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 .
Priority
The instant application is a 35 U.S.C. 371 national phase application, and claims
priority to, International Application No. PCT/KR2021/010945, filing date 08/18/2021.
This PCT application claims priority to Korean Application No. KR10-2020-0103270
filed 08/18/2020. Receipt is acknowledged of certified copies of papers required by 37
CFR 1.55.
Applicant is notified that to obtain the benefit of foreign priority under 35 U.S.C.
119(a)-(d) prior to declaration of an interference, a certified English translation of the
foreign application KR10-2020-0103270 must be submitted in reply to this action. 37
CFR 41.154(b) and 41.202(e). Failure to provide a certified translation may result in no
benefit being accorded for the non-English application.
This correction is required to perfect priority (MPEP 216.01).
Status of Application/Claims
The preliminary amendment, filed 02/18/2024, is acknowledged. Claims 1-19 are canceled. Claims 20-34 are new. Claims 20-34 are currently pending and are examined on the merits herein.
Information Disclosure Statements
The information disclosure statements (IDSs) submitted on 02/18/2024 has been fully considered by the examiner.
Specification
The use of the terms Invitrogen, Keytruda, Abcam, Charles River, Dako, and GraphPad, which are trade names or marks used in commerce, have been noted in this application. The terms should be in all caps wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
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.
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 20-34 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.
Regarding instant claims 20-34, the claims are inclusive of a genus of antibodies (claim 28) and bispecific antibodies (claim 20) that comprise anti-B7-H4 antibodies. The disclosure supports structures for 5 anti-B7-H4 antibodies wherein the 6 CDRs required for antigen binding are defined: 16E3H3hu, 16E3H3 M1, 16E3H3m, 23B6C2, and 73B4F10 (see Tables 1-4). Claims 20 and 28, however, are inclusive of anti-B7-H4 antibodies wherein the recited CDRs 1-3 for the heavy and light chains are interchangeable and can be combined in any combination. Thus, the specification does not disclose, and the art does not teach, structures for the genus of antibodies with the claimed antibody function as is broadly encompassed in the claims. Claims 21-27 and 29-34 are dependent on claims 20 and 28, respectively, and do not overcome the issue, and are thus also rejected.
Regarding instant claims 20-27, the claims are inclusive of a genus of anti-41BB antibodies. The disclosure supports structures for 7 anti-41BB antibodies wherein the 6 CDRs required for antigen binding are defined: 1A10, 1A10M4, 1A10M11, 1A10M12, 1A10M13, 1A12, and 1A12M1 (see Tables 5-8). Claim 20, however, is inclusive of anti-41BB antibodies wherein the recited heavy and light chains comprising the heavy chain CDRs and light chain CDRs can be combined in any combination. Thus, the specification does not disclose, and the art does not teach, structures for the genus of antibodies with the claimed antibody function as is broadly encompassed in the claims. Claims 21-27 are dependent on claims 20 and do not overcome the issue, and are thus also rejected. Further, the disclosure does not provide for a genus of bispecific antibodies wherein any of the 5 anti-B7-H4 antibodies can be comprised within the same bispecific antibody with any of the 7 supported anti-41BB antibodies. The disclosure only reasonably provides support for a single bispecific antibody: B10317 (16E3H3 x 1A10 M12; see Tables 23-24).
Regarding claims 25-27 and 32-34, the claims are drawn to a method of treating a disease related to B7-H4, 41BB, or both (claims 25-27) or B7-H4 (claims 32-34) by administering the aforementioned antibodies. While the disclosure provides structures for the aforementioned 6 anti-B7-H4 antibodies, 7 anti-41BB antibodies, and 1 bispecific antibody, the disclosure does not reasonably provide support that all structures for antibodies treat any disease. The disclosure supports that the 16E3H3 M1 anti-B7-H3 antibody binds cancer cells and promotes IFNγ T cell secretion (Fig.3-5). The disclosure also supports that the B10317 (16E3H3 M1 + 1A10 M12) bispecific antibody binds cancer cells and promotes IFNγ T cell secretion, cancer cell lysis, and anti-tumor activity (Fig.6-17). Claims 26-27 and 33-34 are dependent upon claims 20 and 28, respectively, and do not resolve the issue. Further, no disease other than cancer was assessed by the examples in the disclosure.
In regards to claims to a product defined by function, without a correlation between structure and function, the claims do little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement.
The state of the prior art is such that it is well established in the art that the formation of an intact antigen-binding site of antibodies generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs or hypervariable regions, which provide the majority of the contact residues for the binding of the antibody to its target epitope (see Paul. Fundamental Immunology, 3rd Edition, 1993, pp. 292-295; herein referred to as Paul). The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity, which is characteristic of the immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites (p.293, col.1-2, lines 3-8, line 31, and lines 27-30).
The instant specification fails to provide sufficient descriptive information, such as definitive structural features that are common to the genus. That is, the specification provides neither a representative number of antibodies that encompass the genus of antibodies with the claimed function nor does it provide a description of structural features that are common to the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species.
The “claims merely recite a description of the problem to be solved while claiming all solutions to it and . . . cover any compound later actually invented and determined to fall within the claim’s functional boundaries— leaving it to the pharmaceutical industry to complete an unfinished invention.” Ariad Pharmaceuticals, Inc. v. EliLilly and Co.,598 F.3d 1336, 1353 (Fed. Cir. 2010).
Because the disclosure fails to describe common attributes or characteristics that adequately identify members of the genera, and because the genera of anti-B7-H4 antibody and anti-B7-H4/anti-41BB bispecific antibody are highly variant, the disclosure of anti-B7-H4 antibodies (16E3H3hu, 16E3H3 M1, 16E3H3m, 23B6C2, and 73B4F10), anti-41BB antibodies (1A10, 1A10M4, 1A10M11, 1A10M12, 1A10M13, 1A12, and 1A12M1), and the B10317 bispecific antibody is insufficient to describe the genera. Thus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genera as broadly claimed.
Claims 25-27 and 32-34 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treatment of disease, does not reasonably provide enablement for prevention of disease. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. THIS IS AN ENABLEMENT REJECTION.
Enablement is considered in view of the Wands factors (MPEP 2164.01(a)). The court in Wands states: “Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is ‘undue,’ not ‘experimentation.’” (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations.” (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: The nature of the invention; the breadth of the claims; the amount of direction provided by the inventor; the existence of working examples; the state of the prior art; the level of predictability in the art; the quantity of experimentation needed to make or use the invention based on the content of the disclosure; and, the level of one of ordinary skill. While all of these factors are considered, a sufficient amount for amount for a prima facie case are discussed below.
The nature of the invention
Claim 25 is drawn to preventing or treating a disease related to B7-H4, 41BB, or both. Claims 26-27 are dependent on claim 25 and do not overcome the issue.
Claim 32 is drawn to preventing or treating a disease related to B7-H4. Claims 33-34 are dependent on claim 32 and do not overcome the issue.
The breadth of the claims
Claims 25 and 32 are broad in that the claims are inclusive of prevention of any disease related to B7-H4 and/or 41BB. Claims 26-27 are dependent on claim 25 and do not overcome the issue; claims 33-34 are dependent on claim 32 and do not overcome the issue.
The level of one of ordinary skill
Regarding claims 25-27 and 32-34: The level of skill of one skilled in this art is high.
The amount or direction provided by the inventor/ the existence of working examples
Regarding claim 25 (and, thus, also claims 26-27), the specification teaches administration of the bispecific anti-B7-H4/anti-41BB antibody for the treatment of (T26-28, Figs.7-17). The disclosure supports bispecific anti-B7-H4/anti-41BB antibody
Regarding claim 32 (and, thus, also claims 33-34), the specification teaches administration of the bispecific anti-B7-H4 antibody for the treatment of (T26-28, Figs.3-4). The disclosure supports anti-B7-H4 cancer cell binding (Fig.8) and IFNγ T cell secretion (Fig.10-17) for the “B10317” species, which is defined by the bispecific antibody comprised of the “16E3H3 M1/M40413” anti-B7-H4 antibody (p.101-102) and the “A10 M12” anti-41BB antibody (p.101-102; p.113, para.1).
The disclosure does not otherwise provide support that any species of bispecific antibody or anti-B7-H4 antibody is able to prevent a disease.
The state of the prior art/ the level of predictability in the art
The state of the prior art at the time of the effective filing date supports that not all diseases can be prevented. For example, regarding cancer: There are no art recognized methods that could be used to establish that cancer was prevented using the claimed therapeutic method. Additionally, there are no art recognized methods that could be used to identify subjects who would have predictably developed cancer in order to determine that the cancer was prevented using the claimed methods.
Ahmadzada et al. An update on predictive biomarkers for treatment selection in non-small cell lung cancer. Journal of Clinical Medicine (2018), 7:153, p.1-12 (herein referred to as Ahmadzada) suggests that it is still difficult to apply classification of cancers to select targeted therapies. For example, Ahmadzada teaches that non-small cell lung cancer is a highly heterogeneous disease that develops from genetic mutations and gene expression patterns that initiate uncontrolled cellular growth, proliferation, and progression (p.2). Ahmadzada also teaches that only 15-25% of non-small cell lung cancer patients benefit from immunotherapy, suggesting the need for novel biomarkers to identify the best candidates for treatments (p.7). Further, Ahmadzada et al. also recognize that the heterogeneity of NSCLC remains a key barrier to accurate molecular classification and necessitates individualization of treatment (p.8)
The American Cancer Society maintains that “There's no sure way to prevent cancer, but you can help reduce your risk by making healthy choices like eating right, staying active, and not smoking” (American Cancer Society. Cancer Risk and Prevention. 1/1/2025. Internet – Wayback Machine. p.1-4; herein referred to as ACS).
The quantity of experimentation needed to make or use the invention based on the content of the disclosure
Studies regarding treatment and prevention of cancer are underway that aim to improve earlier detection and better treatments for cancer. However, based on the disclosure and the prior art, there is no known or disclosed method through which an ordinarily skilled artisan would have been able to predictably identify subjects who would have predictably developed cancer in order to determine that cancer was prevented using the claimed methods. Therefore, in order to practice the invention as claimed, an ordinarily skilled artisan would have to participate in undue experimentation to determine a method that would allow for the prevention of cancer.
In view of the Wands factors discussed above, a person of ordinary skill in the art would have to engage in undue experimentation to practice the full scope of the claimed invention. As such, the instant claims were determined to not meet the scope of enablement requirement of 35 U.S.C. 112(a).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jami M Gurley whose telephone number is (571)272-0117. The examiner can normally be reached Monday - Friday, 8am - 4pm.
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/JAMI MICHELLE GURLEY/Examiner, Art Unit 1647
/JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
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