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 .
DETAILED ACTION
Status of the Claims
1. Claims 1-60 are the original claims filed 2/3/2023. In the Preliminary Amendment of 9/1/2023, claims 1-60 are canceled and new claims 61-93 are added. Claims 61-93 are all the claims. In the Response of 12/8/2025, claims 61, 64, 65-67, 69-73, 75, 77, 79-83, 85, 86, and 88-93 are amended.
Claims 61-93 are pending.
The Office Action contains new grounds for objection. The Office Action is final.
Priority
2. USAN 18/019,728, filed 02/03/2023, is a National Stage entry of PCT/US2021/ 044801, International Filing Date: 08/05/2021, PCT/US2021/044801 Claims Priority from Provisional Application 63/061,895, filed 08/06/2020, PCT/US2021/044801 Claims Priority from Provisional Application 63/074,582, filed 09/04/2020, PCT/US2021/ 044801 Claims Priority from Provisional Application 63/144,657, filed 02/02/2021.
Information Disclosure Statement
3. As of 2/12/2026, a total of two (2) IDS are filed: 9/1/2023; and 12/8/2025. The corresponding initialed and dated 1449 form is considered of record.
Withdrawal of Objections
Drawings
4. The objections to the drawing sheet(s) for Figures 5-6 and 29 for improper use of the term: “Expi293” (Figs. 5-6); and “CellTiter-Glo” (Fig. 29), which is a trade name or a mark used in commerce, is withdrawn. Replacement amended figures are considered and entered.
Specification
5. The objections to the disclosure because of informalities are withdrawn. Both clean and marked-up copies of the specification are filed.
a) The amended specification rectifies the improper use of the term, i.e., Expi293, CellTiter-Glo, ATCC, GenBank, UniProt, Sepharose, Tris, FACSCalibur, Epifectamine, OPtiMEM, Tykerb, EMBL, Quil-A, which is a trade name or a mark used in commerce.
b) The amended specification rectifies the improper citation of peptide sequences that are > 4 amino acids in length as pursuant to 37 CFR 1.821-1.825. The sequence identifier (SEQ ID NO) is provided for (GGGGS)3 and (GGGGS)6, respectively.
6. The amended abstract of the disclosure rectifies the improper use of parenthetical text.
Claim Objections
7. The objections to Claims 61-93 because of informalities is withdrawn.
a) Claims 61-93 are amended in claim 61(a) to recite “…a complementarity determining region (CDR) VH-CDR1…”
b) Claims 61-93 are amended to recite “or antigen binding fragment thereof” throughout the claim set in order to comport with generic Claim 61 reciting “antigen binding fragment thereof.”
c) Claims 61 and 67 are amended to recite “Claudin 18.2 (CLDN18.2)” to comport with independent method claims 68, 79, 83 and 85 that specifically recite CLDN18.2 and depend from Claim 61.
d) Claim 67 is amended to replace the phrase “capable of specifically binding” with “specifically binds.”
e) Claim 83 is amended to replace the phrase “configured to localize to a cancer cell” with “localizes to a cancer cell”.
g) Claim 90 is amended to correct the typographical error in order to distinguish the two antigens “CD3 and GPA33” to which the bispecific antibody binds.
h) Claim 90 is amended to delete the phrase “(melanoma antigen)”.
i) Claims 91 and 93 are amended to replace the phrase “that is armed ex vivo with” with “comprising” in Claim 91.
Withdrawal of Rejections
Claim Rejections - 35 USC § 112(b)
8. The rejection of Claims 67, 80, 82 and 89-93 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn.
a) Claim 67 is amended to include the sequence identifier (SEQ ID NO) for (GGGGS)3 and (GGGGS)6, respectively.
b) Claims 80 and 89 are amended to recite the broad recitation “lung cancer” and to delete the narrower phrase “non-small cell lung cancer (NSCLC)”.
c) Claim 82 is amended to recite the broad recitation “alkylating agents”, and to delete the narrowing statement “platinum agents”.
d) Claim 82 is amended to depend from claim 81 to provide antecedent support for the limitation "wherein the additional therapeutic agent".
e) Claims 90-93 are amended in Claim 90 to replace the phrase “(with peptides derived from TP53, KRAS, MYC, EBNA1-6, PRAME, MART, tyronsinase, MAGEAi-A6, pmel17, LMP2, or WT1)” with “with peptides derived from TP53, KRAS, MYC, EBNA1-6, PRAME, MART, tyronsinase, MAGEAi-A6, pmel17, LMP2, or WT1.”
Claim Rejections - 35 USC § 112(a)
Written Description
9. The rejection of Claims 79-82, 84, 88-89, and 93 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 is withdrawn. Method claims 79, 88, and 93 are amended to recite "a therapeutically effective amount" of the antibody or antigen binding fragment thereof, the engineered immune cell, or the T cell. As described in the instant application,
a "therapeutically effective amount" of a composition refers to composition
levels in which the physiological effects of a disease or condition are ameliorated or
eliminated.
Objections Maintained
Claim Objections
10. The objection to claim 90 is maintained because of informalities.
Applicants response that the person of ordinary skill in the art would be familiar with the common names used for such antigens, which ordinarily include both full names (e.g., "beta-catenin") as well as commonly-used abbreviations (e.g., "HER2") would be well known to the skilled artisan, is not persuasive.
Response to Arguments
Applicants comments that the use of an abbreviation with a full name are interchangeable and well understood, are not relevant to the objection. Applicants comments substantiate the duplicity of using a well-known full name with the corresponding well-known abbreviation in the same claim. Accordingly, it is not clear why different formats are used in the same claim. It is not clear why redundancy is required for some species but not others.
Applicants made a bona fide attempt at amending Claim 90 to render the citation of antigen species consistent for definition by abbreviation alone and others defined by a full name and abbreviated name. However, Applicants have not addressed why the species carcinoembryonic antigen (CEA), Pmel 17 (gp100), lung resistance protein (LRP), insulin-like growth factor (ILGF) are exempt from amendment. Note other examples that have not been addressed: cancer antigen 125 (CA-125); Epstein-Barr Virus nuclear antigen (EBNA); prostate specific antigen (PSA); colon-specific antigen-p (CSAp).
The objection is maintained.
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.
11. The provisional rejection of Claims 74 and 90-93 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 8-10, 19-23, 25-27, 31-32, 35 of copending Application No. 18/294,755 (reference application) is maintained.
Applicants request that the provisional nonstatutory double patenting rejection be held in abeyance until the rejection outstanding in the instant application are overcome is granted.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
New Grounds for Objection
Claim Objections
11. Claims 61-63, 65-73, 75-78, 83, 86-89, and 91-93 are objected to because of the following informalities:
a) Claims 61-63, 65-67, 75-78, 83, and 86-89 are not identified by the antigen to which the antibody binds.
The title of the invention is “Anti-Claudin 18.2 multi-specific antibodies and uses thereof.”
The abstract states:
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The specification does not support cross-reactivity for different antigens for the inventive clones.
[0174] In general, expression vectors useful in recombinant DNA techniques are often in the form of plasmids. In the present disclosure, “plasmid” and “vector” can be used interchangeably as the plasmid is the most commonly used form of vector. However, the present technology is intended to include such other forms of expression vectors that are not technically plasmids, such as viral vectors (e.g., replication defective retroviruses, adenoviruses and adeno-associated viruses), which serve equivalent functions. Such viral vectors permit infection of a subject and expression of a construct in that subject. In some embodiments, the expression control sequences are eukaryotic promoter systems in vectors capable of transforming or transfecting eukaryotic host cells. Once the vector has been incorporated into the appropriate host, the host is maintained under conditions suitable for high level expression of the nucleotide sequences encoding the anti-CLDN18.2 antibody, and the collection and purification of the anti-CLDN18.2 antibody, e.g., cross-reacting anti-CLDN18.2 antibodies. See generally, U.S. 2002/0199213. These expression vectors are typically replicable in the host organisms either as episomes or as an integral part of the host chromosomal DNA. Commonly, expression vectors contain selection markers, e.g., ampicillin-resistance or hygromycin-resistance, to permit detection of those cells transformed with the desired DNA sequences. Vectors can also encode signal peptide, e.g., pectate lyase, useful to direct the secretion of extracellular antibody fragments. See U.S. Pat. No. 5,576,195.
Claim 83 is included in the objection for failing to specify that the antibody binds to CLDN18.2 but instead recites a localization with a CLDN18.2-expressing cancer cell.
b) Claims 68-73 are drawn to “a Claudin 18.2 epitope” in Claim 68 and “a Claudin 18.2 (CLDN18.2) polypeptide comprising an extracellular loop 1 (EL1) sequence, optionally wherein the extracellular loop 1 (EL1) sequence comprises the amino acid sequence of SEQ ID NO: 271 in Claim 71.
The specification teaches specific binding as follows:
[0111] As used herein, “specifically binds” refers to a molecule (e.g., an antibody or antigen binding fragment thereof) which recognizes and binds another molecule (e.g., an antigen), but that does not substantially recognize and bind other molecules. The terms “specific binding,” “specifically binds to,” or is “specific for” a particular molecule (e.g., a polypeptide, or an epitope on a polypeptide), as used herein, can be exhibited, for example, by a molecule having a K.sub.D for the molecule to which it binds to of about 10.sup.−4 M, 10.sup.−5M, 10.sup.−6M, 10.sup.−7M, 10.sup.−8 M, 10.sup.−9M, 10.sup.−10 M, M or 10.sup.−12M. The term “specifically binds” may also refer to binding where a molecule (e.g., an antibody or antigen binding fragment thereof) binds to a particular polypeptide (e.g., a CLDN18.2 polypeptide), or an epitope on a particular polypeptide, without substantially binding to any other polypeptide, or polypeptide epitope.
The claims could b amended for consistency with respect to the organization of an epitope with respect to a polypeptide comprising an epitope.
c) Claims 91-93 are objected to for depending from objected claim 90.
Appropriate correction is required.
Conclusion
12. Claims 79-82 and 84-85 are allowed.
13. 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.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
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LYNN ANNE BRISTOL
Primary Examiner
Art Unit 1643
/LYNN A BRISTOL/Primary Examiner, Art Unit 1643