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
Note that claims 10-11 and 17, drawn to a non-elected invention, are withdrawn but still pending.
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). The table of [00181] of the clean substitute specification filed 1/9/2026 does not have sequence identifiers (SEQ ID NO:) for the final sequence (i.e., wherein there are no “X” designated amino acids) of the VH for huB1H2-V2, -V8, -V14, -V20, for huB1H2-V3, -V9, -V15, -V21, for huB1H2-V5, -V11, -V17, -V23, for huB1H2-V6, -V12, -V18, -V24, and of the VL for huB1H2-V1, -V6, for huB1H2-V7, -V12, for huB1H2-V13, -V18, and for huB1H2-V19, -V24.
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.
Specification
The disclosure is objected to because of the following informalities: The size of the text file is required to be in bytes instead of KB or kilobytes (see 37 CFR 1.52(e)(5), see 37 CFR 1.823(b)(1)). The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) and added by the amendment filed 1/9/2026 recites the file size in KB instead of bytes.
Appropriate correction is required.
Claim Objections
Claim 6 is objected to because of the following informalities: As amended, claim 6 recites after (a) “binds bind”, after (b) “blocks block” and after (c) “induces induce”.
Appropriate correction is required.
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 2 and 3 remain 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.
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, claims 2 and 3 recite the broad recitation “at least 95%” sequence identity, and the claims also recite “96%, 97%, 98%, 99% or 100%” 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. If a sequence has 100% identity to another sequence, then it necessarily has at least 95%, 96%, 97%, 98%, 99% identity. Therefore, as discussed above, the claims are indefinite.
Applicant argues (section IV. of REMARKS) claims 2 and 3 have been amended to recite “…sequence having at least 95% sequence identity to SEQ ID NOs:…” Further, the different percent identities are separated by the term “or” to recite a finite list of alternatives, signaling a clear Markush group, which may contain “the double inclusion of an element by members of a Markush group…” The inclusion of both 100% and 95% is merely redundant not indefinite. The metes and bounds are precise. “There is no “question or doubt” (as posited by the Examiner) regarding whether the features are required--the claim requires the sequence identity to meet at least one of the recited alternatives.” (emphasis by Applicant) There is no prima facie case that the invention as claimed in claims 2 and 3 are indefinite. The argument has been fully considered but is not persuasive. First, the claims have been amended but still recite the range of alternative percent identities: “having at least 95%, 96%, 97%, 98%, 99% or 100% [sequence] identity”. Applicant’s reference to double inclusion in the MPEP 2173.05(h) is not persuasive. The question is whether the recitation of the range of sequence identities makes the claims indefinite. It is maintained for the reasons of record that in this situation it does 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. Again, if the sequence is 100% identical, then it is at least 95% identical; however, the opposite is not true. This is different than the Markush example provided in the MPEP 2173.05(h) (the section cited by Applicant) referring to double inclusions and, in particular, MPEP 2173.05(o): Double Inclusions. In section 2173/05(o) an example is given of inclusion of a “chloro” and a “halogen”, which is generic to a “chloro” and is a subtype of chemical that is encompassed by the inclusive broader family of chemicals. However, the instant claims recite overlapping ranges. Recitation of the different percent identities in the alternative does not remove the indefiniteness. If Applicant intends that sequences at least 95% are included, then only a single percent identity needs to be identified. As exemplified in MPEP 2173.05(c)(I): Numerical Ranges and Amounts in Limitations:
While a single claim that includes both a broad and a narrower range may be indefinite, it is not improper under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C.112, second paragraph, to present a dependent claim that sets forth a narrower range for an element than the range set forth in the claim from which it depends. For example, if claim 1 reads "A circuit … wherein the resistance is 70-150 ohms." and claim 2 reads "The circuit of claim 1 wherein the resistance is 70-100 ohms.", then claim 2 should not be rejected as indefinite.
Therefore, it is suggested that if Applicant intends that the sequence identity percentage may be narrower, then an independent claim(s) drawn to the narrower percentage be added. Otherwise, it is maintained for the reasons of record that the claims remain 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.” Note claims that depend from claims 2 and 3 were not rejected.
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.
Claim 7 remains 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.
Claim 7 depends from claim 1 and is drawn to the monoclonal antibody or antigen-binding portion thereof that binds BCMA. Claim 1 limits the heavy and light chain CDRs of the antibody or antigen-binding fragment thereof to specific CDRs which were obtained from a monoclonal antibody, B1H2, produced by immunization of a mouse ([00139]-[00141]). Based on the B1H2 CDRs, a number of humanized versions were produced (Table 3). As a result, while the specification discloses a mouse and humanized antibodies meeting the limitations of claim 7, and one skilled in the art could readily envision antigen-binding fragments thereof, as well as a chimeric antibody, this is not the case for a human antibody.
An antibody that originates in a mouse cannot be a “human” antibody unless the mouse has a human Ig repertoire, which there is no evidence the immunized mouse of Example 1 did. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention. For antibodies, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural "stepping stone" to the corresponding chimeric antibody, but not to human antibodies. Centocor Ortho Biotech, Inc. v. Abbott Laboratories, 636 F.3d 1341, 97 USPQ2d 1870 at 1875 (Fed. Cir. 2011) set forth that, (“[T]he application only provides amino acid sequence information (a molecular description of the antibody) for a single mouse variable region, i.e., the variable region that the mouse A2 antibody and the chimeric antibody have in common. However, the mouse variable region sequence does not serve as a stepping stone to identifying a human variable region within the scope of the claims.”). A chimeric antibody shares the full heavy and light chain variable regions with the corresponding mouse antibody; that is, the structure shared between a mouse and chimeric antibody would generally be expected to conserve the antigen binding activity. A humanized antibody shares the same CDRs with a mouse antibody but has altered framework regions to resemble human sequences (see also [0047]).
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 the isolated monoclonal antibody, or antigen-binding fragment thereof, of claim 1 which is a mouse, chimeric or humanized antibody, 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).
Applicant argues in section III. that claim 7 has been amended to recite:
7. The isolated monoclonal antibody, or the antigen-binding portion thereof, of claim 1, which is a mouse, chimeric or humanized antibody or antigen-binding portion thereof.
Examples 1-2 and Table 3 of the specification clearly describe mouse, chimeric and humanized antibodies. The argument has been fully considered but is not persuasive. Claim 7 has not been amended to remover reference to a human antibody. Further, even though the claim has been amended to add “or antigen-binding portion thereof”, for the reasons of record there is no support for written description of an antigen-binding portion of a human antibody. The skilled artisan would not reasonably expect an antigen-binding portion of the disclosed mouse antibody to be the same as an antigen-binding portion of a human antibody. As discussed in the rejection, disclosure of a mouse antibody does not allow the skilled artisan to immediately envisage a human antibody (or antigen-binding portion thereof). [See Centocor Ortho Biotech, Inc. v. Abbott Laboratories, 636 F.3d 1341, 97 USPQ2d 1870 at 1875 (Fed. Cir. 2011) discussed in the rejection.]
New
Claim 6 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 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.
Claim 6 has been amended to recite that the antibody or antigen-binding portion thereof “is able to … induce antibody dependent cell mediated cytotoxicity against BCMA expressing cells." However, the claim does not specify under what conditions the antibody or antigen-binding portion “is able to” induce antibody-dependent cell-mediated cytotoxicity (ADCC) or further limit the encompassed antibodies to those with the ability to induce ADCC. The specification discloses only one chimeric and two humanized versions of anti-BCMA antibody B1H2 (chimeric B1H2 and huB1H2-V10 and -V33) that were shown to induce ADCC in vitro (see Figs.10A and 10B, [00171] and [00177]). These antibodies comprise not only a BCMA-binding portion, but also an Fc region. They are considered full-length antibodies produced or modified from a mouse monoclonal antibody. No antibody-binding portion in a context of other than as part of a full antibody induced ADCC. This is supported by Googlish et al. (Int. J. Mol. Sci. 22, 8947, 25 pages, 2021) which discuss that one function of FcγRs is to induce ADCC, which occurs through binding of an antibody Fc region to the FcγRIIIa on the target cell (e.g., Fig. 2). “ADCC and ADCP are two mechanisms mediated by direct interaction of the antibody’s Fc domain with the corresponding FcγR.” (p. 5/25, second paragraph). Monoclonal antibodies or antigen-binding portions thereof of claim 1 which bind BCMA and which comprise an FcγRIIIa-binding Fc region meet the written description provision of 35 USC 112(a). However, the claims are directed to or encompass antigen-binding fragments of the monoclonal antibody that merely are “capable of binding” to BCMA and comprise a heavy chain variable region (VH) and light chain variable region (VL) as set forth in claim 1, without the requirement of having an FcγRIIIa-binding Fc region. None of these sequences 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).
With the exception of the monoclonal antibody of claim 1 or antigen-binding fragment thereof which binds BCMA and comprises an Fc region that binds to FcγRIIIa as discussed above (e.g., as in claim 5), the skilled artisan cannot envision the detailed chemical structure of the encompassed antigen-binding portions that are capable of inducing ADCC, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The product itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016 (Fed. Cir. 1991).
Therefore, only a BCMA-binding monoclonal antibody of claim 1 or an antigen-binding portion thereof comprising an Fc region that binds to FcγRIIIa, 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).
Allowable Subject Matter
Claims 1, 8, 9, 12-16 and 18-20 remain allowed, except as objected to above.
Claims 2 and 3 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.
Claims 4 and 5 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.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa Ford, can be reached at (571) 272-0857.
Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
Official papers filed by fax should be directed to (571) 273-8300. NOTE: If applicant does submit a paper by fax, the original signed copy should be retained by the applicant or applicant's representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED so as to avoid the processing of duplicate papers in the Office.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice .
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
Claire Kaufman
/Claire Kaufman/
Primary Examiner, Art Unit 1674
March 24, 2026