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/JP2021/021576, filing date 06/07/2021.
This PCT application claims priority to Japanese Application Nos. JP2021-063781
(filed 04/02/2021) and JP2020-099449 (filed 06/08/2020). 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 applications JP2021-063781 (filed 04/02/2021) and JP2020-099449 (filed 06/08/2020) 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 08/21/2023, is acknowledged. Claims 3-4, 8, 12, 19-20, 22-23, 25-27, and 32-43 are canceled. Claims 2, 5-7, 9-11, 13-15, 18, 21, and 24 are currently amended. Claims 1-2, 5-7, 9-11, 13-18, 21, 24, and 28-31 are currently pending and are examined on the merits herein.
Information Disclosure Statement
An information disclosure statement (IDS) was not submitted with the application.
Specification
The use of the terms BIAcore, KinexA, Biosystems, Merck, Millipore, Selleck, Tocris, Qiagen, BioLegend, R&D Systems, Santa Cruz Biotechnology, Thermo Fisher Scientific, Abcam, Cell Signaling Technology, GE Healthcare, LifeSpan BioSciences, Gene Tex, Corning, Bio-Rad, Essen Bioscience, Sigma-Aldrich, Roche, FlowJo, TreeView, Wako, CellSens, Olympus, Lab-Tek, Carl Zeiss, Cayman Chemical, Nikon, TaKaRa, Applied Biosystems, Microsoft, HyClone, Jackson, HiTrap, MabSelect Sure, Bethyl, GraphPad Prism, and Toray, 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.
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 drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Figures 46 and 48-55 contain sequences with no associated SEQ ID NOs.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, 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(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 1-2, 5-7, 9-11, 15-16, 21, and 24 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 claims 1-2, 5-7, 9-11, 15-16, 21, and 24: Claims 2, 5-7, 9-11, 15-16, 21, and 24 are dependent on claim 1, and claim 1 is inclusive of a large genus of “a drug” that is recited to reverse resistance to the anticancer drug in a cancer.
A written description requirement issue generally involves the question of whether the subject matter of a claim is supported by [conforms to] the disclosure of an application as filed (see MPEP 2163.01). Further, the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species. A "representative number of species" means that the species which are adequately described are representative of the entire 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 (see MPEP 2163.05).
The term “drug” in instant claim 1 (and, thus, instant claims 2, 5-7, 9-11, 15-16, 21, and 24) is broad and only limited by the functional description of having the ability to reverse resistance to an anticancer drug due to IL-26 in a cancer. Applicant disclosure provides: “…the “drug that reverses the resistance of IL-26 to the anticancer drug” means a drug that can enhance the sensitivity of cancer cells to the anticancer drug by weakening or losing the resistance to the anticancer drug acquired by the cancer cells due to IL-26. Typically it is an IL-26 inhibitor. Examples… include… IL-26 dsRNA or shRNA, IL-26 antisense, anti-IL-26 antibodies, aptamers against IL-26…anti-EphA3 antibody” (p.44, [0039]). Applicant disclosure provides support for the following structures and functions related to the “drug”:
The disclosure fully supports structures for the monoclonal IL-26 antibodies “69-10” and “31-4” which are shown to reduce proliferation in TNBC and reversing resistance to the anticancer drug gefitinib (Figs.5D and 11).
The disclosure provides data supporting that soluble EphA3 also functionally exhibits the ability to inhibit the interaction between EphA3 and IL-26 and thus reduce proliferation (Fig.19). The prior art provides the amino acid sequence/structure for EphA3 (see p.9 of UniProt. P29320— EPHA3_HUMAN, 2006-10-17, p.1-11).
The disclosure provides data supporting that monoclonal IL-26 antibodies “2-2” and 20-3” also functionally exhibit the ability to reduce proliferation in TNBC cells (Figs.5D and 11); however, adequate structures for these “drugs” are not provided by the disclosure. The prior art also does not provide any structures for these monoclonal antibodies.
The disclosure supports that the (commercially-available) anti-IL-26 polyclonal antibody (R&D Systems) also exhibits the function of reducing proliferation in TNBC and reversing resistance to the anticancer drug gefitinib (Fig.11). Claim Interpretation: The anti-IL-26 polyclonal antibody from R&D Systems is interpreted to mean the goat anti-human IL-26 polyclonal antibody (AF1375). This interpretation is based on applicant disclosure antibody list (p.66) and vendor information Human IL-26/AK155 Antibody. R&D Systems—Catalog#AF1375, polyclonal goat IgG.
The disclosure provides data supporting that 2 different EphA3 siRNAs exhibited the function of reducing proliferation in TNBC and reversing resistance to the anticancer drug gefitinib (Fig.23); however, structures for ”EphA3 siRNA-1” and “EphA3 siRNA-2” are not provided by the specification or the sequence listing.
The disclosure provides data supporting that a commercially-available anti-EphA3 polyclonal antibody (R&D Systems) was also exhibits the function of reducing proliferation in TNBC and reversing resistance to the anticancer drug gefitinib (Fig.16), as well as reducing expressing/colocalization of IL-26 with EphA3 (Fig.20). Claim Interpretation: The anti-EphA3 polyclonal antibody from R&D Systems is interpreted to mean the goat anti-mouse EphA3 polyclonal antibody (AF640). This interpretation is based on applicant disclosure antibody list (p.66) and vendor information Mouse EphA3 Antibody. R&D Systems—Catalog#AF640, polyclonal goat IgG.
The disclosure does not otherwise provide any evidence for IL-26 dsRNA, IL-26 shRNA, IL-27 siRNA, IL-26 antisense, IL-26 aptamers, or any other IL-26 inhibitor that fits within the genus of “a drug” as is broadly claimed.
The state of the prior art at the time of the instant application teaches that even the sub-group of IL-26 inhibitors included in the genus of the claimed “drug” is broad and varied; and, that the full scope of IL-26 inhibitors included in the genus of the claimed “drug” not supported by applicant disclosure. Gilliet, et al.—US20180207271A1. IL-26 inhibitors (herein referred to as Gilliet) teaches IL-26 specific siRNA, IL-26 specific antisense oligonucleotides, IL-26 specific ribozymes oligonucleotide, IL-26 specific zinc finer nuclease oligonucleotide, dominant negative IL-26, and IL-26 aptamers for treating diseases caused by or associated with IL-26 (title; abstract; p.2, [0026]). Regarding written description for product claims 1-2, 5-7, 9-11, 15-16, 21, and 24: A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or by describing structural features common to that genus that “constitute a substantial portion of the genus.” See University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997): “A description of a genus of cDNAs may be achieved by means of a recitation of a representative number of cDNA, defined by nucleotide sequence, falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus.”
In regards to claims to a product defined by function, without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 at1568 USPQ2d at 1406 (“definition by function…does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).Because the disclosure and prior art fail to describe common attributes or characteristics that adequately identify members of the genus of “a drug,” the disclosure of the commercially available anti-IL-26 and anti-EphA3 polyclonal antibodies and the “69-10” and “31-4” IL-26 monoclonal antibodies, and the soluble EphA3 protein discussed above is insufficient to describe the genus. Thus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus as broadly claimed.
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).
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 1-2, 7, 9-11, 15, 21, and 24 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Hor, et al. The T-cell lymphokine interleukin-26 targets epithelial cells through the interleukin-20 receptor 1 and interleukin-10 receptor 2 chains. JBC (2004), 279:32, p.33343-33351 (herein referred to as Hor); and, as evidenced by Ling, et al. Abstract 1008: Characterizing the post-translational regulation of programmed death-ligand 1 (PD-L1) in triple-negative breast cancer: Role of EphA3/Fes/Fer. Cancer Research (2020), p.1-5 (herein referred to as Ling), Nedeljkovic and Damjanovic. Mechanisms of chemotherapy resistance in triple-negative breast cancer—How we can rise to the challenge. Cells (2019), 8:957, p.1-32 (herein referred to as Nedeljkovic), Trotter, et al. IL26, a noncanonical mediator of DNA inflammatory stimulation, promotes TNBC engraftment and progression in association with neutrophils. Cancer Research (May 2020), p.1-7 (herein referred to as Trotter), and Guerrab, et al. Co-targeting EGFR and mTOR with gefitinib and everolimus in triple-negative breast cancer cells. Scientific Reports (April 2020), 10:6367, p1-12 (herein referred to as Guerrab).
Hor teaches treatment of colon carcinoma cells (i.e., Col-205, Lovo, and SW-403 cells) and keratinocytes (i.e., HaCaT cells) with a composition wherein the active agent is a goat anti-human IL-26 polyclonal antibody which is a commercial antibody provided by R&D Systems (i.e., AF1375; title; p.33344, col.2, para.4; p.33349, col.2, para.1). And, applicant disclosure recites the use of this IL-26 pAb composition in reducing proliferation and reversing resistance in TNBC cells where the cancer is due to IL-26 and which has low sensitivity to the anticancer drug gefitinib. That is, instant Fig.11 shows reversal of resistance to anticancer drug gefitinib with the anti-IL-26 pAb; and, gefitinib is a tyrosine kinase inhibitor, as evidenced by Guerrab (abstract).
The determination of whether a preamble limits a claim is made on a case-by-case basis and claims reciting a purpose or intended use are considered to limit a claim when the purpose or intended use results in a structural difference between the claimed invention and the prior art (see MPEP 2111.02). In the case of claim 1, the intended use/purpose of the claimed “pharmaceutical composition comprising, as an active ingredient, a drug that reverses resistance to the anticancer drug due to IL-26 in a cancer” is “for use in combination with an anticancer drug.” The recited purpose/intended use does not result in a structural difference in the pharmaceutical composition comprising the drug. As this “drug” taught by Hor has the same structure as that of applicant’s which also comprises the R&D Systems goat anti-human IL-26 polyclonal antibody/pAb, the drug would be capable of performing the recited function in claim 1 of reversing resistance to the anticancer drug due to IL-26 in a cancer as evidenced by applicant specification (see p.66 antibody list; Fig.11; p.75, [0117]).
Instant claim 2 recites that the cancer is breast cancer that is HER2 negative or that is TNBC; however, these terms are further descriptions of the intended use and do not structurally change the drug/composition taught by Hor. Instant claim 5 recites that the cancer is a cancer expressing EphA3, which includes TNBC as evidenced by Ling (abstract); however, these terms are further descriptions of the intended use and do not structurally change the drug/composition taught by Hor. Instant claim 6 recites that the cancer is a cancer having low sensitivity to the anticancer drug or exhibits resistance to the anticancer drug, which includes TNBC as evidenced by Nedeljkovic (title, abstract); however, these terms are further descriptions of the intended use and do not structurally change the drug/composition taught by Hor. Instant claim 7 recites that the low sensitivity or resistance is caused by IL-26 or phosphorylation of AKT and/or JNK due to IL-26; however, these terms are further descriptions of the intended use and do not structurally change the drug/composition taught by Hor. Instant claim 9 recites that the IL-26 is produced by CD4+ T cells, which is evidenced by Trotter (abstract); however, these terms are further descriptions of the intended use and do not structurally change the drug/composition taught by Hor. Instant claim 10 recites that the anticancer drug is a tyrosine kinase inhibitor (TKI) and instant claim 11 recites that the TKI is an epidermal growth factor receptor (EGFR) TKI that is gefitinib, which is evidenced by Guerrab (title; abstract); however, these terms are further descriptions of the intended use and do not structurally change the drug/composition taught by Hor. Instant claim 15 recites that the drug of the composition is an anti-IL-26 antibody, which is taught by Hor above. Claim 21 recites that the composition comprising the drug is a proliferation inhibitor for cancer cells that have low sensitivity or that exhibit resistance, which does not structurally change the drug/composition taught by Hor. Claim 24 recites that the composition is administered simultaneously with the anticancer drug, after administration of the anticancer drug, or before administration of the anticancer drug. These descriptions also further describe the intended use of the composition in combination with an anticancer drug and do not change the drug/composition taught by Hor.
Allowable Subject Matter
Claims 28-31 are allowed.
Claims 13-14 and 17-18 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
Regarding allowable claims 28-31
The method of improving responsiveness to an anticancer drug and the method for treating cancer in cancer patients having a low sensitivity to an anticancer drug or exhibiting resistance to the anticancer drug by inhibiting IL-26 is novel. Further, the methods wherein inhibiting IL-26 decreases the interaction between IL-26 and EphA3 is also novel. Gilliet teaches IL-26 inhibitors for treatment of inflammatory diseases but does not make mention of methods of inhibiting IL-26 in cancer.
Additional allowable subject matter:
Additionally, the concept of therapeutic targeting of IL-26 mediated resistance to TNBC by inhibiting proliferation specifically with IL-26 monoclonal antibodies encoded by VH SEQ ID NO: 2 and VL SEQ ID NO: 4 (i.e., antibody “31-4”) and VH SEQ ID NO: 4 and VL SEQ ID NO: 14 (i.e., antibody “60-10”); and, by inhibiting the interaction between IL-26 and EphA3 using the anti-EphA3 antibody and soluble EphA3 protein is novel.
Closest prior art to allowable subject matter:
Pasquale. Eph receptors and ephrins in cancer: bidirectional signalling and beyond. Nature Reviews (2010), 10, p.165-180 (herein referred to as Pasquale) teaches the relationship between Eph receptor dysregulation and cancer (title; Table 1; Fig.4). However, Pasquale does not teach the interaction between EphA3 and IL-26 nor specifically reference the interaction in TNBC.
Vail, et al. Targeting EphA3 inhibits cancer growth by disrupting the tumor stromal microenvironment. Therapeutics, Targets, and Chemical Biology (2014), 74:16, p.4470-4481 (herein referred to as Vail) teaches the relationship between EphA3 overexpression and cancer (title; abstract). However, Vail does not teach the interaction between EphA3 and IL-26 nor specifically reference the interaction in TNBC.
Ling teaches the relationship between EphA3 and TNBC specifically (title). However, Ling does not teach the interaction between EphA3 and IL-26.
The prior art also teaches the R&D Systems goat anti-mouse polyclonal anti-EphA3 antibody (as well as other anti-EphA3 antibodies). However, these antibodies are only cited for biochemical assays and not compositions. For example, see p.3 para.3 of Rosas, et al. Expression and activation of Ephexin is altered after spinal cord injury. Developmental Neurobiology (2011), 71:7, p.1-20 and p.8093 col.2 para.4 of Vaidya, et al. EphA3 null mutants do not demonstrate motor axon guidance defects. Molecular and Cellular Biology (2003), 23:22, p.8092-8098. The prior art does not teach pharmaceutical compositions comprising soluble EphA3.
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