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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on March 31, 2026 has been entered.
DETAILED ACTION
The amendment filed March 31, 2026 in response to the Office Action of October 1, 2025 is acknowledged and has been entered.
Claims 12, 14, 15, and 18 have been cancelled.
Claims 34-40 have been added.
Claims 19-40 are pending.
Claims 19-33 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions or species, there being no allowable generic or linking claim.
Claims 34-40 are currently under consideration as drawn to the elected invention.
In view of the claim amendments and Applicant’s arguments, the 103 rejection set forth in the previous Office Action of October 1, 2025 is hereby withdrawn. In particular, the prior art does not teach or suggest any “extracellular binding domain binds to the heavy chain constant region of the antibody, but does not bind to an otherwise identical heavy chain constant region that lacks both the substitutions of (1) and the deletion of (2)”. Given the unpredictability in the art, one of ordinary skill in the art would not be able to reach the claimed “extracellular binding domain” and the method using the “extracellular binding domain”.
Similarly, in view of the claim amendments and Applicant’s arguments, the Double Patenting rejection set forth in the previous Office Action of October 1, 2025 is hereby withdrawn.
Information Disclosure Statement
The Information Disclosure Statement filed on 03/31/2026 has been considered and entered by examiner.
Claim Objections
Claim 37 is objected to because of the following informalities: “the antibody comprises” at line 1 should be “the heavy chain constant region of the antibody comprises”. Appropriate correction is required.
Claim 38 is objected to because of the following informalities: “the antibody comprises” at line 1 should be “the heavy chain constant region of the antibody comprises”. Appropriate correction is required.
Claim 39 is objected to because of the following informalities: “the antibody comprises” at line 1 should be “the heavy chain constant region of the antibody comprises”. Appropriate correction is required.
MAINTAINED REJECTION
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.
Claims 34-40 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. This is a WRITTEN DESCRIPTION rejection.
Independent claims 34 and 40 encompass a broad genus of extracellular binding domains comprising a heavy chain variable region and a light chain variable region capable of binding to antibody constant region with mutations at multiple positions, including either:(1) substitutions at EU numbering positions 235, 236, and 239, including one or more of the following substitutions: arginine at EU numbering position 235, arginine at EU numbering position 236, and lysine at EU numbering position 239; or (2) a deletion of the amino acids at EU numbering positions 446 and 447. The substitutions of option (1) encompass hundreds of different substitution combinations at positions 235, 236 and 239. Given Broadest Reasonable Interpretation (BRI), “an extracellular binding domain” would at least encompass, antibodies (e.g. scFv) to the mutated Fc domains. The specification discloses only one binding domain (antibodies) which can bind a specific silent-Fc domain with specific substitutions of 235R/236R/239K (SEQ ID NO: 3); and only one binding domain (antibodies) can bind a specific Delta GK-Fc with 446/447 double deletion (SEQ ID NO: 5) ([1345], Example 2 and Table 6). Thus, the specification fails to provide adequate written description to demonstrate that Applicant was in possession of the claimed genus.
Vas-Gath, Inc. v" Mahurkar, 19 USPQ2d 1111, makes clear that "to satisfy the written description requirement, an applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention, and that the invention, in that context, is whatever is now claimed".
Additionally, on 22 February 2018, the USPTO provided a Memorandum clarifying the Written Description Guidelines for claims drawn to antibodies, which can be found at www.uspto.gov/sites/default/files/documents/amgen_22feb2018.pdf. That Memorandum indicates that, in compliance with recent legal decisions, the disclosure of a fully characterized antigen no longer is sufficient written description of an antibody to that antigen.
Accordingly, the instant claims have been evaluated in view of that guidance. By the time the invention was made, it is well established in the art that the formation of an intact antigen-binding site in an antibody usually required the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three "complementarity determining regions" ("CDRs") which provide the majority of the contact residues for the binding of the antibody to its target epitope (Almagro & Fransson, Frontiers in Bioscience 2008; 13: 1619-33 (see Section 3) "Antibody Structure and the Antigen Binding Site" and Figure 1, of record). Even a single point mutation in HCDR1 region could lead to antibody lose its binding activity (Ni et al., The Protein Journal, 43, pp. 683-696, July 2024, see Abstract, of record). Thus, the specific antibody disclosed by the specification would not tell structure of other mutated antibodies to GPC3, or mutated antibody to other antigens.
Regarding “an extracellular binding domain of the chimeric receptor”, given BRI, “an extracellular binding domain” would at least encompass, antibodies (e.g. scFv) to the mutated Fc domains with different substitutions. The specification discloses only one binding domain (a specific antibody: SKA0009, see Example 2, [1345]) which can bind a specific silent-Fc domain (235R/236R/239K) of SEQ ID NO: 3; and only one binding domain ( a specific antibody: YG55, see Example 2, [1345]) can bind a specific Delta GK-Fc (446/447 double deletion) of SEQ ID NO: 5 ([1345], Example 2 and Table 6). The specification discloses the chimeric receptor comprising only one binding domain (derived from the specific antibody SKA0009) which can be used in the claimed method (Examples 5 and 6). The specification does not teach other extracellular binding domain which can bind to mutations encompassed by the claims, even for the elected species: 235R/236R/239K mutation combination. As set forth above, these disclosed antibodies does not teach other antibodies with different CDRs from the disclosed antibodies which can bind to the same mutated Fc, or antibodies which can bind to other mutated Fc domains. Given the well-known high level of polymorphism of immunoglobulins/antibodies, the skilled artisan would not have been in possession of the vast repertoire of extracellular binding domains encompassed by the claimed invention.
In addition, the claims identify the extracellular binding domain by function, where the function is:
binding to the heavy chain constant region of the antibody (with mutations), but not to an otherwise identical heavy chain constant region that lacks the mutations;
inducing in an immune effector function against the cancer cells.
Based on the Examples of the instant specification (Examples 5 and 6), the treatment is depending on 1) the mutated antibody which targets an antigen specific to a tumor and 2) the extracellular binding domain which specifically bind to mutated antibody Fc domain but not wildtype Fc domain.
The specification and prior art have not established the relationship between the claimed functions and the structure of the antibody. In particular, antibodies, which bind to mutated Fc domain, may also bind to wild-type Fc domain, depending on the epitope of the antibodies. In the instant case, it is not clear whether the two antibodies (SKA0009 and YG55) disclosed in the specification bind to a naturally occurring human IgG heavy chain constant region without the mutations. One of ordinary skilled in the art would not be able to readily recognize/visualize an antibody with required properties. Without knowing the relationship between the extracellular binding domain structure and the binding specificity to mutated Fc domain (even for elected substitutions: 235R/236R/239K), one of ordinary skill in the art would not be able to quickly visualize or recognize “an extracellular binding domain” which can be used in the claimed method.
Although Applicants may argue that it is possible to screen for antibodies with claimed properties/functions, 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 antibodies or antibody fragments yet to be discovered that may function as claimed.
Taken together, the instant specification has not provided a sufficient description showing the necessary functional characteristics coupled with a known or disclosed correlation between functions and the structure. Thus, the specification is not sufficient to show the applicant was in possession of the genus of extracellular binding domain broadly encompassed for the claimed method. Logically, the specification is not sufficient to show the applicant was in possession of the claimed methods.
Response to Arguments
For the 112(a) Written Description rejection, Applicant argues:
The Office action at page 5 cites a 2010 reference (Cartiellieri et al.) as saying that "so far no general a priori rules can be defined for the [functionality] of any given binding moiety in the context of a chimeric receptor. ... " The Office's reliance on a view of the state of the art described 9 years before the present application's priority date does not take into account the fact that progress had certainly been made in the field of chimeric receptors in the years since that article was published. Nor does it take into account the fact that Cartiellieri et al. was talking about prior art chimeric receptors, in which the "binding moiety" (i.e., the extracellular binding domain of the chimeric receptor) binds directly to an antigen on a target cell. The presently claimed methods use a distinctly different approach, in which the extracellular domain of the chimeric receptor binds not to an antigen on a target cell, but rather to the heavy chain constant region of an antibody. It is the antigen-binding domain of the antibody that binds directly to the target cell antigen, thereby forming a bridge between the CAR-T cell and the target cell. The Office has suggested no reason that Cartiellieri et al.' s teachings about "functionality" of the chimeric receptor's extracellular binding domain would apply when that binding domain does not bind directly to the target antigen on a cell. And applicant sees no reason that those teachings should apply. Applicant has demonstrated that the chimeric receptor described in the present claims possesses the desired "functionality" when used in the presently claimed methods.
The Office action at page 7 expressed concern that the extracellular binding domain of the chimeric receptor might encompass structures that are not antibodies, so applicant included in new claims 34 and 40 a limitation describing the extracellular binding domain as comprising heavy chain and light chain variable regions. The claims now also specify that the extracellular binding domain binds to the heavy chain constant region of the antibody, but does not bind to an otherwise identical heavy chain constant region that lacks both the substitutions of (1) and the deletion of (2). These limitations fully address the Office's concerns that the claims, prior to the present amendment, encompassed extracellular domains that bind to other types of Fc mutations or even to wild-type Fc domains.
Applicant’s arguments have been fully considered but they are only partially persuasive. In view of the claim amendments and applicant’s arguments, the rejections over “treating a cancer in a subject in need of treatment” and “a mutated antibody that is an IgG antibody” are hereby withdrawn. However, the claims still encompass a broad genus of chimeric receptors with extracellular binding domain capable of binding to mutated antibody with mutations comprising mutations at EU numbering positions 235, 236, and 239 including one or more of the following substitutions: arginine at EU numbering position 235, arginine at EU numbering position 236, and lysine at EU numbering position 239, or at EU numbering positions 446 and 447. The specification does not provide support for the claimed genus.
As set forth above, the specification discloses only one binding domain (antibodies) which can bind a specific silent-Fc domain (235R/236R/239K) of SEQ ID NO: 3; and only one binding domain (antibodies) can bind a specific Delta GK-Fc (446/447 double deletion) of SEQ ID NO: 5 ([1345], Example 2 and Table 6). The specification discloses only one binding domain (antibodies for 235R/236R/239K) which can be used in the claimed method (Examples 5 and 6). The specification does not teach other extracellular binding domain (e.g. other antibody) which can bind to any other mutations encompassed by the claims. As set forth above, these two antibodies does not teach other antibodies which can bind to the same mutated Fc, or antibodies which can bind to other mutated Fc domains encompassed by the claims.
In addition, antibodies, which bind to mutated Fc domain, may also bind to wild-type Fc domain, depending on the epitope of the antibodies. Without knowing the relationship between the extracellular binding domain (e.g. antibody) structure and the binding specificity to mutated Fc domain, one of ordinary skill in the art would not be able to quickly visualize or recognize “an extracellular binding domain” which can be used in the claimed method because binding specificity is critical for the function of extracellular binding domain. Claims recite the extracellular binding domain binds to the heavy chain constant region of the antibody with claimed mutations, but does not bind to an otherwise identical heavy chain constant region that lacks both the substitutions of (1) and the deletion of (2). However, the specification does not show that the two disclosed antibodies (SKA0009 and YG55) have the binding specificity. Taken together, the specification does not describe representative number of species of the genus or establish the relationship between the structure of the extracellular binding domain and the claimed function.
Thus, the rejection is maintained for the reasons of record.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHENG LU whose telephone number is (571)272-0334. The examiner can normally be reached Monday-Friday 8-5.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571)270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/CHENG LU/Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
Prosecution Insights