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
This application is a U.S. national phase of International Application No. PCT/JP2022/006843, filed on 02/21/2022. This application claims priority to Japan patent Application No. JP2021-031041, filed 02/26/2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Claim Status
The amendment, filed on 01/16/2024, in which claims 2-6 and 10 are amended and claims 1, 7-9, and 11-13 are canceled, is acknowledged. Claims 2-6 and 10 are pending in the instant application and are examined on the merits herein.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 09/29/2023 and 02/26/2025 have been considered by the examiner.
The information disclosure statement filed 08/09/2023 fails to comply with the provisions of 37 CFR 1.98 and MPEP § 609 because of the following reasons:
NPL-1 (IKEDA et al.) fails to comply with 37 CFR 1.98(a)(3)(i) because it does not include a concise explanation of the relevance, as it is presently understood by the individual designated in 37 CFR 1.56(c) most knowledgeable about the content of the information, of each reference listed that is not in the English language.
NPL-2 (NAKAJIMA et al.) fails to comply with 37 CFR 1.98(a)(2) because the copy provided is illegible.
The aforementioned references have been placed in the application file, but the information referred to therein has not been considered as to the merits. All other references where not lined through have been considered.
Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
The listing of references in the specification (¶ [0002], [0075], and [0083]) is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The following guidelines illustrate the preferred layout for the specification of a utility application. These guidelines are suggested for the applicant’s use.
Arrangement of the Specification
As provided in 37 CFR 1.77(b), the specification of a utility application should include the following sections in order. Each of the lettered items should appear in upper case, without underlining or bold type, as a section heading. If no text follows the section heading, the phrase “Not Applicable” should follow the section heading:
(a) TITLE OF THE INVENTION.
(b) CROSS-REFERENCE TO RELATED APPLICATIONS.
(c) STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT.
(d) THE NAMES OF THE PARTIES TO A JOINT RESEARCH AGREEMENT.
(e) INCORPORATION-BY-REFERENCE OF MATERIAL SUBMITTED ON A READ-ONLY OPTICAL DISC, AS A TEXT FILE OR AN XML FILE VIA THE PATENT ELECTRONIC SYSTEM.
(f) STATEMENT REGARDING PRIOR DISCLOSURES BY THE INVENTOR OR A JOINT INVENTOR.
(g) BACKGROUND OF THE INVENTION.
(1) Field of the Invention.
(2) Description of Related Art including information disclosed under 37 CFR 1.97 and 1.98.
(h) BRIEF SUMMARY OF THE INVENTION.
(i) BRIEF DESCRIPTION OF THE SEVERAL VIEWS OF THE DRAWING(S).
(j) DETAILED DESCRIPTION OF THE INVENTION.
(k) CLAIM OR CLAIMS (commencing on a separate sheet).
(l) ABSTRACT OF THE DISCLOSURE (commencing on a separate sheet).
(m) SEQUENCE LISTING. (See MPEP § 2422.03 and 37 CFR 1.821 - 1.825). A “Sequence Listing” is required on paper if the application discloses a nucleotide or amino acid sequence as defined in 37 CFR 1.821(a) and if the required “Sequence Listing” is not submitted as an electronic document either on read-only optical disc or as a text file via the patent electronic system.
The use of the terms “Seahorse” (pg 6, line 2; pg 8, line 3; ¶ [0072], lines 4 and 5), “FACSAria” (¶ [0067]), “Dynabeads” (¶ [0067]), “FACSCanto” (¶ [0068]), “FlowJo” (¶ [0068]), “Nucleospin” (¶ [0070] and [0071]), “ReverTra Ace” (¶ [0071]), “PowerUp” and “SYBR” (¶ [0071]), “Graph Pad Prism” (¶ [0073] and [0078]), which are trade names or marks used in commerce, have been noted in this application. Each term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
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 2-6 and 10 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.
To satisfy the written description aspect of 35 U.S.C. 112(a) for a claimed genus of molecules, it must be clear that: (1) the identifying characteristics of the claimed molecules have been disclosed, e.g., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics; or (2) a representative number of species within the genus must be disclosed. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Claim 10 is drawn to a method of treating cancer, infection or a combination thereof comprising administering a substance capable of enhancing TCR signaling before, after, or simultaneously with a PD-1 signaling inhibitor.
Claim 2 is drawn to the method of claim 10, wherein the substance capable of enhancing TCR signaling comprises a CD45 inhibitor and/or a cell.
MPEP 2173.05(g) teaches that "Unlimited functional claim limitations that extend to all means or methods of resolving a problem may not be adequately supported by the written description or may not be commensurate in scope with the enabling disclosure, both of which are required by 35 U.S.C. 112(a) and pre-AIA 35 U.S.C. 112, first paragraph. In re Hyatt, 708 F.2d 712, 714, 218 USPQ 195, 197 (Fed. Cir. 1983); Ariad, 598 F.3d at 1340, 94 USPQ2d at 1167. For instance, a single means claim covering every conceivable means for achieving the stated result was held to be invalid under 35 U.S.C.112, first paragraph because the court recognized that the specification, which disclosed only those means known to the inventor, was not commensurate in scope with the claim. Hyatt, 708 F.2d at 714-715, 218 USPQ at 197."
The instant specification does not provide an explicit definition of the scope of “enhancing TCR signaling” though discloses this enhancement can be confirmed by evaluating phosphorylation of ZAP-70 in CD8+ cells (¶ [0012]), subsequent dependent claim 2 recites the substance capable of enhancing TCR signaling is a CD45 inhibitor and/or a cell. The instant disclosure makes reference to two CD45 inhibitors (¶ [0015]; also recited in claim 3) and P4 cells (CD44lowCD62Llow) (¶ 0014]). By broadest reasonable interpretation of the claim these species are not commensurate in scope with a genus of substances capable of enhancing TCR signaling. For example, Rath (Cells. 2020;9(6):1485) reviews diverse engineering strategies that can be utilized to enhance anti-tumor activity including, but not limited to, TCR-Transgenic T cells including TCR framework engineering to enhance functional avidity of TCR-transgenic T cells, upregulation of adhesion molecules to enhance T cell-target cell interactions, and adding additional CD3 signaling chains to overcome limited availability in TCR-engineered T cells (pg 9, section 4.1).
The instant disclosure defines “PD-1 signaling” as referring to the signal transduction mechanism of PD-1 (¶ [0023]) and therefore inhibitors of this pathway can broadly include substances which specifically target PD-1 or its respective ligands (PD-L1 or PD-L2). The specification further discloses specific antibodies against PD-1 and PD-L1 known in the art (i.e. content with sufficient written description) (¶ [0024]). Given the sheer breadth of possible substances which would fall within the scope of the claim, applicant has not disclosed a representative number of species which would possess the claimed function of PD-1 signaling inhibition. For example, Patsoukis (Sci Adv. 2020;6(38):eabd2712) teaches that while current treatment paradigms dictate the use of blocking antibodies against the components of the pathway (i.e. receptor and ligands) there are also alternative mechanisms for regulating PD-1 signaling using interventions that target expression and function of PD-1 and PD-L1 (Table 1).
Overall, it is not evident by the disclosure, that applicant was in possession of an adequate number of species of which satisfy the breadth of the instant claims. Therefore, instant claim 10, and subsequent dependent claims 2-6 that do not cumulatively rectify the issues as discussed above, were determined not to meet the written description requirement of 35 USC 112(a).
Claim 10 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 specification, while being enabling for “treating a cancer”, does not reasonably provide enablement for “preventing a cancer.” 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.
Regarding the prevention of cancer, the America 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” (Cancer risk and prevention. American Cancer Society. Accessed January 22, 2025. https://www.cancer.org/cancer/risk-prevention.html. Internet – Wayback Machine). And, while dual CD45 and PD-1 inhibition have been shown to reduce tumor growth (Fernandez et al., Nature. 2020;586(7831):779-784) suggesting use in cancer treatment, there is no evidence in the prior art that utilizing combination CD45 and PD-1 inhibition enables cancer prevention without undue experimentation. See MPEP § 2146.01. Applicant can overcome this rejection by amending to remove “preventing” from the claim.
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.
Claims 2, 5, 6 and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Fernandes (Nature. 2020;586(7831):779-784).
Fernandes teaches dual inhibition of CD45 and PD1 using an anti-CD45 scFv fused to anti-PD1 scFv (RIPR-PD1; Fig 2b) within scope of antibody as defined in the instant specification (pg 13, lines 1-2). Fernandes teaches RIPR-PD1 potentiates (i.e. enhances) activation of antigen-stimulated T cells (i.e. TCR signaling) (Fig 3). Fernandes further teaches PIPR-PD1 reduces tumor progression in mouse models of SCLC and colon cancer (Fig 4).
Claims 2, 4-6, and 10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schlenker (Cancer Res. 2017;77(13):3577-3590).
Schlenker teaches engineering T cells to express a PD-1:28 receptor increases the effector functions of low-avidity T cells (T cells with intermediate- to low-affinity TCRs had better TCR-induced cytokine secretion) (i.e. engineered cells that enhance TCR signaling) (Abstract; Figure 2-3). Schlenker further observed these engineered T cells showed some benefits to intratumoral T-cell proliferation and tumor control in a melanoma xenograft mouse model (Figure 6), and observed these engineered T cells can synergize with anti-PD-L1 antibody treatment (Figure 5), suggesting the benefit of combination therapies in adoptive T-cell therapies (Abstract).
Claim Rejections - 35 USC § 103
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.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Fernandes as applied to claim 10 above, and further in view of Urbanek (J Med Chem. 2001;44(11):1777-1793).
Fernandes teaches claim 10 as discussed above.
However, Fernandes does not teach a CD45 inhibitor selected from the recited small molecule inhibitors 2-(4-acetylanilino)-3-chloronaphthoquinone, N-(9,10-dioxo-9,10-dihydrophenanthren-2-yl)-2,2-dimethylpropionamide, or analogs thereof.
Urbanek teaches a pivalamide compound 65 (identical to instant N-(9,10-dioxo-9,10-dihydrophenanthren-2-yl)-2,2-dimethylpropionamide; Table 1) as a potent CD45 inhibitor.
A skilled artisan would recognize that small molecule inhibitor, such as N-(9,10-dioxo-9,10-dihydrophenanthren-2-yl)-2,2-dimethylpropionamide as taught by Urbanek, can be used to inhibit CD45 as an alternative to a CD45 targeting scFv as taught by Fernandes with a reasonable expectation of success. Therefore, it would have been obvious to one of ordinary skill in the art prior to the effective filing date of the claimed invention that the CD45 scFv within a dual CD45-PD-1 targeted therapy as taught by Fernandez could be substituted by the small molecule CD45 inhibitor as taught by Urbanek as an alternative method for treating cancer.
Conclusion
No claims are currently allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HANNAH SUNSHINE whose telephone number is (571)270-7417. The examiner can normally be reached M-Th & Second Friday 8:30am-5pm EST.
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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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/HANNAH SUNSHINE/Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647