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 .
Claim Status
Claims 3-4, 11-12, and 19-20 are cancelled. Claims 1-2, 5-10, 13-18, and 21-25 are pending and under examination.
Priority
This application is a national stage entry of PCT/JP2022/029854 filed on 8/3/2022, which claims priority from Japanese application JP2021-128012 filed 8/4/2021.
Information Disclosure Statements
The information disclosure statements filed on 5/14/2024 and 5/19/2025 have been considered by the examiner. In regards to the IDS from 5/19/2025, the size fee assertion statement is found in the transmittal letter filed on 5/19/2025.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-2 and 5-8 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a product of nature. These claims are to an agent with progesterone or a derivative thereof as an active ingredient, for use in combination treatment with an anti-human PD-L1 monoclonal antibody, where “for use in combination treatment with an anti-human PD-L1 monoclonal antibody” is an intended use statement without actually introducing the monoclonal antibody into the agent. Thus, the claim encompasses the naturally occurring compound progesterone or any of its naturally occurring derivatives. Claims 2, and 5-6 are only to functions of the progesterone or its derivative when in use and don’t alter the structure of the progesterone or its natural derivatives. Claims 7 and 8 are limitations of the antibody, which is only part of the intended use phrase from claim 1, on which these claims depend (directly or indirectly). Since the claims to the agent may only encompass progesterone or a natural derivative of progesterone, it reads on a naturally occurring product. The functional language or intended use statement do not add more to the product of nature of these claims.
Claim Rejections - 35 USC § 112(a) – Scope of Enablement – human PD-L1 monoclonal antibodies
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 1, 2, 5-7, 9, 10, 13-15, 17, 18, 21-23 and 25 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 atezolizumab or other species of human PD-L1 monoclonal antibodies applicant might provide in the specification, does not reasonably provide enablement for the entire genus of human PD-L1 monoclonal antibodies or their humanized versions that represent numerous, various sequences. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims. Human PD-L1 monoclonal antibodies allows for a large number of diverse possibilities of antibodies that could target human PD-L1. Humanized suggests the sequence is altered so they have a sequence that has more human characteristics for use in human.
Although applicant discusses the general making of monoclonal antibodies and there being sequences and fragments of sequences capable of binding PD-L1, applicant does not provide for particular sequences or fragment sequences towards human PD-L1. Thus, it does not appear enabled to make each and every antibody based on the various and diverse sequences that could be utilized from human PD-L1 (see pages 14-15 of applicant’s specification). Additionally, when considering humanization (page 15), this involves more possible alterations in sequences with no such sequences being provided by applicant.
An et al (bioRxiv, Sept 2022, doi: https://doi.org/10.1101/2022.09.10.507426, pages 1-20) teaches a novel monoclonal PD-L1 antibody (title and abstract). This represents such an antibody that was made after the filing of applicant’s application. Thus, not all such antibodies had yet been made. An’s newly developed antibody is noted to outcompete FDA-approved immune checkpoint inhibitors (page 12 of An and Conclusions).
Applicant does provide for particular antibodies with naming atezolizumab, avelumab and durvalumab (page 15). However, this is only 3 antibodies of this entire genus of possibly thousands of antibodies each having unique sequences and binding unique targets of human PD-L1.
One of skill in the art is an immunologist or an oncologist that specializes in immunotherapies.
As applicant does not provide a range of sequences for monoclonal antibodies and fragments thereof that bind to PD-L1, the art recognizes new PD-L1 antibodies being made after applicant’s filing and there are only three species of monoclonal antibodies provided for PD-L1 listed by applicant, applicant does not have a full scope of enablement for all such monoclonal antibodies and fragments thereof that could bind PD-L1 as there would be undue experimentation by one of skill in the art to make and test all the antibodies and fragments that could be created for the PD-L1 sequence to find those that are indeed able to bind PD-L1. However, applicant does have enablement for those listed in their specification, which are atezolizumab, avelumab and durvalumab.
Claims 1-2, 5-10, 13-18, and 21-25 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 progesterone and its particular species of derivatives that might be provided in the specification (see the particular species in paragraph 14), does not reasonably provide enablement for the entire genus of progesterone derivatives, which may encompass various structures with various functions. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims. The claims cover progesterone derivatives, and notes them as any natural or synthetic form and that they include derivatives of progesterone or testosterone and a derivative of another molecule or compound having progestogen activity (page 12 of specification). Page 12 of the specification also provides that a derivative refers to a chemical substance made of or providing a parent compound generated through one or a plurality of chemical reactions, which broadly encompasses a large possible genus of compounds made by various chemical processes and in a number of different ways (different variations of combinations with various addition groups or modifications).
Scherbakov et al (Invest New Drugs, 2023, volume 41, pages 142-152) teaches novel pentacyclic derivatives and benzylidenes of the progesterone series (title and abstract and Conclusion). These represent derivatives of progesterone that hadn’t been invented by the time of applicant’s filing.
Applicant does provide for a group of compounds/progestins that are species of derivatives (paragraph 14 of specification). All of these with the exception of “derivative of 19-nortestosterone” would be enabled.
As applicant provides for a very broad definition of what a derivative of progesterone can be which allows them to extend beyond the species that applicant presents, art after applicant’s filing presents new derivatives of progesterone and applicant provides a limited number of species for the progestin, applicant does not have full enablement for all derivatives of progesterone as there would be undue experimentation to make and use all the derivatives of progesterone. However, applicant does have enablement for those particular species of derivatives of progesterone such as hydroxyprogesterone caprate and medroxyprogesterone acetate that are in the specification.
Claim Rejections - 35 USC § 102
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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1, 2, 5-10, and 13-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Yoshie et al (Partial translation, Establishment of a humoral immunity evaluation system based on the pregnant immunity system, 2-19-2021, In applicant’s IDS).
Claims 2, 5-6, 10, and 13-14 are functions provided by the progesterone. If the prior art teaches progesterone, it will provide for these effects.
Yoshie teaches that progesterone plays an important role in allo suppression (page 3 of translation). Yoshie teaches antibody producing ability is frequently maintained by P4 (progesterone) treatment (top of page 4). Yoshie et al decided to analyze effects of COR and P4 (the steroids) on the immune system (page 3). Yoshie teaches that they are studying nivolumab as well as Atezolizumab and making conjugates with steroids (bottom of page 6). Yoshie provides establishment of an immune assessment system using individual patient’s PB by using IL-4, progesterone, PZP, and other pregnancy-related molecules required for becoming Th2 dominant in pregnancy could be largely achieved (page 7). Therefore, for claims 9-10 and 13-16, it is anticipated that progesterone/P4 will be conjugated (combined) with the antibody, Atezolizumab in the research of Yoshie. In regards to claims 1, 2 and 5-8, the teaching of progesterone is sufficient for anticipation. It is noted that Yoshie recognizes its immune system effects.
Claim(s) 1, 2, 5-10, and 13-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Du US 20250319100 (earliest effective date of 3-11-2021).
Claims 2, 5-6, 10, and 13-14 are functions provided by the progesterone. If the prior art teaches progesterone, it will provide for these effects.
Du teaches a composition with hydroxyprogesterone caproate and a monoclonal antibody against PD-1 or PD-L1 as an additional therapeutic (abstract). Claim 5 of Du provides for atezolizumab (also paragraphs 11 and 12). Claim 4 provides for a monoclonal antibody targeting PD-1 or PD-L1 (claim 4 of Du).
Claim Rejections – 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 17-18 and 21-25 are rejected under 35 U.S.C. 103 as being unpatentable over Yoshie et al (Partial translation, Establishment of a humoral immunity evaluation system based on the pregnant immunity system, 2-19-2021, In applicant’s IDS) and Suzuki et al (Drug Deliv Systems, 2004, volume 19, pages 539-545, In applicant’s IDS).
Yoshie teaches the claims as discussed above with providing a combination of progesterone with an anti-PD-L1 antibody, Atezolizumab. Yoshie’s studies are to provide tailor-made immunotherapies for cancer (last paragraph on page 7 of Yoshie translation, applicant provided).
Yoshie does not teach the immunoliposome form with the antibody bound to the membrane of the liposome.
Suzuki teaches PEG-liposomes for targeting using a surface modified with antibody that would be effective drug carriers (abstract in English, provided by applicant). Suzuki teaches its formed immunoliposomes for tumor therapy (abstract). Since they are drug carriers, this provides pharmaceutical formulations.
One of ordinary skill in the art before the time of filing would have included the atezolizumab antibody on the surface of a liposome for targeting while also including the progesterone for its useful immune system effects when developing a formulation to better treat cancers/tumors based on the combined teachings of Yoshie and Suzuki in forming a liposome carrier form that combines both the antibody and the progesterone. Therefore, there was a reasonable expectation of success of combining the teachings of the references to provide the immunoliposome formulations of atezolizumab (a PD-L1 monoclonal antibody) and also having progesterone (an immune-modulator) to make an effective immunotherapy for cancer.
Claims 17-18 and 21-25 are rejected under 35 U.S.C. 103 as being unpatentable over Du US 20250319100 and Suzuki et al (Drug Deliv Systems, 2004, volume 19, pages 539-545, In applicant’s IDS).
Du teaches a composition with hydroxyprogesterone caproate and a monoclonal antibody against PD-1 or PD-L1 as an additional therapeutic (abstract). Claim 5 of Du provides for atezolizumab (also paragraphs 11 and 12). Claim 4 provides for a monoclonal antibody targeting PD-1 or PD-L1 (claim 4 of Du) and Du provides for targeted therapeutic agents (paragraph 10). Du teaches its methods are to treat cancers (abstract).
Du does not teach the immunoliposome form with the antibody bound to the membrane of the liposome.
Suzuki teaches PEG-liposomes for targeting using a surface modified with antibody that would be effective drug carriers (abstract in English, provided by applicant). Suzuki teaches its formed immunoliposomes for tumor therapy (abstract). Since they are drug carriers, this provides pharmaceutical formulations.
One of ordinary skill in the art before the time of filing would have included the atezolizumab antibody on the surface of a liposome for targeting while also including the hydroxyprogesterone caproate for its useful immune system effects when developing a formulation to better treat cancers/tumors based on the combined teachings of Du and Suzuki in forming a liposome carrier form that combines both the antibody and the hydroxyprogesterone. Therefore, there was a reasonable expectation of success of combining the teachings of the references to provide the immunoliposome formulations of atezolizumab (a PD-L1 monoclonal antibody) and also having hydroxyprogesterone caproate (an immune-modulator) to make an effective immunotherapy for cancer.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARK V STEVENS whose telephone number is (571)270-7080. The examiner can normally be reached M-F 9:00 am to 6:00 pm EST.
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/MARK V STEVENS/Primary Examiner, Art Unit 1613