information besides the characterization of the genus as having TCR or CD8 activity. This limited characterization, however, does not indicate that the applicant had possession of the claimed genera of variants having the desired activity, a feature deemed essential for the instant invention.
Applicant is relying upon biological activity and the disclosure of one amino
Acid sequence for each TCR[Symbol font/0x61], TCRβ, and CD8[Symbol font/0x61] to support the entire
genera. It is well known that minor structural differences among even structurally
related compounds can result in substantially different biology. For example, Seffernick
et al. (J. Bacteriol., 2001, 183: 2405-2410) teach that proteins that are 98% identical
could have distinct activities (see Abstract). Witkowski et al. (Biochemistry, 1999, 38:
11643-11650) teach that a change of a single amino acid can result in a different
function (see Abstract). One of skill in the art would know that a change of even one amino acid residue in the claimed sequence could render an inactive protein or a protein with a different activity. Perret et al. (US 2025/0114433) teach a TCRβ having 98% identity to the claimed SEQ ID NO: 7, which is specific for KRAS, not MAGE-A4 (see p. 119, sequence 465; see the attached Sequence Alignment). One of skill in the art would not know where modifications could be introduced such as to preserve activity, and thus, would not recognize the applicant to be in possession of the entire claimed genera.
In conclusion, the limited information provided by the specification is not sufficient
to reasonably convey to one of skill in the art that applicant invented what is claimed.
Claim Rejections - 35 USC § 112(b)
11. 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.
12. Claims 1, 3, 8, 11, 12, 15, 16, 21, 22, 32, 34, and 47-55 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 1 recites the limitation "the peptide antigen of MAGE A4" in line 5. However, MAGE A4 is a protein comprising many peptides (see the attached GenBank Accession No NM_001011348); thus, there is insufficient antecedent basis for the limitation “the peptide of MAGE A4” in the claim.
Claims 3, 8, 11, 12, 15, 16, 21, 22, 32, 34, and 47-55 are rejected for being dependent from the rejected claim 1 and also for failing to further clarify the basis of the rejection.
Claim Rejections - 35 USC § 102
13. 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.
14. Claims 1, 3, 8, 11, 12, 15, 16, 21, 22, 32, and 47-54 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Melchiori et al. (WO 20/109616; cited on the IDS filed on 08/15/2024).
Melchiori et al. teach a method for treating esophagogastric junction cancer in a subject by administering to the subject a mixed population of modified CD4+ and CD8+ T-cells expressing a heterologous TCR and a CD8[Symbol font/0x61][Symbol font/0x61] coreceptor; the TCR selectively bind the MAGE-A4 peptide GVYDGREHTV expressed by the cancer cells, where the peptide is complexed with an HLA. The heterologous TCR comprises: (1) [Symbol font/0x61]CDRs1-3 comprising the amino acid sequences VSPFSN, LTFSEN, CVVSGGTDSWGKLQF respectively; and (2) βCDR1-3 comprising the amino acid sequences KGHDR, SFDVKD, CATSGOGAYEEQFF, respectively. The CD8[Symbol font/0x61][Symbol font/0x61] coreceptor comprises CDRs1-3 comprising the amino acid sequences VLLSNPTSG; YLSQNKPK; and LSNSIM, respectively. The TCR[Symbol font/0x61] chain variable domain is set forth by SEQ ID NO: 3, while TCRβ chain variable domain is set forth by SEQ ID NO: 5 (claims 1, 3, 8, 12, 16, 32, 49-52, and 54) (see p. 3, lines 11-15; p. 5, lines 6-18; p. 30, line 25 through p. 32, line 8; p. 37, line 39 through p. 38, line 2; p. 40, lines 34-37). As evidenced by the attached Sequence Alignments, SEQ ID NOs: 3 and 5 are identical to the claimed SEQ ID NOs: 5 and 7, respectively.
With respect to claims 11 and 48, Melchiori et al. teach that the amino acid sequence of the TCR[Symbol font/0x61] is set forth by SEQ ID NO: 7, while that of the TCRβ is set forth by SEQ ID NO: 8 (see p. 13, lines 34-40; p. 49, line 59 through p. 50, line 3). As evidenced by the attached Sequence Alignments, SEQ ID NOs: 7 and 8 are identical to the claimed SEQ ID NOs: 9 and 10.
With respect to claim 15, Melchiori et al. teach that the modified T-cells further comprise 4-1BBL or CD80 (see p. 28, lines 4-7).
With respect to claims 21 and 22, Melchiori et al. teach administering 1x109 of modified T-cells as a single dose (see p. 28, lines 11-17).
With respect to claim 47, Melchiori et al. teach that treatment improves time to progression, overall survival, or progression free survival (see p. 26, lines 13-20).
With respect to claim 53, Melchiori et al. teach that CD8[Symbol font/0x61] comprises the amino acid sequence set forth by SEQ ID NO: 1 (see p. 8, lines 32-37). As evidenced by the attached Sequence Alignment, SEQ ID NOs: 1 is identical to the claimed SEQ ID NO: 3.
Thus, Melchiori et al. teach all claim limitations and anticipate the claimed invention.
Claim Rejections - 35 USC § 103
15. 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.
16. Claims 1, 3, 8, 11, 12, 15, 16, 21, 22, 32, 34, and 47-55 are rejected under 35 U.S.C. 103 as being unpatentable over Melchiori et al., in view of Besser et al. (J. Immunother., 2009, 32: 415-423).
The teachings of Melchiori et al. are applied as above for claims 1, 3, 8, 11, 12, 15, 16, 21, 22, 32, and 47-54. Melchiori et al. do not specifically teach lymphodepleting chemotherapy (claim 34), nor do they teach administering the modified T-cells to patients that were previously treated unsuccessfully with chemotherapy (claim 55). Besser et al. teach adoptive transfer of antitumor T-cells to treat patients that were previously treated unsuccessfully with chemotherapy; the adoptive transfer entails lymphodepleting chemotherapy starting 7 days immediately before the administration of large numbers of antitumor T-cells; lymphodepleting chemotherapy provides the optimal environment for the antitumor T-cells and enhances the therapeutic effect (column 1 and column 2, first paragraph; paragraph bridging p. 420 and 421). One of skill in the art would have found obvious to modify the method of Melchiori et al. by using lymphodepleting chemotherapy, with the reasonable expectation that doing so would enhance the therapeutic effect.
Thus, the claimed invention was prima facie obvious at the time of its effective filing date.
17. No claim is allowed. No claim is free of prior art.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ILEANA POPA whose telephone number is (571)272-5546. The examiner can normally be reached 8:00 am to 4:30 pm.
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/ILEANA POPA/Primary Examiner, Art Unit 1633
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