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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 16 March 2026 has been entered.
Status of Application, Amendments and/or Claims
The amendment and Applicant’s arguments, filed 16 March 2026 have been entered in full. Claims 1-3, 5, 12-15, 17-19 are withdrawn from consideration as being drawn to a non-elected invention. Claims 4, 7, 9, 10, 16, 21, 22 and 25 are canceled. Claims 6, 20, 23 and 24 are amended. New claims 26-30 are added.
Claims 6, 8, 11, 20, 23, 24, 26-30 are under examination.
Withdrawn Objections And/Or Rejections
The objection to the disclosure because of embedded hyperlinks and/or other form of browser-executables codes, as set forth at pages 3-4 of the previous Office Action (15 October 2025), is withdrawn in view of the amendment (16 March 2026).
The rejection to claims 6, 8-11, 20, 22-25 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, written description, as set forth at pages 4-9 of the previous Office Action (15 October 2025), is withdrawn in view of the amendment (16 March 2026).
The rejection to claims 6, 8-11, 20, 22-25 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as set forth at pages 9-11 of the previous Office Action (15 October 2025), is withdrawn in view of the amendment (16 March 2026).
The rejection to claims 6, 8-11, 20, 22-25 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, written description, new matter, as set forth at pages 12-13 of the previous Office Action (15 October 2025), is withdrawn in view of the amendment (16 March 2026).
The rejection to claims 6, 9-11, 20, 22-25 under 35 U.S.C. 103 as being unpatentable over Lohse et al. (Characterization of a mutated IgA2 antibody of the m(1) allotype against the epidermal growth factor receptor for the recruitment of monocytes and macrophages, The Journal of Biological Chemistry Volume 287/Number 30:25139-25150, 2012) in view of Frazier et al. (US 2015/0274826; published 01 October 2015), as set forth at pages 13-16 of the previous Office Action (15 October 2025), is withdrawn in view of the amendment, which recites, “..wherein said first binding moiety is an IgA2 antibody with at least two mutations in a constant region of the IgA2 antibody, wherein the at least two mutations are selected from the group consisting of N45.2G, P124R, C92S, N120T, I121L, T122S, deletion of C147 and deletion of Y148 relative to SEQ ID No: 3, numbering according to IMGT scheme..” (16 March 2026).
The rejection to claims 6, 8-10, 20, 22-25 under 35 U.S.C. 103 as being unpatentable over Lohse et al. (The Journal of Biological Chemistry Volume 287/Number 30:25139-25150, 2012) in view of Pons et al. (ALEXO THERAPEUTICS, INC WO 2018/057669; published 29 March 2018), as set forth at pages 16-19 of the previous Office Action (15 October 2025), is withdrawn in view of the amendment, which recites, “..wherein said first binding moiety is an IgA2 antibody with at least two mutations in a constant region of the IgA2 antibody, wherein the at least two mutations are selected from the group consisting of N45.2G, P124R, C92S, N120T, I121L, T122S, deletion of C147 and deletion of Y148 relative to SEQ ID No: 3, numbering according to IMGT scheme..” (16 March 2026).
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 instant specification remains objected to because it fails to meet the requirement for Patent Applications containing nucleotide and/or amino acid sequence disclosures.
The substitute specification (submitted 16 March 2026) recites a sequence, which lacks a SEQ ID NO: (see New claim 29). The substitute specification recite sequences (see page 16, line 22 and page 21, line 13).
The Examiner notes that the entire specification should be for sequences that lack SEQ ID Nos: in accordance with the requirements of 37 CFR 1.821-1.825.
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.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
A. Claims 6, 8, 11, 20, 23, 24 (and new claim 27) remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 12,258,420 in view of Lohse et al. (The Journal of Biological Chemistry Volume 287/Number 30:25139-25150, 2012), Frazier et al. (US 2015/0274826; published 01 October 2015) and Pons et al. (WO 2018/057669; published 29 March 2018).
The basis for this rejection is set forth in the previous Office Action (15 October 2025, pages 19-24).
APPLICANT’S ARGUMENTS: Applicant argues that without conceding to the validity of this rejection and solely to expedite prosecution, Claim 6 has been amended to recite that the second binding moiety enhances neutrophil-mediated cytotoxicity of the first binding moiety on the tumor relative to the composition that lacks the second binding moiety. Applicant argues that the '420 patent is directed to a pharmaceutical composition comprising an engineered IgA2 antibody or functional fragment thereof, wherein the IgA2 Ch3 region comprises a mutation. Applicant argues that Lohse fails to teach or suggest that the second binding moiety enhances neutrophil-mediated cytotoxicity of the first binding moiety on the tumor relative to the composition that lacks the second binding moiety. Applicant argues that the combination of '420 and Lohse fails to teach or suggest all the elements of amended Claim 6.
Applicant’s arguments have been fully considered but are not found persuasive for the following reasons:
1. Amended Claim 6 recites that the first binding moiety is an IgA2 antibody with at least two mutations in a constant region of the IgA2 antibody wherein the at least 2 mutations are selected from the group consisting of N45.2G, P124R, C92S, N120T, I121L, T122S, deletion of C147 and deletion of Y148 relative to SEQ ID NO:3 numbering according to IMGT scheme, wherein the first binding moiety specifically binds CD89 and an extracellular membrane bound tumor antigen or an extracellular membrane bound Treg antigen. New claim 27 recites that the antibody further comprises N135Q mutation.
The '420 patent teaches a pharmaceutical composition comprising an IgA2 antibody or functional fragment thereof, wherein constant region in the IgA2 antibody comprises mutations including deletion of C147, deletion of Y148, N45.2G and N135Q.
The claims of the ‘420 patent do not teach that an IgA2 antibody can bind CD89 and an extracellular membrane-bound tumor antigen on cells in a tumor.
However, Lohse et al. teach IgA antibodies have two IgA isotypes (IgA1 and IgA2). Lohse et al. teach IgA antibodies can bind CD89. Lohse et al. teach IgA2 antibodies made against epidermal growth factor receptor (EGFR) with a P221R-mutation IgA2m(1). Lohse et al. teach that the mutation is a point mutation from proline to arginine at position 221 in the constant domain of the IgA2 antibody. Lohse et al. teach that the epidermal growth factor receptor (EGFR) constitutes a well-established target molecule for tumor therapy. Lohse et al. teach the EGFR antibodies have dual modes of action against cancer cells. The fragment crystallizable (Fc) part can trigger effector mechanisms such as complement-dependent cytotoxicity, phagocytosis, or ADCC.
2. Amended Claim 6 recites that the structure of the second binding moiety is an antibody that specifically binds CD47 and blocks CD47 mediated signaling of SIRPa.
The claims of the ‘420 patent do not teach a second binding moiety that specifically binds CD47 and blocks CD47 mediated signaling of SIRPa.
However, Frazier et al. teach an anti-CD47 antibody that specifically binds CD47 and blocks CD47 mediated signaling of SIRPa.
Chemical compounds and their properties are inseparable (In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA1963)), as are their processes and yields (In re Von Schickh, 362 F.2d 821, 150 USPQ 300 (CCPA 1966))..
The chemical structure of the anti-CD47 antibody of Frazier is the same structure that is recited in the instant claims. Therefore, this antibody would also have the associated function of “enhancing neutrophil-mediated cytotoxicity of the first binding moiety on the tumor relative to the composition that lacks the second binding moiety”
The scientific reasoning and evidence as a whole indicates that the rejection should be maintained.
B. Claims 6, 8, 11, 20, 23, 24 (and new claim 27) remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 11,091,562 in view of Lohse et al. (The Journal of Biological Chemistry Volume 287/Number 30:25139-25150, 2012), Frazier et al. (US 2015/0274826; published 01 October 2015) and Pons et al. (WO 2018/057669; published 29 March 2018).
The basis for this rejection is set forth in the previous Office Action (15 October 2025, pages 24-27).
APPLICANT’S ARGUMENTS: Applicant argues that without conceding to the validity of this rejection and solely to expedite prosecution, Claim 6 has been amended to recite that the second binding moiety enhances neutrophil-mediated cytotoxicity of the first binding moiety on the tumor relative to the composition that lacks the second binding moiety. Applicant argues that the '562 patent is directed to an engineered antibody or functional fragment thereof comprising an antigen binding domain and IgA constant domain, wherein the IgA heavy chain constant domain comprises a mutation. Applicant argues that as explained above, the cited references, Lohse, Frazier and Pons, alone or in combination, fail to teach or suggest that the second binding moiety enhances neutrophil-mediated cytotoxicity of the first binding moiety on the tumor relative to the composition that lacks the second binding moiety. Applicant maintains that the combination of '562 and the cited references, Lohse, Frazier and Pons, fails to teach or suggest all the elements of amended claim 6.
Applicant’s arguments have been fully considered but are not found persuasive for the following reasons:
1. The '562 patent teaches a pharmaceutical composition comprising an IgA antibody or functional fragment thereof, wherein constant region in the IgA antibody comprises mutations including deletion of C147, deletion of Y148, P124R, N45.2G and N135Q.
2. The teachings of Lohse et al. and Frazier et al and described above. Contrary to the presented arguments, the combination of '562 and the cited references, Lohse, Frazier and Pons teach or suggest all of the elements of amended Claim 6.
The scientific reasoning and evidence as a whole indicates that the rejection should be maintained.
C. Claims 6, 8, 11, 20, 23 and 24 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,059,909 in view of Lohse et al. (The Journal of Biological Chemistry Volume 287/Number 30:25139-25150, 2012), Frazier et al. (US 2015/0274826; published 01 October 2015) and Pons et al. (WO 2018/057669; published 29 March 2018).
The basis for this rejection is set forth in the previous Office Action (15 October 2025, pages 27-30).
APPLICANT’S ARGUMENTS: Applicant states that without conceding to the validity of this rejection and solely to expedite prosecution, Claim 6 has been amended to recite that the second binding moiety enhances neutrophil-mediated cytotoxicity of the first binding moiety on the tumor relative to the composition that lacks the second binding moiety. Applicant argues that the '909 patent is directed to an engineered antibody or functional fragment thereof comprising an antigen binding domain and IgA constant domain, wherein the IgA heavy chain constant domain comprises a mutation. Applicant maintains that as explained above, the cited references, Lohse, Frazier and Pons, alone or in combination, fail to teach or suggest that the second binding moiety enhances neutrophil-mediated cytotoxicity of the first binding moiety on the tumor relative to the composition that lacks the second binding moiety. Applicant argues that the combination of '909 and the cited references, Lohse, Frazier and Pons, fails to teach or suggest all the elements of amended claim 6.
Applicant’s arguments have been fully considered but are not found persuasive for the following reasons:
1. The '909 patent teaches a pharmaceutical composition comprising an IgA antibody or functional fragment thereof, wherein constant rejection in the IgA antibody comprises mutations including P124R and N45.2G.
2. The teachings of Lohse et al. and Frazier et al and described above. Contrary to the presented arguments, the combination of '562 and the cited references, Lohse, Frazier and Pons teach or suggest all the elements of amended Claim 6.
The scientific reasoning and evidence as a whole indicates that the rejection should be maintained.
NEW CLAIM OBJECTIONS/REJECTIONS
Specification
The spacing of the lines of the specification is such as to make reading difficult. New application papers with lines 1 1/2 or double spaced (see 37 CFR 1.52(b)(2)) on good quality paper are required.
Claim Rejections-35 USC § 112(a) or 35 U.S.C. 112 (pre-AIA ), First paragraph, Written Description, New Matter
Claims 6, 8, 11, 20, 23, 24, 26-30 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 New Matter Rejection.
The specification as originally filed does not provide support for the invention as now claimed:
“..and IgA2 antibody with at least two mutations in a constant region of the IgA2 antibody wherein the at least two mutations are selected from the group consisting of N45.2G, P124R, C92S, N120T, I121L, T122S, deletion of C147 and deletion of Y148 relative to SEQ ID No: 3, numbering according to IMGT scheme..” (see claim 6).
Applicant's amendment, filed 16 March 2026, asserts that no new matter has been added and directs support to the original claims; lines 26-39 on page 3; lines 5-11 on page 10; lines 21-26 on page 22 and FIG. 3 for the written description for the above-mentioned “limitations”.
The Examiner cannot locate the wording or connotation of the instant claims from said sections.
The Examiner has found the following teachings:
“Antibodies having an IgA2.0 constant region were obtained by introducing the following substitution and deletions: N45.2G, P124R, C92S, N120T, I121L, T122S, deletion of C147 and deletion of Y148, numbering according to IMGT scheme. Additionally, an N135Q mutation (numbering according to IMGT scheme) can be introduced. In order to create an IgA3.0 constant region, 3-20 C-terminal amino acids can be removed (see FIG. 3E)” (paragraph 0126).
The instant claims result in New Matter because claim 6 has been amended to recite a Markush Group of substitution and deletions wherein a choice of at least two mutations can be chosen.
The specification, as originally filed, teaches antibodies having an IgA2.0 constant region were obtained by introducing N45.2G, P124R, C92S, N120T, I121L, T122S, deletion of C147 and deletion of Y148, numbering according to IMGT scheme.
The specification as filed does not provide a written description or set forth the metes and bounds of this "limitations". The instant claims now recite limitations which were not disclosed in the specification as filed, and now change the scope of the instant disclosure as-filed.
Applicant is required to cancel the new matter in the response to this Office action. Alternatively, Applicant is invited to provide specific written support for the “limitations” indicated above or rely upon the limitations set forth in the specification as filed.
Claim Rejections-35 USC § 112(a) or 35 U.S.C. 112 (pre-AIA ), First paragraph, Enablement
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 6, 8, 11, 20, 23, 24, 26-30 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 enablement requirement. The claim(s) 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.
The instant claims are drawn to a composition that comprises a first binding moiety and a second binding moiety, wherein said first binding moiety is an IgA2 antibody with at least two mutations in a constant region of the IgA2 antibody, wherein the at least two mutations are selected from the group consisting of N45.2G, P124R, C92S, N120T, I121L, T122S, deletion of C147 and deletion of Y148 relative to SEQ ID No: 3, numbering according to IMGT scheme, wherein the first binding moiety specifically binds CD89 and an extracellular membrane-bound antigen on cells in a tumor, wherein the extracellular membrane-bound antigen is an extracellular membrane-bound tumor antigen or an extracellular membrane-bound Treg antigen, wherein said second binding moiety is an antibody that specifically binds CD47 and blocks CD47 mediated signaling of SIRPa, and wherein the second binding moiety enhances neutrophil-mediated cytotoxicity of the first binding moiety on the tumor relative to the composition that lacks the second binding moiety.
The specification teaches that the invention relates to the field of antibodies, in particular to the field of therapeutic antibodies. The invention also relates to the field of immunotherapy, in particular to reducing immune response inhibitory processes in cancer. The invention provides a method for stimulating neutrophil-mediated killing of CD47 expressing cells. The method comprises contacting neutrophils with cells that express CD47 and another extracellular membrane-bound antigen in the presence of a first and a second binding moiety, wherein the first binding moiety specifically binds myeloid IgA receptor (CD89) and said antigen and wherein the second binding moiety specifically binds CD47 and blocks CD47 mediated signaling of SIRPa in the neutrophils.
Regarding the second binding moiety, which is an antibody that specifically binds CD47. The specification teaches Matlung et al., describe various antibodies that bind CD47 and that block the signaling of the molecules. Preferred CD47 binding antibodies are antibody C47A8-CQ described in EP2992089; 5A3-M5 described in US20140303354; and 2.3D11 described in US2018201677, which are incorporated by reference herein for specification of preferred CD47 binding antibodies and that block CD47-SIRPa signaling (page 7).
Regarding the first binding moiety, which is an IgA2 antibody with at least two mutations in a constant region of the IgA2. The specification teaches antibodies having an IgA2.0 constant region were obtained by introducing the following substitution and deletions: N45.2G, P124R, C92S, N120T, I121L, T122S, deletion of C147 and deletion of Y148, numbering according to IMGT scheme (page 22).
The specification is not enabled for the following reason:
1. While the specification teaches antibodies that specifically bind CD47 and block signaling (i.e. second binding moiety), the specification fails to teach how make an IgA2 antibody, comprising mutations N45.2G, P124R, C92S, N120T, I121L, T122S, deletion of C147 and deletion of Y148 relative to SEQ ID No: 3, numbering according to IMGT scheme (i.e. first binding moiety).
The specification fails to teach any information about the IMGT scheme.
For example, one of the recited mutations is P124R numbering according to IMGT scheme. Does P124R mean a proline (P) is being substituted with an arginine (R) at position 124?
2. The specification fails to teach the numbering of an IgA2 antibody according to the IMGT scheme.
3. The Examiner assumes the numbering of SEQ ID NO:3 is according to the Kabat numbering system.
The specification, however, fails to teach how the numbering of an IgA2 antibody according to the IMGT scheme correlates/is relative to the Kabat numbering system of SEQ ID NO:3.
For example, another recited mutation is N120T according to IMGT scheme relative to SEQ ID NO:3.
The specification fails to teach how N120T according to IMGT scheme is relative to the amino acid residue in SEQ ID NO:3.
The sequence listing of the instant specification teaches SEQ ID NO:3 as a human protein that comprises 355 amino acid residues. The amino acid sequence of SEQ ID NO:3 has a proline (Pro) at position 120.
Does N120T mean an asparagine (N) is being substituted with a threonine (T)?
Would N120T according to IMGT scheme correlate to a mutation being made in an amino acid residue at position 120 in SEQ ID NO:3? Would that mutation mean that a proline at position 120 in SEQ ID NO:3 is substituted with a threonine (T)?
4. As was stated above, the Examiner assumes the numbering of SEQ ID NO:3 is according to the Kabat numbering system. The Kabat numbering system does not teach amino acid residues at positions such as 45.2.
Thus, it is unclear how a mutation such as N45.2G numbering according to IMGT scheme correlates/is relative to an amino acid residue in SEQ ID NO:3?
In summary, it cannot be said that the specification provides the necessary guidance. The disclosure has to enable the artisan to make and use the claimed invention.
Due to the inherent unpredictability and the large quantity of experimentation necessary to determine the numbering of an IgA2 antibody according to the IMGT scheme and ascertain how the particular recited mutations in the IgA2 antibody numbering according to IMGT scheme correspond/is relative to Kabat numbering of SEQ ID NO:3; the lack of direction/guidance presented in the specification regarding same; the absence of working examples directed to same; and the complex nature of the invention; undue experimentation would be required of the skilled artisan to make and/or use the claimed invention.
Claim Rejections - 35 USC § 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph
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 6, 8, 11, 20, 23, 24, 26-30 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.
Claim 6 recites the acronym “IMGT”, which has not been defined in the claims. Acronyms should be defined upon their first use in a claim. The presence of an undefined acronym renders a claim indefinite. Claims 8, 11, 20, 23, 24, 26-30 are included in this rejection insofar as they depend from claim 6 and do not resolve the issue discussed above.
Claim 29 recites an amino acid sequence in the absence of a referenced SEQ ID NO. Please refer above to the “REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES”. The recitation of an amino acid sequence in the absence of a referenced SEQ ID NO renders the claims indefinite. The metes and bounds of claim 29 cannot be determined.
Claim Rejections - 35 USC § 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 30 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 30 recites, “The composition of claim 6, wherein said second binding moiety is the antibody that specifically binds CD47”
Claim 6 recites, “wherein said second binding moiety is an antibody that specifically binds CD47....”
Claim 30 does not further limit claim 6, because claim 6 already recites that the second binding moiety is an antibody that specifically binds CD47.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Conclusion
No claims are allowed.
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/R.M.D/Examiner, Art Unit 1647 3/25/2026
/JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647