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/JP2021/034438 (filing date 09/17/2021), which claims the benefit of the prior-filed Japanese Provisional Patent Application No. JP2020-157900 (filing date 09/18/2020).
Status of Application/Claims
The preliminary amendment, filed 04/19/2023, in which claims 1-7 were modified, is acknowledged. Claims 1-7 are original. Claim 8 is newly added. Claims 1-8 are currently pending and are examined on the merits herein.
Information Disclosure Statements
The information disclosure statements (IDSs) submitted on 03/17/2023 and 12/31/2024 have been fully considered by the examiner.
Specification
The use of the terms Chiron, Proleukin, Roche, Zenapax, Novartis, Simulect, PrimeScript, Takara Bio, Thermo Fisher Scientific, PrimeSTAR, NEB, NucleoBond, Opti-MEM, GlutaMAX, ExpiFectamine, Life Technologies, Techno Plastic Products AG, GE Healthcare, Unicorn, Gibco, Applied Biological Materials Inc., NanoLuc, Promega, Hyclone, BioLegend, FujiFilm, CellTiter-Glo, Genevac, SP Scientific, Taitec Corporation, Sigma-Aldrich, Miltenyi Biotec, and Nano-Glo, which are trade names or marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appears 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.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
Amino acid SEQ ID NOs missing:
p.21, line 28
p.28, line 23, line 30
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
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 8 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim 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.
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: (1) The nature of the invention; (2) The breadth of the claims; (C) The amount of direction provided by the inventor; (D) The existence of working examples; (E) The state of the prior art; (F) The level of predictability in the art; (G) The quantity of experimentation needed to make or use the invention based on the content of the disclosure and (H) 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 8 is drawn to a method for preventing cancer, respectively.
The breadth of the claims
The claim is broad in that it encompasses the prevention of any cancer.
The claim is broad and inclusive of all types of cancer. The breadth of the claim exacerbates the complex nature of the subject matter to which the present claims are directed. 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, something seen especially in, for example, the cancers of the breast, brain and salivary glands. They can occur in pretty much every part of the body. For example, there are solid cancers of the brain, spine, live, prostate, testes, ovaries, bile duct, blood vessels, lung and pleural cavity, thyroid, skin (including melanoma), colon, prostate, kidneys, breasts, testicles, vulva and vagina, uterus, cervix, fallopian tubes, thymus, stomach, esophagus, spleen, salivary glands, heart, oral cavity, adrenal glands, eye, head and neck, bladder, bone, and gall bladder. Each of these types of cancer have potentially dozens of sub-categories that each have unique physiological and etiological characteristics.
The amount or direction provided by the inventor/ the existence of working examples
The examples of the instant disclosure are limited to studies assessing the treatment of existing cancer in mice. Figs. 20-24 show assessments of tumor size and immune cell presence in tumor-bearing mice.
The examples provided do not demonstrate the prevention of tumors. Additionally, the disclosure does not discuss, or demonstrate through working examples, a method that could be used to determine that cancer was prevented using the claimed agents as there is no disclosed method to determine that cancer would have predictably occurred without treatment.
The state of the prior art/ the level of predictability in the art
There are no art recognized methods that could be used to establish that the cancer was prevented using the claimed therapeutic pharmaceutical or 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, Ahhmadzada et al. also recognize that the heterogeneity of NSCLC remains a key barrier to accurate molecular classification and necessitates individualization of treatment (p.8).
Beans. Targeting metastasis to halt cancer’s spread PNAS (2018), 115:50, p.12539-12543 (herein referred to as Beans) teaches that across cancer types, 90% of cancer deaths are caused not by the primary tumor but by metastasis (i.e., tumors that develop distal to the primary tumor/therapeutic agent administration site). Beans teaches that although some drugs may shrink metastases along with primary tumors, no existing drugs treat or prevent metastasis directly (p.12540). Beans states “Without a targeted approach, metastatic tumors often reemerge. We shrink them, we send them back to their residual state, and they reenact those survival functions and retention of regenerative powers that made them metastasis-initiating cells in the first place.” Beans teaches that one of the major scientific challenges of studying metastatic disease is that different forms of cancer seem to metastasize through different mechanism and the same form of cancer may metastasize differently in different subsets of patients (p.12542). Of note, Beans states, “It’s unlikely that one researcher is going to find one pathway that proves to be the key to metastasis” (p.12542). Beans also teaches that translating many findings into therapies also presents unique hurdles in that it is difficult to measure the effectiveness of the therapy. Secondary tumors are often miniscule, and therefore, measuring success by tumor shrinkage may not work. Measuring the incidence of metastasis after treatment is also more difficult (p.12542).
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).
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 the tumors were prevented using the claimed pharmaceutical and method. 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 recurrence 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, instant claims 7 and 8 are determined to not meet the scope of enablement requirement of 35 U.S.C. 112(a).
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Deak, et al. Immunoconjugates – US20180326010, herein referred to as Deak.
Deak teaches immunoconjugates comprising mutant IL-2 and an antibody (i.e., an immunoglobulin; instant claim 2), wherein the antibody comprises an Fc domain (abstract; figure) and pharmaceutical compositions thereof (abstract; p.63, [0241]) (instant claims 1-3 and 6). Deak teaches that the intermediate affinity IL-2 receptor consists of the β and γ receptor subunits that is expressed on resting effector cells; while, the high-affinity IL-2 receptor is a trimer that also comprises the α receptor subunit (p50, [0130]). Deak teaches that the IL-2 mutant comprises at least one amino acid mutation that abolishes or reduces affinity of the mutant IL-2 polypeptide to the α subunit of the IL-2 receptor and preserves affinity of the mutant to the intermediate-affinity (i.e., β/γ receptor) compared to WT IL-2 (p.50, [0131]; instant claim 5). Deak further teaches that IL-2 mutations that reduce affinity to the IL-2 α receptor (i.e., CD25) include amino acid substitutions K35A, R38A, F42A, and Y45A (p.50, [0132]; instant claim 1). Additionally, Deak conceives of IL-2 conjugates that are fused to another moiety such as albumin which results in extended half-life (i.e., “albumin-IL2”; p.52, [0150]; instant claims 2 and 4). Deak teaches that the IL-2 conjugates may be used as immunotherapeutic agents for treatment of cancer (p.64, [0250]; instant claims 7-8).
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached at 571-272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JAMI MICHELLE GURLEY/Examiner, Art Unit 1647
/JOANNE HAMA/ Supervisory Patent Examiner, Art Unit 1647