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
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 May 4, 2026 has been entered.
Claim Status
Claims 12 and 18 have been amended.
Claims 4-5, 8-10, and 13 have been canceled.
Claims 1-3, 6-7, 11, and 14-17 were previously canceled.
Claims 12 and 18 are pending and under consideration.
Priority
This application is a 371 of PCT/JP2021/043538 filed November 29, 2021 which claims the benefit of foreign applications JAPAN 2020-198044 filed November 30, 2020 and JAPAN 2021-110912 July 2, 2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Applicant is reminded that support for the claimed invention cannot be determined because the foreign priority documents provided for JP2020-198044 and JP2021-110912 are not in English.
Claim Rejections - 35 USC § 112(b)
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.
Claim 18 is rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 18 is drawn to a method for producing, selecting or identifying an antibody or antigen-binding fragment thereof. However, one of ordinary skill in the art would not know how to produce, select, or identify the instantly antibody because the claim does not recite any active, manipulative, or transformative steps.
Claim 18 recites the term “does not significantly react” which is a relative term that renders the claim indefinite. The specification defines does not significantly react as, for example does not react at all, or does not substantially react [pg. 28]. The term “does not substantially react” as recited in the specification, is also a relative term. Therefore the term “does not significantly react” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
For the purpose of examination, the claim is interpreted as an antibody or an antigen binding-fragment thereof that does not bind to HER2 expressed on a non-cancer cell.
Claim Rejections - 35 USC § 112(a)
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.
Enablement
Claim 12 is rejected under 35 U.S.C. 112(a) because the specification, while being enabling for producing, selecting or identifying an antibody or antigen-binding fragment thereof comprising a heavy chain CDR1 comprising the amino acid sequence of SEQ ID NO: 24, a heavy chain CDR2 comprising the amino acid sequence of SEQ ID NO: 25, a heavy chain CDR3 comprising the amino acid sequence of SEQ ID NO: 26, a light chain CDR1 comprising the amino acid sequence of SEQ ID NO: 27, a light chain CDR2 comprising the amino acid sequence of SEQ ID NO: 28, and a light chain CDR3 comprising the amino acid sequence of SEQ ID NO: 29; does not reasonably provide enablement for treating cancer as broadly claimed.
The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed most recently in Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008). See also In re Cortright, 49 USPQ2d 1464, 1466 and Bristol-Myers Squibb Co. v. Rhone-Poulenc Rorer Inc., 49 USPQ2d 1370.
The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: (1) the nature or the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. When the above factors are weighed, it is the examiner’s position that one skilled in the art could not practice the invention without undue experimentation. Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444.
(1) The nature of the invention and (5) The breadth of the claims:
Claim 12 is drawn to a method for treating cancer in a subject in need thereof, comprising administering an effective amount of a pharmaceutical composition comprising the instantly claimed antibody or an antigen-binding fragment thereof.
Claim 12 is broad and inclusive of all types of all types of cancer in humans generally.
The breadth of the claims exacerbates the complex nature of the subject matter to which the present claims are directed. The claims are extremely broad due to the vast number of possible cancer types represented by the terms “treating cancer”. Cancer is not a single disease, or cluster of closely related disorders. There are hundreds of cancers, which have in common only some loss of controlled cell growth. Cancers are highly heterogeneous at both the molecular and clinical level, and can occur in most parts of the body. The following are examples of some of the major classes of cancer, each having numerous types:
CNS cancers
Leukemias
Carcinomas of the liver
Lung and pleural cancers
Thyroid cancers
Melanomas
Colorectal cancers
Renal carcinomas
Prostate cancers
Breast cancers
Ovarian and uterine cancers
Testicular cancers
Esophageal cancers
Cervical cancers
Cardiothoracic cancers
Bladder cancers
(2) The state of the prior art and (4) The predictability or unpredictability of the art:
The state of the art teaches there is no known antibody that can treat all types of cancer. The art of cancer treatment and antibody development involves a very high level of unpredictability. While the state of the art is relatively high with regard to the treatment of specific cancers with antibodies against specific targets, there is no one treatment for all cancers broadly. The lack of significant guidance from the present specification or prior art with regard to the actual treatment of cancer in a subject, with the claimed active ingredient makes practicing the claimed invention unpredictable.
Fouad (2025) teaches selectivity in therapeutic antibody design is crucial to ensure that antibodies bind specifically to their intended targets while minimizing off-target effects. The antibody must discriminate between one epitope in one cellular or tissue context and the same epitope in another cellular or tissue context. While specificity is its ability to discriminate one epitope from other similar epitopes. Preclinical strategies to leverage selectivity are primarily based on the detection of unique features of tumor cells, or the tumor microenvironment, or specific external stimuli. Epitope selection and mapping to identify unique targets that are disease-associated and absent in normal tissues is a critical step in development. Detection of mutated or overexpressed protein present on the cell surface and designing antibodies that recognize and bind tumor-specific antigens or mutated residues is one approach. Another approach is to target cryptic or conformational epitopes that form structural conformations found only in diseased cells [pg. 23654].
Claim 12 recites the six CDR amino acid sequences of an antibody, however, the antibody target and type of cancer(s) to be treated is not disclosed. Scheffer et al. (2024) teaches determining the target cancer type from an antibody CDR sequence is a complex process involves identifying the specific antigen it binds to, which is achieved through bioinformatics, sequence homology searching, and structural modeling. Once the antigen (e.g., HER2) is identified through these methods, the corresponding cancer type (e.g., breast cancer or colon cancer) can be determined based on which cells express that marker [Introduction].
Given the lack of predictability in treating cancer, one of skill in the art would have to engage in undue experimentation to first identify individuals to which the instant method would apply.
6) the amount of direction or guidance provided by the inventor; 7) the existence of working examples;
The instant specification sets forth examples demonstrating the instantly claimed antibody binds to HER2 expressed on SK-BR-3 breast cancer cells, but does not bind to HER2 expressed on normal human epidermal keratinocyte cells. In addition, the antibody also recognizes breast cancer cells that have been diagnosed as HER2 negative [Example 3, [0098]]. However, there is no in vitro or in vivo data demonstrating the instantly claimed antibody can be used as a treatment for cancer. Although antibody binding to cancer cells is necessary for targeting, it does not always translate into therapeutic success as efficacy depends on complex immune interactions. Factors such as tumor heterogeneity, immunosuppressive environments, and the inability to engage effector cells can limit results, making binding an insufficient predictor of clinical benefit. Therefore, one of skill in the art would be required to engage in extensive, difficult experimentation to identify what, if any, type of cancer that could be treated with the instantly claimed antibody. This required experimentation is undue.
In conclusion, the claimed invention does not provide enablement for treating cancer. Thus for the reasons outlined above, the specification is not considered to be enabling for one skilled in the art to make and use the claimed invention as the amount of experimentation required is undue, due to the broad scope of the claims, the lack of guidance and working examples provided in the specification. Therefore, the specification is not representative of the instant claims and the specification is not fully enabled for the instant claims. In view of the above, one of skill in the art would be forced into undue experimentation to practice the claimed invention.
Double Patenting
Pursuant to 37 CFR 1.78(f), when two or more applications filed by the same applicant or assignee contain patentably indistinct claims, elimination of such claims from all but one application may be required in the absence of good and sufficient reason for their retention during pendency in more than one application. Applicant is required to either cancel the patentably indistinct claims from all but one application or maintain a clear line of demarcation between the applications. See MPEP § 822.
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.
Double Patenting - Maintained/Updated
The following are updated grounds of rejection necessitated by Applicant’s claim amendments filed May 4, 2026. Applicant’s arguments relevant to the updated grounds of rejection will be addressed below.
Claims 12 and 18 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of U.S. Patent No. 12,122,846, in view of Mathieu et al. (US 2018/0094056) (“Mathieu”).
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims are drawn to the identical anti-HER2 antibody CDR amino acid sequences recited in the instant claims.
Specifically, the issued patent recites an antigen binding domain recognizing HER2 comprising VH CDRs comprising the amino acid sequences CDR1 of SEQ ID NO: 1, CDR2 of SEQ ID NO: 2, and CDR3 of SEQ ID NO: 3; and VL CDRs comprising the amino acid sequences CDR1 of SEQ ID NO: 4, CDR2 of SEQ ID NO: 5, and CDR3 of SEQ ID NO: 6 which are 100% identical to the instantly claimed VH CDRs comprising the amino acid sequences CDR1 of SEQ ID NO: 24, CDR2 of SEQ ID NO: 25, and CDR3 of SEQ ID NO: 26; and VL CDRs comprising the amino acid sequences CDR1 of SEQ ID NO: 27, CDR2 of SEQ ID NO: 28, and CDR3 of SEQ ID NO: 29.
The instant claims differ from the issued claims in that they do not explicitly teach pharmaceutical compositions, methods for antibody selection, or treatment of cancer.
As set forth in the Office action mailed February 10, 2025, Mathieu teaches anti-HER2 antibodies and antibody fragments, such as scFvs [0014-0015] for the treatment of a HER2 positive cancer [0290]. The antibody can be formulated in a pharmaceutical composition [0282]. Mathieu carried out a series of binding assays with human PBMCs to test the antibodies affinity for their HER2 target [0334].
It would have been obvious to one of ordinary skill in the art that the antibody-binding fragment disclosed in the issued patent could be formulated as a pharmaceutical composition for the treatment of cancer as evidenced by Mathieu. A skilled artisan would be able to use a number of binding assays to screen anti-HER2 antibodies generated from the amino acid sequences disclosed by the issued patent. As such, the instant claimed invention is an obvious modification of the claims of the issued patent in view of Mathieu.
Response to Arguments
Applicant has argued on page 5 of the reply received May 4, 2026, that the nonstatutory double patenting rejections of the instant claims over the claims 1-2 of US Patent No. 12,122,846 should be withdrawn because the issued claims are directed to a CAR and do not disclose the presently claimed methods. Further, Applicant argues that at the time of filing the instant invention the CDR sequences were not known. Therefore, one of ordinary skill in the art would have had no reason to use the sequences disclosed in the issued patent in combination with the methods taught by Mathieu.
Applicant’s arguments were considered, but they were not deemed persuasive.
The issued patent is directed to a CAR comprising an antigen-binding domain against HER2 comprising the identical CDR regions as the antibody recited in the instant claims. Claim 2 of the issued patent discloses the antigen-binding fragment is an scFv.
The instant claims are drawn to an anti-HER2 antibody or antigen-binding fragment thereof. The instant specification discloses antibody-binding fragments may be in the form of an scFv [0018] and the antibody or antigen-binding fragment can be used to target cancer cells [0033].
The function of the CAR disclosed in the issued patent is to target cells expressing HER2 comprising the identical antigen-binding fragment recited in the instant claims. As such, the claims of the issued patent anticipate the presently claimed invention, and the rejection is maintained.
MPEP § 804(II) states 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).
Applicant’s arguments regarding the amino acid sequences are irrelevant, as the nonstatutory double patenting doctrine prevents the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. 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).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAUREEN DRISCOLL whose telephone number is (571) 270-0730. The examiner can normally be reached Monday through Friday.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached on (571) 270-3503. The fax phone number for the organization where this application or proceeding is assigned is (571) 273-8300.
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/MAUREEN VARINA DRISCOLL/ Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
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