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 .
Election/Restrictions
Applicant’s election of Group I in the reply filed on 02/04/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
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:
A) Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
The sequence disclosures are located on p. 64, line 14, and p. 65, line 16 (clean substitute specification filed 11/10/2023).
B) 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). (See preceding paragraph)
Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, 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;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
Information Disclosure Statement
It is noted that US 20100155133 A1 (Makwinski), cited on the IDS filed 2/5/2026, is drawn to “DOWNWARD FACING RECEPTACLE ASSEMBLY FOR CABLE RACEWAY“. US Patent 5,073,972 (Kwon) is drawn to “Precharge System For A Semiconductor Memory Device”.
In the IDS filed 2/5/2026, reference #13, REMINGTON,..(1995), is merely a citation by another article. There is no part of the reference disclosed other than title and date. As a result, it has been lined-through on the IDS.
Specification
The use of the term Abzena (p. 66, line 23, and p. 68, line 4) and Fortebio (p. 68, line 26, and p. 71, line 19) which is a trade name or a mark used in commerce, has been noted in this application. The 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.
Applicant is encouraged to review the specification for other company names which are trademarked.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 13, 26, 30 and 68 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 13 and 26, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 30 recites the broad recitation of at least 80%, and the claim also recites at least 99% amino acid sequence identity, which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. A sequence which is at least 99% identical will also be at least 80%, 90%, 95% and 97% identical.
Similarly for claim 68, a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 68 recites the broad recitation “sarcoma”, and the claim also recites “fibrosarcoma, … leimysoarcoma, rhabdomysocaroma, liposarcoma”, which are the narrower statements of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
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 46, 50 and 51 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.
Claims 46, 50 and 51 recite that the antibody comprises a first and second heavy chain and specifies amino acid substitutions therein. The position is described in the claims as, for example, “corresponding to K 409 in a human IgG1 heavy chain ,… wherein the amino acid position in the constant regions are numbered according to EU numbering.” However, the specification on p. 9, lines 16-20, defines “immunoglobulin heavy chain” as “typically comprised of a heavy chain variable region (...VH) and a heavy chain constant region (…HC) which defines the isotype of the immunoglobulin. The heavy chain constant region typically is comprised of three domains, CH1, CH2, and CH3.” First, this does not require that the antibody of the claims comprise a full immunoglobulin HC, more particularly an Fc region. The definition merely refers to typical HCs and is non-limiting. As a result, when the claim provides a particular position at which an amino acid substitution is made, e.g., wherein the position is found in human IgG1 HC, this presumes the claimed antibody has a HC Fc region, which is not required by the claims. Second, neither the specification nor the prior art supports mutations at the recited Fc positions in any immunoglobulin other than IgG1-4 isotypes (see, e.g., Brinkmann et al. (MABS, 9(2):182–212, 2019, Section “Bispecific IgGs with an asymmetric Fc region - solving the heavy chain problem”, beginning p. 189, col. 1, second paragraph). Further, as described by Brinkmann et al. (ibid., p. 188, col. 2, third paragraph), unlike in IgGs, the CH2 domain of IgM and IgE act as hinge regions connecting a Fab arm to Fc region formed by CH3 and CH4. Although, there are also significant differences between IgGs and IgA and IgD immunoglobulins also. The specification does not support the recited HC substitutions in any immunoglobulins other than IgG isotypes. However, the claims are directed to or encompass antibody with heavy chains encompassing substitutions of L234, L235, D265 and/or K409 and F405 wherein the HCs do not comprise full Fc regions and/or are not one of IgG1, IgG2, IgG3 or IgG4. None of these heavy chains or constant regions thereof meets the written description provision of 35 USC 112(a).
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111 (Fed. Cir. 1991), clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
Therefore, only wherein the antibody comprises an IgG1, IgG2, IgG3 or IgG4 heavy chain Fc region in which the substitution is present as described in the claims, including wherein the amino acid positions in the constant regions are numbered according to EU numbering, but not the full breadth of the claim meets the written description provision of 35 U.S.C. § 112(a). Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. § 112 is severable from its enablement provision (see page 1115).
Claims 62 and 66-68 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 a method of treating ROR2-expressing cancers by administration of a bispecific antibody having the ROR2-binding antigen-binding region of claim 1 and a CD3-binding region, does not reasonably provide enablement for wherein the cancers do not express ROR2. 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.
The claims lack enablement for two reasons. The first deals with expression of ROR2 on the cancer to be treated. The second with what type of antibody can be used for the treatment.
According to the specification on p. 1, lines 1-4, “ROR2 expression is found on human tumor cells in numerous cancer tissues, including sarcoma, uterine, pancreas, melanoma, renal cell carcinoma, prostate carcinoma, colorectal cancer, squamous cell carcinomas of the head and neck, stromal tumors and breast cancer tissue (reviewed in Debebe and Rathmell 2015, Pharmcol & Therap 150:143-148).” Also, Goydel et al. (J. Biol. Chem. 295(18):5995-6006, 2020, cited in the IDS filed 11/6/2023) showed that a humanized antibody specific for human ROR2 converted to a bispecific T cell-engaging ROR2xCD3 antibody caused in vitro cytokine release in the presence to ROR2 target cells (Fig. 5C) and lysed ROR2-expressing target cells in the presence of expanded primary T cells (Fig. 5B). This was not the case with cells expressing ROR1 but not ROR2 (paragraph bridging pp. 5999-6001). Instant Figures 5A, 5B and 6 show that activity of the claimed bispecific ROR2 x CD3 antibody correlates with the amount of ROR2 expression on the target cell. If the target cell, i.e., the cancer cell, does not express ROR2, the antibody will not bind it and bring the T cell into proximity to induce target cell lysis. Therefore, one skilled in the art cannot used the invention to treat a cancer that does not express ROR2. (See also p. 42, lines 5-16.)
Claim 1, upon which claims 62 and 66-68 ultimately depend, is drawn to an antibody binding ROR2 and having heavy and light chain variable regions with specified CDR1-3. No anti-cancer activity has been shown for a monospecific antibody with an antigen-binding site which binds ROR2 and has these CDRs but without more. What the antibody used in the method, i.e., the antibody of claim 1, does not have is the ability alone to kill cancer cells. As disclosed in the specification and prior art, more is required for that ability--either addition of a conjugated drug (e.g., ClinicalTrials.gov study NCT 03504488, v.7, “CAB-ROR2-ADC Safety and Efficacy Study in Patients with Solid Tumors”, 04/30/2019, https://clinicaltrials.gov/study/NCT03504488?term=NCT03504488&viewType=Table&rank=1&tab=history&a=7#version-content-panel) or inclusion of a CD3-binding site to bring T cells into proximity for target cell killing as discussed above (see also Sharp et al., Canc. Res. 78(13):833, 2018, cited in the IDS filed 11/06/2023). All the working examples of the instant application directed toward cancer cell inhibition or lysis use the ROR2 antibody in the form of a bispecific antibody that also comprises a CD3ε-binding site (see also instant claim 26, 28, 30, 38, 41-43, 53). As a result, it would require undue experimentation for the skilled artisan to practice the method of treatment commensurate in scope with the claims.
Prior Art
The prior art made of record and not relied upon is considered pertinent to Applicant's disclosure.
US 20200123255, cited in the IDS filed 11/6/2023, and continuations and/or divisionals thereof, and WO 2015/001085, cited in the IDS filed 2/5/2026, teach antibody IgG1-huCD3-H1L1, used in the production of the instant CD3 x ROR2 bispecific antibody (instant specification p. 70, lines 10-15).
WO 2017/009442, cited in the IDS filed 2/5/2026, teaches antibody variant IgG1-huCD3-H1L1-H101G (instant specification p. 71, lines 7-13).
Many of the US pregrant publications and patents cited in the IDS filed 11/6/2023 teach IgG Fc region mutations L234F, L235E, D265A, and/or K409R, F405L, such as US 2020199229 A1 and US Patents 10,590,206 B2 and 10,344,050 B2. See also, for example, Gramer et al. (mAbs, 5(6):962-973, 2013, cited in the IDS filed 2/5/2026).
Allowable Subject Matter
Claims 1, 3, 4, 6, 7, 11, 25, 28, 38-43, 47, 53, 58 and 80 are allowed.
Claims 13, 26 and 30 would be allowable if rewritten to overcome the rejection(s) under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), 2nd paragraph, set forth in this Office action and to include all of the limitations of the base claim and any intervening claims.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Claire Kaufman, whose telephone number is (571) 272-0873. Examiner Kaufman can generally be reached Monday through Friday 7am-3:30pm, Eastern Time.
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Claire Kaufman
/Claire Kaufman/
Primary Examiner, Art Unit 1674
May 29, 2026
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