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 .
Claims 1-30 are pending.
Applicant’s election of Group I that read on (A) agonist antibody to human PD-1 comprising antibody heavy chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 28 and an antibody light chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 42 wherein the antibody heavy chain variable region comprising CDR1 of SEQ ID NO: 357, CDR2 of SEQ ID NO: 358 and CDR3 of SEQ ID NO: 359, as well as an antibody light chain variable region comprising CDR1 of SEQ ID NO: 360, CDR2 of SEQ ID NO: 361 and CDR3 of SEQ ID NO: 362 as the species of antibody, (B) IgG1 as the species of Fc region, (C) S239D/S267G/H268D/K322A as the particular combination of substitution in the reply filed on June 2, 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)).
Claims 21-22 and 25-29 are withdrawn from further consideration by the examiner, 37 C.F.R. 1.142(b) as being drawn to non-elected inventions.
Claims 1-20, 23-24 and 30, drawn to an agonist antibody to human PD-1 or functional fragment thereof that read on (A) antibody heavy chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 28 and an antibody light chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 42 wherein the antibody heavy chain variable region comprising CDR1 of SEQ ID NO: 357, CDR2 of SEQ ID NO: 358 and CDR3 of SEQ ID NO: 359, as well as an antibody light chain variable region comprising CDR1 of SEQ ID NO: 360, CDR2 of SEQ ID NO: 361 and CDR3 of SEQ ID NO: 362 as the species of antibody, (B) IgG1 as the species of Fc region, (C) S239D/S267G/H268D/K322A as the particular combination of substitution, are being acted upon in this Office Action.
Priority
Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on February 23, 2026, Oct 31, 2025, June 3, 2025, February 14, 2024, February 9, 2024 and November 8, 2023 have been considered by the examiner and an initialed copy of the IDS is included with this Office Action.
The listing of references in the specification at pages 102-105 is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
The drawings filed on November 8, 2023 are acceptable.
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 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.
Amino acid sequences appearing in in Figure 2B which are not identified by sequence identifiers (SEQ ID NO:) either in the figure or in the Brief Description of the Figures in accordance with 37 CFR 1.821(d).
Nucleotide and/or Amino acid sequences appearing in in Tables I, II, III, IV, p. 84, line 2, which are not identified by sequence identifiers (SEQ ID NO:) in accordance with 37 CFR 1.821(d).
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) by inserting the required sequence identifiers or amendment to the Brief Description of the Drawings by inserting the corresponding Sequence Identifiers in Figure 2B.
amendment to the specification by inserting the corresponding Sequence Identifiers in Tables I, II, III, IV, and p. 84, line 2.
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 by inserting the required sequence identifier into the Brief Description of Drawings and Tables I, II, III, IV, and p. 84, line 2, 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.
Or
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/patents-application- process/filing-online/legal-framework-efs-web), 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.
Specification
The specification is objected to because the sequences in Table IV are eligible.
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant's cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Claim Objection
Claim 10 is objected to because of the following informality: duplicate “human FcγRIIA” should be deleted.
Claim Rejections - 35 USC § 112
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 1-20, 23-24 and 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 applicant regards as the invention.
Regarding claims 1-20, 23-24 and 30, the recitation of “functional fragment” is indefinite and ambiguous because it is not clear if the “functional fragment” is referring to the antigen-binding fragment or the Fc fragment thereof. One skilled in the art could not determine the boundaries of the claimed invention in order to avoid infringing on the claim. Amending the claims to recite “antigen-binding fragment” would obvious this rejection.
Claim 6 recites the limitation "the antibody heavy chain constant region" in claim 1. There is insufficient antecedent basis for this limitation in the claim. Amending claim 6 to recite “wherein the antibody comprises a human heavy chain constant region and a human light chain constant region” would obviate this rejection.
Claim 7 recites the limitation "the antibody heavy chain constant region" in claim 1. There is insufficient antecedent basis for this limitation in the claim. Amending claim 7 to recite “wherein the antibody comprises a heavy chain constant region of human IgG” would obviate this rejection.
Claim 9 recites the limitation "the antibody light chain constant region" in claim 1. There is insufficient antecedent basis for this limitation in the claim. Amending claim 9 to recite “wherein the antibody comprises a light chain constant region of human Igκ” would obviate this rejection.
Regarding claims 13, 14, 15, the phrases "more preferably" and “still more preferably” render the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 16, the phrases “preferably", “more preferably” and “still more preferably” render the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim rejections under - 35 U.S.C. 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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, 4, 6-20, 24 and 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP § 2163 lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed, and correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art. “Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.”
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.
Claim 1 encompasses any agonist antibody to human PD-1 or a functional fragment thereof, wherein the antibody or a functional fragment thereof binds to domain #7 as shown in SEQ ID NO: 9, of human PD-1.
Claim 2 encompasses the antibody or a functional fragment thereof of claim 1, wherein the antibody or a functional fragment thereof has any one of (A) to (D) below:
(A) an antibody heavy chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 17 and an antibody light chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 34;
(B) an antibody heavy chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 22 and an antibody light chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 38;
(C) an antibody heavy chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 28 and an antibody light chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 42; or
(D) an antibody heavy chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 33 and an antibody light chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 46.
Claim 3 encompasses the antibody or a functional fragment thereof of claim 1, wherein the antibody or a functional fragment thereof has either the following (A) to (D) below:
(A) an antibody heavy chain variable region comprising complementarity determining region (CDR) 1 of SEQ ID NO: 345, CDR2 of SEQ ID NO: 346 and CDR3 of SEQ ID NO: 347, as well as an antibody light chain variable region comprising CDR1 of SEQ ID NO: 348, CDR2 of SEQ ID NO: 349 and CDR3 of SEQ ID NO: 350;
(B) an antibody heavy chain variable region comprising CDR1 of SEQ ID NO: 351, CDR2 of SEQ ID NO: 352 and CDR3 of SEQ ID NO: 353, as well as an antibody light chain variable region comprising CDR1 of SEQ ID NO: 354, CDR2 of SEQ ID NO: 355 and CDR3 of SEQ ID NO: 356;
(C) an antibody heavy chain variable region comprising CDR1 of SEQ ID NO: 357, CDR2 of SEQ ID NO: 358 and CDR3 of SEQ ID NO: 359, as well as an antibody light chain variable region comprising CDR1 of SEQ ID NO: 360, CDR2 of SEQ ID NO: 361 and CDR3 of SEQ ID NO: 362; or
(D) an antibody heavy chain variable region comprising CDR1 of SEQ ID NO: 363, CDR2 of SEQ ID NO: 364 and CDR3 of SEQ ID NO: 365, as well as an antibody light chain variable region comprising CDR1 of SEQ ID NO: 366, CDR2 of SEQ ID NO: 367 and CDR3 of SEQ ID NO: 368.
Claim 4 encompasses the antibody or a functional fragment thereof of claim 1, wherein the antibody variable region comprises the framework of human antibody or the framework of humanized antibody.
Claim 5 encompasses the antibody or a functional fragment thereof of claim 1, wherein the antibody or a functional fragment thereof has either the following (A) to (D) below:
(A) an antibody heavy chain variable region having the amino acid sequence as shown in SEQ ID NO: 20 and a light chain variable region having the amino acid sequence as shown in SEQ ID NO: 37;
(B) an antibody heavy chain variable region having the amino acid sequence as shown in SEQ ID NO: 21 and a light chain variable region having the amino acid sequence as shown in SEQ ID NO: 37;
(C) an antibody heavy chain variable region having the amino acid sequence as shown in SEQ ID NO: 26 and a light chain variable region having the amino acid sequence as shown in SEQ ID NO: 40; or
(D) an antibody heavy chain variable region having the amino acid sequence as shown in SEQ ID NO: 30 and a light chain variable region having the amino acid sequence as shown in SEQ ID NO: 44.
Claim 6 encompasses the antibody or a functional fragment thereof of claim 1, wherein the antibody heavy chain constant region and the antibody light chain constant region comprise an amino acid sequence derived from human antibody.
Claim 7 encompasses the antibody or a functional fragment thereof of claim 1, wherein the antibody heavy chain constant region is the antibody heavy chain constant region of human IgG.
Claim 8 encompasses the antibody or a functional fragment thereof of claim 7, wherein the antibody heavy chain constant region of said human IgG is the antibody heavy chain constant region of human IgG1.
Claim 9 encompasses the antibody or a functional fragment thereof of claim 1, wherein the antibody light chain constant region is the antibody light chain constant region of human IgK.
Claim 10 encompasses the antibody or a functional fragment thereof of claim 1, wherein the antibody or a functional fragment thereof has an improved affinity to any one or more of the following receptors: human FcyRIIA, human FcyRIIB or human FcyRIIA.
Claim 11 encompasses the antibody or a functional fragment thereof of claim 1, wherein the antibody or a functional fragment thereof has an improved affinity to human FcyRIIB.
Claim 12 encompasses the antibody or a functional fragment thereof of claim 1, wherein the antibody or a functional fragment thereof has an improved affinity to human FcγRIIIa.
Claim 13 encompasses the antibody or a functional fragment thereof of claim 11, wherein the improvement of affinity to human FcyRIIB is, compared to a reference antibody having the Fc region of human IgG1-K322A, by 1.5 folds or more, preferably by 2.0 folds or more, and still more preferably by 2.5 folds or more, in a test measuring Fc receptor binding affinity using the surface plasmon resonance technique.
Claim 14 encompasses the antibody or a functional fragment thereof of claim 11, wherein the improvement of affinity to human FcyRIIB is, compared to a reference antibody having the Fc region of human IgG1-K322A, by 2 folds or more, preferably by 5 folds or more, and still more preferably by 20 folds or more, in a test of measuring the affinity to a human Fc receptor-expressing cell line with a flow cytometer.
Claim 15 encompasses the antibody or a functional fragment thereof of claim 12, wherein the improvement of affinity to human FcγRIIIa is, compared to a reference antibody having the Fc region of human IgG1-K322A, by 1.5 folds or more, preferably by 2.0 folds or more, and still more preferably by 2.5 folds or more, in a test measuring Fc receptor binding affinity using the surface plasmon resonance technique.
Claim 16 encompasses the antibody or a functional fragment thereof of claim 12, wherein the improvement of affinity to human FcγRIIIa is, compared to a reference antibody having the Fc region of human IgG1-K322A, by 1.5 folds or more, preferably by 2.0 folds or more, still more preferably by 4.0 folds or more, and most preferably by 5.0 folds or more, in a test of measuring the affinity to a human Fc receptor-expressing cell line with a flow cytometer.
Claim 17 encompasses the antibody or a functional fragment thereof of claim 10, wherein the antibody or a functional fragment has a modified Fc region of human IgG, and the affinity of the antibody or a functional fragment thereof to said receptor has been improved by modification of the Fc region of human IgG.
Claim 18 encompasses the antibody or a functional fragment thereof of claim 10, wherein the antibody or a functional fragment has a modified Fc region of human IgG1 or human IgG4, and the affinity of the antibody or a functional fragment thereof to said receptor has been improved by modification of the Fc region of human IgG1 or human IgG4.
Claim 19 encompasses the antibody or a functional fragment thereof of claim 10, wherein any of the amino acids at positions 233, 234, 236, 237, 238, 239, 267, 268, 271, 296, 323, 326, 328, 330 and 332 (according to EU numbering) in the amino acid sequence of the Fc region of human IgGl is modified.
Claim 20 encompasses the antibody or a functional fragment thereof of claim 19, wherein the modification of amino acids is any one of the combinations G236D/H268D, S239D/H268D, S239D/H268D/L328Y/1332E, G236D/H268D/K322A, S239D/H268D/K322A, S239D/S267G/H268D/K322A, G236D/H268D/E293A/K322A, S239D/H268D/K322A/L328Y/1332E, S239D/H268D/E293A/K322A, S239D/S267G/H268D/K322A/L328Y, S239D/S267G/H268D/K322A/1332E, S239D/H268D/K322A/L328Y, S239D/H268D/K322A/1332E, S239D/S267G/H268D/K322A/L328Y/1332E, E233D/G237D/P238D/H268D/P271G/A330R and S267E/L328F.
Claim 21 encompasses the antibody or a functional fragment thereof of claim 10, wherein any of the amino acids at positions 236, 239, 268, 328 and 332 (according to EU numbering) in the amino acid sequence of the Fc region of human IgG4 is modified.
Claim 22 encompasses the antibody or a functional fragment thereof of claim 21, wherein the modification of amino acids is any one of the combinations S228P/G236D/Q268D, S228P/S239D/Q268D, and S228P/S239D/Q268D/L328Y/1332E.
Claim 23 encompasses the antibody or a functional fragment thereof of claim 10, wherein the antibody comprises either the following (A) to (D) below:
(A) an antibody heavy chain sequence having the amino acid sequence as shown in SEQ ID NO: 245 and an antibody light chain sequence having the amino acid sequence as shown in SEQ ID NO: 247;
(B) an antibody heavy chain sequence having the amino acid sequence as shown in SEQ ID NO: 277 and an antibody light chain sequence having the amino acid sequence as shown in SEQ ID NO: 279;
(C) an antibody heavy chain sequence having the amino acid sequence as shown in SEQ ID NO: 285 and an antibody light chain sequence having the amino acid sequence as shown in SEQ ID NO: 287; or
(D) an antibody heavy chain sequence having the amino acid sequence as shown in SEQ ID NO: 289 and an antibody light chain sequence having the amino acid sequence as shown in SEQ ID NO: 291.
Claim 24 encompasses the antibody or a functional fragment thereof of claim 12, wherein the antibody or a functional fragment thereof is defucosylated.
Claim 30 encompasses a pharmaceutical composition comprising the antibody or a functional fragment thereof of claim 1 and a pharmaceutically acceptable carrier.
The specification disclose just four agonist antibodies HM242, HM266, HM268 and HM297 that bind to human PD-1 epitope as shown in SEQ ID NO: 9 wherein each of the antibody comprises a combination of six heavy and light chain CDRs as shown in Table 1 and recited in claims 1 and 3. The antibodies each comprises a heavy chain variable region and a light chain variable region having the amino acid sequences as shown in Tables II and III and recited in claim 5. The human IgG1 Fc region of the antibodies each comprises G266D/H268D, S239D/H268D, S239D/H268D/L328Y/I332E, G268D/H268D/K372A or S239D/H268D/K322A substitutions as shown in Table IV.
However, the specification does not describe i. Complete structure, e.g., amino acid sequences of heavy and light chains variable domains, ii. Partial structure, e.g., six CDRs and functional features share by members of the genus of antibodies or antigen binding fragment thereof that correlated with binding to domain #7 shown in SEQ ID NO: 9. An adequate written description must contain enough information about the actual makeup of the claimed products – “a precise definition, such as structure, formula, chemic name, physical properties of other properties, of species falling with the genus sufficient to distinguish the gene from other materials”, which may be present in “functional terminology when the art has established a correlation between structure and function” (Amgen page 1361).
The specification does not describe a representative number of species falling within the scope of the genus or structural features common to the members of the genus so the one of skill in the art can visualize or recognize the member of the genus of the actual claimed antibody or antigen-binding fragment thereof that bind to domain #7 shown in SEQ ID NO: 9 of the actual claimed antibodies or functional fragment thereof themselves.
At the time the invention was made, it was known in the art that antibodies have a large repertoire of distinct structures and that a huge variety of antibodies can be made to bind to a single epitope.
For example, Lloyd et al. taught that hundreds of functional antibody fragments can be isolated from an antibody library that bind to the same antigen wherein these antibodies have distinct heavy and light chain sequences (Lloyd et al. Protein Engineering, Design & Selection 2009, 22:159-168; see, e.g., Discussion).
Similarly, Edwards et al., J Mol Biol. 2003 Nov 14;334(1): 103-118, found that over 1000 antibodies, all different in amino acid sequence, were generated to a single protein; 568 different amino acid sequences identified for the V(H) CDR3 domains of these antibodies (Abstract).
Piche-Nicholas et al MABS 10(1): 81-94, 2018; PTO 892) teaches altering complementary-determining region (CDRs) by 1-5 mutations significantly alter binding affinity to FcRn in vitro, see entire document, abstract, p. 95, right col, in particular. Engineering CDRs by modify local charge and thus maintain affinity to FcRn at 400 nM or weaker in vitro while retaining antigen binding may have far-reaching implications in the half-life optimization efforts of IgG therapeutics with respect to in vivo pharmacokinetics, see p. 90, in particular. Given that hundreds of unique antibody structures may bind a single antigen, the structure of an antibody cannot be predicted from the structure of the antigen (as held in Amgen), and a single species, or small group of species, cannot define a structure-function relationship so as to be representative of all the antibodies that bind to that antigen (as held in Abbvie).
Regarding the antibody heavy chain constant region and the antibody light chain constant region comprise an amino acid sequence derived from human antibody (claim 6), the term “derived” encompasses derivatives, e.g., substitution, deletion, addition or a combination thereof.
The specification discloses humanized antibodies wherein the Fc is from human IgG1 Fc, see Table II.
However, the specification does not teach any substitutions, deletion, addition or combination wherein the Fc still maintains binding to FcRn and effector functions to demonstrate possession at the time of filing. Note, deleting “derived” in claim 6 would obviate this issue.
Regarding antibody or functional fragment thereof that has improved affinity to any one or more human FcγRIIA, human FcγRIIB, human FcγRIIIA (claims 10-12) having improved affinity to human FcγRIIB by 1.5, 2.0, or 2.5 fold or more (claims 13-14) or having improved affinity to human FcγRIIIA by 1.5, 2.0, or 2.5 fold or more as compared to the Fc region of human IgG1 having K322A using surface plasmon resonance technique, the specification discloses the particular combination of substitutions in the Fc region of human IgG1 as shown in Table IV.
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However, the specification does not describe which one of such combination of substitutions in Table IV correlated with improved affinity to human FcγRIIB by 1.5, 2.0, 2.5 or more fold, and which one correlated with improved affinity to human FcγRIIIA by 1.5 fold, 2.0, 2.5 or more fold compared to the Fc region of human IgG1 having K322A.
For example, Moore et al (mAbs 2(2): 181-189, 2010; PTO 892) teaches that the triple mutation Ser267Glu, His268Phe, and serine 324 threonine (Ser324Thr) has been found to largely improve CDC at the expense of reduced ADCC and ADCP via increasing the affinity to inhibitory FcγRIIb, see entire document, Table 3, p. 186, right col.
Thus, it appears that the instant specification does not adequately disclose the breadth of the agonist antibody to human PD-1 or functional fragment thereof that binds to the sequence as shown in SEQ ID NO: 9 wherein the antibody or any functional fragment thereof has improved affinity to any one or more human Fcγ receptors, such as FcγRIIa, FcγRIIB, FcγRIIIA wherein the antibody has any modification, substitution, deletion, addition or a combination thereof at positions 233, 234, 236, 237, 238, 239, 267, 268, 271, 296, 323, 326, 328, 330 and 332 (according to EU numbering) in the amino acid sequence of the Fc region of human IgGl is modified. In light of this, a skilled artisan would reasonably conclude that Applicant was not in possession of the genus of all the said agonist antibody or functional fragment thereof at the time the instant application was filed.
While the Federal Circuit has recognized that “the written description requirement can in some cases be satisfied by functional description,” it has made clear that “such functional description can be sufficient only if there is also a structure-function relationship known to those of ordinary skill in the art.” In re Wallach, 378 F.3d 1330, 1335 (Fed. Cir. 2004); see also, Enzo Biochem, Inc. v. Gen-Probe, Inc.,323 F.3d 956, 964 (Fed. Cir. 2002) (holding that the written description requirement would be satisfied “if the functional characteristic of preferential binding . . . were coupled with a disclosed correlation between that function and a structure that is sufficiently known or disclosed”).
Amgen Inc. v. Sanofi, 782 F.3d 1367, 1378 (Fed. Cir. 2017) (holding that an “adequate written description must contain enough information about the actual makeup of the claimed products”). Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the "newly characterized" test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1345 (Fed. Cir. 2010).
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear 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.).
Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddles v. Baird, 30 USPQ2d 1481, 1483. In Fiddles v. Baird, claims directed to mammalian FGF’s were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence. Thus, the specification fails to describe these DNA sequences.
For genus claims, an adequate written description of a claimed genus requires more than a generic statement of an invention's boundaries. A patent must set forth either a representative number of species falling within the scope of the genus or structural features common to the members of the genus. Kubin, Exparte, 83 USPQ2d 1410 (Bd. Pat. App. & Int. 2007); Ariad Pharms., Inc. v. Eli Lilly& Co., 598 F.3d 1336, 1350 (Fed. Cir. 2010).
Therefore, only (1) an agonist antibody or antigen binding fragment thereof that binds to epitope shown in SEQ ID NO: 9, wherein the antibody or antigen binding fragment thereof has any one of (A) to (D) below:
(A) an antibody heavy chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 17 and an antibody light chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 34;
(B) an antibody heavy chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 22 and an antibody light chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 38;
(C) an antibody heavy chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 28 and an antibody light chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 42; or
(D) an antibody heavy chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 33 and an antibody light chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 46,
(2) the agonist antibody or antigen binding fragment thereof above, wherein the antibody or a functional fragment thereof has either the following (A) to (D) below:
(A) an antibody heavy chain variable region comprising complementarity determining region (CDR) 1 of SEQ ID NO: 345, CDR2 of SEQ ID NO: 346 and CDR3 of SEQ ID NO: 347, as well as an antibody light chain variable region comprising CDR1 of SEQ ID NO: 348, CDR2 of SEQ ID NO: 349 and CDR3 of SEQ ID NO: 350;
(B) an antibody heavy chain variable region comprising CDR1 of SEQ ID NO: 351, CDR2 of SEQ ID NO: 352 and CDR3 of SEQ ID NO: 353, as well as an antibody light chain variable region comprising CDR1 of SEQ ID NO: 354, CDR2 of SEQ ID NO: 355 and CDR3 of SEQ ID NO: 356;
(C) an antibody heavy chain variable region comprising CDR1 of SEQ ID NO: 357, CDR2 of SEQ ID NO: 358 and CDR3 of SEQ ID NO: 359, as well as an antibody light chain variable region comprising CDR1 of SEQ ID NO: 360, CDR2 of SEQ ID NO: 361 and CDR3 of SEQ ID NO: 362; or
(D) an antibody heavy chain variable region comprising CDR1 of SEQ ID NO: 363, CDR2 of SEQ ID NO: 364 and CDR3 of SEQ ID NO: 365, as well as an antibody light chain variable region comprising CDR1 of SEQ ID NO: 366, CDR2 of SEQ ID NO: 367 and CDR3 of SEQ ID NO: 368,
(3) the agonist antibody or antigen binding fragment thereof above, wherein the antibody or a functional fragment thereof comprising either the following (A) to (D) below:
(A) an antibody heavy chain variable region having the amino acid sequence as shown in SEQ ID NO: 20 and a light chain variable region having the amino acid sequence as shown in SEQ ID NO: 37;
(B) an antibody heavy chain variable region having the amino acid sequence as shown in SEQ ID NO: 21 and a light chain variable region having the amino acid sequence as shown in SEQ ID NO: 37;
(C) an antibody heavy chain variable region having the amino acid sequence as shown in SEQ ID NO: 26 and a light chain variable region having the amino acid sequence as shown in SEQ ID NO: 40; or
(D) an antibody heavy chain variable region having the amino acid sequence as shown in SEQ ID NO: 30 and a light chain variable region having the amino acid sequence as shown in SEQ ID NO: 44,
(4) the antibody or antigen binding fragment thereof above, wherein the antibody is humanized,
(5) the agonist antibody or antigen binding fragment thereof above, wherein the antibody heavy chain variable region further comprises a human IgG1 or human IgG4 Fc,
(6) the agonist antibody or antigen binding fragment thereof above, wherein the antibody has improved affinity to human FcγRIIB and FcγRIIIA,
(7) the agonist antibody or antigen binding fragment thereof above, wherein the human IgG1 Fc comprises one of the following combination of substitution G236D/H268D, S239D/H268D, S239D/H268D/L328Y/1332E, G236D/H268D/K322A, S239D/H268D/K322A, S239D/S267G/H268D/K322A, G236D/H268D/E293A/K322A, S239D/H268D/K322A/L328Y/1332E, S239D/H268D/E293A/K322A, S239D/S267G/H268D/K322A/L328Y, S239D/S267G/H268D/K322A/1332E, S239D/H268D/K322A/L328Y, S239D/H268D/K322A/1332E, S239D/S267G/H268D/K322A/L328Y/1332E, E233D/G237D/P238D/H268D/P271G/A330R and S267E/L328F, but not the full breadth of the claims meets the written description provision of 35 U.S.C. § 112, first paragraph. 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 1, 4, 6-20, 24 and 30 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 (1) an agonist antibody or antigen binding fragment thereof that binds to epitope shown in SEQ ID NO: 9 comprising the six CDRs as set forth in claims 2 and 3, (2) the agonist antibody or antigen binding fragment thereof comprising a heavy chain variable region amino acid sequence and a light chain variable region amino acid sequence as set forth in claim 5, (3) the agonist antibody or antigen binding fragment thereof comprising a heavy chain amino acid sequence and a light chain amino acid sequence as set forth in claim 23, (4) (4) the antibody or antigen binding fragment thereof above, wherein the antibody is humanized,
(5) the agonist antibody or antigen binding fragment thereof above, wherein the antibody heavy chain variable region further comprises a human IgG1 or human IgG4 Fc,
(6) the agonist antibody or antigen binding fragment thereof above, wherein the antibody has improved affinity to human FcγRIIB and FcγRIIIA,
(7) the agonist antibody or antigen binding fragment thereof above, wherein the human IgG1 Fc comprises one of the following combination of substitution G236D/H268D, S239D/H268D, S239D/H268D/L328Y/1332E, G236D/H268D/K322A, S239D/H268D/K322A, S239D/S267G/H268D/K322A, G236D/H268D/E293A/K322A, S239D/H268D/K322A/L328Y/1332E, S239D/H268D/E293A/K322A, S239D/S267G/H268D/K322A/L328Y, S239D/S267G/H268D/K322A/1332E, S239D/H268D/K322A/L328Y, S239D/H268D/K322A/1332E, S239D/S267G/H268D/K322A/L328Y/1332E, E233D/G237D/P238D/H268D/P271G/A330R and S267E/L328F for treating autoimmune disease, does not reasonably provide enablement for any agonist antibody or functional fragment thereof as set forth in claims 1, 4, 6-20, 24 and 30. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01(a)). These factors include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. . In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
Claim 1 encompasses any agonist antibody to human PD-1 or a functional fragment thereof, wherein the antibody or a functional fragment thereof binds to domain #7 as shown in SEQ ID NO: 9, of human PD-1.
Claim 2 encompasses the antibody or a functional fragment thereof of claim 1, wherein the antibody or a functional fragment thereof has any one of (A) to (D) below:
(A) an antibody heavy chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 17 and an antibody light chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 34;
(B) an antibody heavy chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 22 and an antibody light chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 38;
(C) an antibody heavy chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 28 and an antibody light chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 42; or
(D) an antibody heavy chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 33 and an antibody light chain variable region sequence comprising CDR1, CDR2 and CDR3 in the amino acid sequence as shown in SEQ ID NO: 46.
Claim 3 encompasses the antibody or a functional fragment thereof of claim 1, wherein the antibody or a functional fragment thereof has either the following (A) to (D) below:
(A) an antibody heavy chain variable region comprising complementarity determining region (CDR) 1 of SEQ ID NO: 345, CDR2 of SEQ ID NO: 346 and CDR3 of SEQ ID NO: 347, as well as an antibody light chain variable region comprising CDR1 of SEQ ID NO: 348, CDR2 of SEQ ID NO: 349 and CDR3 of SEQ ID NO: 350;
(B) an antibody heavy chain variable region comprising CDR1 of SEQ ID NO: 351, CDR2 of SEQ ID NO: 352 and CDR3 of SEQ ID NO: 353, as well as an antibody light chain variable region comprising CDR1 of SEQ ID NO: 354, CDR2 of SEQ ID NO: 355 and CDR3 of SEQ ID NO: 356;
(C) an antibody heavy chain variable region comprising CDR1 of SEQ ID NO: 357, CDR2 of SEQ ID NO: 358 and CDR3 of SEQ ID NO: 359, as well as an antibody light chain variable region comprising CDR1 of SEQ ID NO: 360, CDR2 of SEQ ID NO: 361 and CDR3 of SEQ ID NO: 362; or
(D) an antibody heavy chain variable region comprising CDR1 of SEQ ID NO: 363, CDR2 of SEQ ID NO: 364 and CDR3 of SEQ ID NO: 365, as well as an antibody light chain variable region comprising CDR1 of SEQ ID NO: 366, CDR2 of SEQ ID NO: 367 and CDR3 of SEQ ID NO: 368.
Claim 4 encompasses the antibody or a functional fragment thereof of claim 1, wherein the antibody variable region comprises the framework of human antibody or the framework of humanized antibody.
Claim 5 encompasses the antibody or a functional fragment thereof of claim 1, wherein the antibody or a functional fragment thereof has either the following (A) to (D) below:
(A) an antibody heavy chain variable region having the amino acid sequence as shown in SEQ ID NO: 20 and a light chain variable region having the amino acid sequence as shown in SEQ ID NO: 37;
(B) an antibody heavy chain variable region having the amino acid sequence as shown in SEQ ID NO: 21 and a light chain variable region having the amino acid sequence as shown in SEQ ID NO: 37;
(C) an antibody heavy chain variable region having the amino acid sequence as shown in SEQ ID NO: 26 and a light chain variable region having the amino acid sequence as shown in SEQ ID NO: 40; or
(D) an antibody heavy chain variable region having the amino acid sequence as shown in SEQ ID NO: 30 and a light chain variable region having the amino acid sequence as shown in SEQ ID NO: 44.
Claim 6 encompasses the antibody or a functional fragment thereof of claim 1, wherein the antibody heavy chain constant region and the antibody light chain constant region comprise an amino acid sequence derived from human antibody.
Claim 7 encompasses the antibody or a functional fragment thereof of claim 1, wherein the antibody heavy chain constant region is the antibody heavy chain constant region of human IgG.
Claim 8 encompasses the antibody or a functional fragment thereof of claim 7, wherein the antibody heavy chain constant region of said human IgG is the antibody heavy chain constant region of human IgG1.
Claim 9 encompasses the antibody or a functional fragment thereof of claim 1, wherein the antibody light chain constant region is the antibody light chain constant region of human IgK.
Claim 10 encompasses the antibody or a functional fragment thereof of claim 1, wherein the antibody or a functional fragment thereof has an improved affinity to any one or more of the following receptors: human FcyRIIA, human FcyRIIB or human FcyRIIA.
Claim 11 encompasses the antibody or a functional fragment thereof of claim 1, wherein the antibody or a functional fragment thereof has an improved affinity to human FcyRIIB.
Claim 12 encompasses the antibody or a functional fragment thereof of claim 1, wherein the antibody or a functional fragment thereof has an improved affinity to human FcyRIIIA.
Claim 13 encompasses the antibody or a functional fragment thereof of claim 11, wherein the improvement of affinity to human FcyRIIB is, compared to a reference antibody having the Fc region of human IgG1-K322A, by 1.5 folds or more, preferably by 2.0 folds or more, and still more preferably by 2.5 folds or more, in a test measuring Fc receptor binding affinity using the surface plasmon resonance technique.
Claim 14 encompasses the antibody or a functional fragment thereof of claim 11, wherein the improvement of affinity to human FcyRIIB is, compared to a reference antibody having the Fc region of human IgG1-K322A, by 2 folds or more, preferably by 5 folds or more, and still more preferably by 20 folds or more, in a test of measuring the affinity to a human Fc receptor-expressing cell line with a flow cytometer.
Claim 15 encompasses the antibody or a functional fragment thereof of claim 12, wherein the improvement of affinity to human FcyRIIIA is, compared to a reference antibody having the Fc region of human IgG1-K322A, by 1.5 folds or more, preferably by 2.0 folds or more, and still more preferably by 2.5 folds or more, in a test measuring Fc receptor binding affinity using the surface plasmon resonance technique.
Claim 16 encompasses the antibody or a functional fragment thereof of claim 12, wherein the improvement of affinity to human FcyRIIIA is, compared to a reference antibody having the Fc region of human IgG1-K322A, by 1.5 folds or more, preferably by 2.0 folds or more, still more preferably by 4.0 folds or more, and most preferably by 5.0 folds or more, in a test of measuring the affinity to a human Fc receptor-expressing cell line with a flow cytometer.
Claim 17 encompasses the antibody or a functional fragment thereof of claim 10, wherein the antibody or a functional fragment has a modified Fc region of human IgG, and the affinity of the antibody or a functional fragment thereof to said receptor has been improved by modification of the Fc region of human IgG.
Claim 18 encompasses the antibody or a functional fragment thereof of claim 10, wherein the antibody or a functional fragment has a modified Fc region of human IgG1 or human IgG4, and the affinity of the antibody or a functional fragment thereof to said receptor has been improved by modification of the Fc region of human IgG1 or human IgG4.
Claim 19 encompasses the antibody or a functional fragment thereof of claim 10, wherein any of the amino acids at positions 233, 234, 236, 237, 238, 239, 267, 268, 271, 296, 323, 326, 328, 330 and 332 (according to EU numbering) in the amino acid sequence of the Fc region of human IgGl is modified.
Claim 20 encompasses the antibody or a functional fragment thereof of claim 19, wherein the modification of amino acids is any one of the combinations G236D/H268D, S239D/H268D, S239D/H268D/L328Y/1332E, G236D/H268D/K322A, S239D/H268D/K322A, S239D/S267G/H268D/K322A, G236D/H268D/E293A/K322A, S239D/H268D/K322A/L328Y/1332E, S239D/H268D/E293A/K322A, S239D/S267G/H268D/K322A/L328Y, S239D/S267G/H268D/K322A/1332E, S239D/H268D/K322A/L328Y, S239D/H268D/K322A/1332E, S239D/S267G/H268D/K322A/L328Y/1332E, E233D/G237D/P238D/H268D/P271G/A330R and S267E/L328F.
Claim 21 encompasses the antibody or a functional fragment thereof of claim 10, wherein any of the amino acids at positions 236, 239, 268, 328 and 332 (according to EU numbering) in the amino acid sequence of the Fc region of human IgG4 is modified.
Claim 22 encompasses the antibody or a functional fragment thereof of claim 21, wherein the modification of amino acids is any one of the combinations S228P/G236D/Q268D, S228P/S239D/Q268D, and S228P/S239D/Q268D/L328Y/1332E.
Claim 23 encompasses the antibody or a functional fragment thereof of claim 10, wherein the antibody comprises either the following (A) to (D) below:
(A) an antibody heavy chain sequence having the amino acid sequence as shown in SEQ ID NO: 245 and an antibody light chain sequence having the amino acid sequence as shown in SEQ ID NO: 247;
(B) an antibody heavy chain sequence having the amino acid sequence as shown in SEQ ID NO: 277 and an antibody light chain sequence having the amino acid sequence as shown in SEQ ID NO: 279;
(C) an antibody heavy chain sequence having the amino acid sequence as shown in SEQ ID NO: 285 and an antibody light chain sequence having the amino acid sequence as shown in SEQ ID NO: 287; or
(D) an antibody heavy chain sequence having the amino acid sequence as shown in SEQ ID NO: 289 and an antibody light chain sequence having the amino acid sequence as shown in SEQ ID NO: 291.
Claim 24 encompasses the antibody or a functional fragment thereof of claim 12, wherein the antibody or a functional fragment thereof is defucosylated.
Claim 30 encompasses a pharmaceutical composition comprising the antibody or a functional fragment thereof of claim 1 and a pharmaceutically acceptable carrier.
The specification disclose just four agonist antibodies HM242, HM266, HM268 and HM297 that bind to human PD-1 epitope as shown in SEQ ID NO: 9 wherein each of the antibody comprises a combination of six heavy and light chain CDRs as shown in Table 1 and recited in claims 1 and 3. The antibodies each comprises a heavy chain variable region and a light chain variable region having the amino acid sequences as shown in Tables II and III and recited in claim 5. The human IgG1 Fc region of the antibodies each comprises G266D/H268D, S239D/H268D, S239D/H268D/L328Y/I332E, G268D/H268D/K372A or S239D/H268D/K322A substitutions as shown in Table IV.
However, the specification does not teach i. Complete structure, e.g., amino acid sequences of heavy and light chains variable domains, ii. Partial structure, e.g., six CDRs and functional features share by members of the genus of antibodies or antigen binding fragment thereof that correlated with binding to domain #7 shown in SEQ ID NO: 9.
The specification does not enable one of skill in the art to make and use the genus of antibody or antigen-binding fragment thereof that bind to domain #7 shown in SEQ ID NO: 9 of the actual claimed antibodies or functional fragment thereof without undue experimentation.
At the time the invention was made, it was known in the art that antibodies have a large repertoire of distinct structures and that a huge variety of antibodies can be made to bind to a single epitope.
For example, Lloyd et al. taught that hundreds of functional antibody fragments can be isolated from an antibody library that bind to the same antigen wherein these antibodies have distinct heavy and light chain sequences (Lloyd et al. Protein Engineering, Design & Selection 22:159-168, 2009; PTO 892; see, e.g., Discussion).
Similarly, Edwards et al., J Mol Biol. 334(1): 103-118, 2003; PTO 892, found that over 1000 antibodies, all different in amino acid sequence, were generated to a single protein; 568 different amino acid sequences identified for the V(H) CDR3 domains of these antibodies (Abstract).
Piche-Nicholas et al MABS 10(1): 81-94, 2018; PTO 892) teaches altering complementary-determining region (CDRs) by 1-5 mutations significantly alter binding affinity to FcRn in vitro, see entire document, abstract, p. 95, right col, in particular. Engineering CDRs by modify local charge and thus maintain affinity to FcRn at 400 nM or weaker in vitro while retaining antigen binding may have far-reaching implications in the half-life optimization efforts of IgG therapeutics with respect to in vivo pharmacokinetics, see p. 90, in particular. Given that hundreds of unique antibody structures may bind a single antigen, the structure of an antibody cannot be predicted from the structure of the antigen, and a single species, or small group of species, cannot define a structure-function relationship so as to be representative of all the antibodies that bind to that antigen.
Regarding the antibody heavy chain constant region and the antibody light chain constant region comprise an amino acid sequence derived from human antibody (claim 6), the term “derived” encompasses derivatives, e.g., substitution, deletion, addition or a combination thereof.
The specification discloses humanized antibodies wherein the Fc is from human IgG1 Fc, see Table II.
However, the specification does not teach any substitutions, deletion, addition or combination wherein the full-length sequence of Fc still maintains binding to FcRn and effector functions to demonstrate possession at the time of filing. Note, deleting “derived” in claim 6 would obviate this issue.
Regarding antibody or functional fragment thereof that has improved affinity to any one or more human FcγRIIA, human FcγRIIB, human FcγRIIIA (claims 10-12) having improved affinity to human FcγRIIB by 1.5, 2.0, or 2.5 fold or more (claims 13-14) or having improved affinity to human FcγRIIIA by 1.5, 2.0, or 2.5 fold or more as compared to the Fc region of human IgG1 having K322A using surface plasmon resonance technique, the specification discloses the particular combination of substitutions in the Fc region of human IgG1 as shown in Table IV.
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However, the specification does not teach which one of such combination of substitutions in Table IV correlated with improved affinity to human FcγRIIB by 1.5, 2.0, 2.5 or more fold, and which one correlated with improved affinity to human FcγRIIIA by 1.5 fold, 2.0, 2.5 or more fold compared to the Fc region of human IgG1 having K322A.
For example, Moore et al (mAbs 2(2): 181-189, 2010; PTO 892) teaches that the triple mutation Ser267Glu, His268Phe, and serine 324 threonine (Ser324Thr) has been found to largely improve CDC at the expense of reduced ADCC and ADCP via increasing the affinity to inhibitory FcγRIIb, see entire document, Table 3, p. 186, right col.
But for the reasons noted, one cannot predict, a prior, which modifications will convey the desired functional activity.
There are insufficient working examples.
As such, it would require undue experimentation of one skilled in the art to practice the claimed invention. See page 1338, footnote 7 of Ex parte Aggarwal, 23 USPQ2d 1334 (PTO Bd. Pat App. & Inter. 1992).
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 4 and 30 are rejected under 35 U.S.C. 102 (a)(1)as being anticipated by US Patent No. 10,239,942 (issued March 26, 2019; PTO 892).
1. (Original) An agonist antibody to human PD-1 or a functional fragment thereof, wherein the antibody or a functional fragment thereof binds to domain #7 as shown in SEQ ID NO: 9, of human PD-1.
4. (Previously Presented) The antibody or a functional fragment thereof of claim 1, wherein the antibody variable region comprises the framework of human antibody or the framework of humanized antibody.
Regarding claim 1, the ‘942 patent teaches agonist (see col. 12, line 53-58) antibody or antigen binding fragment thereof that binds to epitope 61 of human PD-1, see entire document, col. 8, line 56-60, Table 5, peptide PD108, in particular. Examples of functional binding fragment include Fab, Fab’, F(ab’)2, Fv, single chain antibodies, (e.g., scFv), minibodies, and diabodies, see col. 6, lines 52-62, col. 9, line 9-65, in particular.
The reference SEQ ID NO: 61 is identical to the claimed SEQ ID NO: 9, see sequence alignment below:
Query Match 100.0%; Score 53; Length 15;
Best Local Similarity 100.0%;
Matches 11; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 SPALLVVTEGD 11
|||||||||||
Db 3 SPALLVVTEGD 13
Regarding claim 4, the ‘942 patent teaches that humanized antibody comprises antibody variable domain and human frameworks (FRs), see col. 11, line 22-55, in particular.
Regarding claim 30, the ‘942 patent teaches pharmaceutical composition comprising the reference antibody and a pharmaceutically acceptable excipient or physiological saline, see col. 18, lines 4-49, in particular.
Thus, the reference teachings anticipate the claimed invention.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1 and 5-9 are rejected under 35 U.S.C. 103 as being unpatentable over US Patent No. 10,239,942 (issued March 26, 2019; PTO 892) in view of Yachi et al (US20190270818, published September 5, 2019; PTO 892).
The teachings of the ‘942 patent have been discussed supra. The ‘942 patent reaches that the agonist anti-PD-1 antibodies are useful for treating various type of cancer, and the antibodies can be engineered, e.g., human antibody or humanized antibody to minimize or eliminate an immune response when administered to a human patient, see col. 6, lines 52-58, in particular.
The ‘942 patent does not teach the antibody or a functional fragment thereof of claim 1, wherein the antibody heavy chain constant region and the antibody light chain constant region comprise an amino acid sequence derived from human antibody as per claim 6, wherein the antibody heavy chain constant region is the antibody heavy chain constant region of human IgG as per claim 7, wherein the antibody heavy chain constant region of said human IgG is the antibody heavy chain constant region of human IgG1 as per claim 8 and wherein the antibody light chain constant region is the antibody light chain constant region of human Igκ as per claim 9.
However, Yachi teaches various agonist antibodies that bind to human PD-1 (see entire document, Examples 2, 3, 4, in particular) wherein the antibody is human IgG1 isotype as per claims 6-8 (see para. [0014], [0038]) and human kappa light chain constant CL as per claim 9 (see para. [0039], [0043], in particular). Yachi teaches that the Fc portion of human IgG1 isotype binds to the Fc-gamma receptor family that can induce antibody-dependent cell cytotoxicity (ADCC) as well as C1q that can induce complement-dependent cytotoxicity (CDC), see para. [0038]. The antibody inhibits human primary T cell proliferation (see Example 6), and does not induce significant cytokine release for IFNγ, IL-2, IL-6, IL-10 and TNF-α, see Example 7, in particular for treating Graft-Versus-Host Disease (GVHD), see Example 8 or Lupus Nephritis (Example 9).
In view of the combined teachings of the references, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filling date of the claimed invention to combine the teachings of the ‘942 patent and Yachi by producing agonist humanized or human antibody that binds to epitope SPALLVVTEGD of human PD-1 of the ‘942 patent with the Fc from human IgG1 and human kappa light chain constant of Yachi to arrive at the claimed invention with a reasonable expectation of success, e.g., binds to human Fcγ receptors and C1q for treating cancer or autoimmune diseases.
One of ordinary skill in the art would have been motivated to do so because the ‘942 patent teaches that humanized or human agonist anti-PD-1 antibody minimize or eliminate an immune response when administered to a human patient, see col. 6, lines 52-58, in particular.
One of ordinary skill in the art would have been motivated to do so because Yachi teaches that the agonist antibody that binds to human PD-1 does not induce cytokine storm (side effect, Example 7) and the Fc portion of human IgG1 isotype binds to the Fc-gamma receptor family that can induce antibody-dependent cell cytotoxicity (ADCC) as well as C1q that can induce complement-dependent cytotoxicity (CDC), see para. [0038].
“The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.”
In this case, using known technique would improve similar products in the same way. Applying known technique to a known product would improve the product with predictable results. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007).
“The test of obviousness is not express suggestion of the cl aimed invention in any or all of the references but rather what the references taken collectively would suggest to those of ordinary skill in the art presumed to be familiar with them.” See In re Rosselet 146 USPQ 183, 186 (CCPA 1965).
“There is no requirement (under 35 USC 103(a)) that the prior art contain an express suggestion to combine known elements to achieve the claimed invention. Rather, the suggestion to combine may come from the prior art, as filtered through the knowledge of one skilled in the art.,” Motorola, Inc, v. Interdigital Tech. Corn., 43 USPQ2d 1481, 1489 (Fed. Cir. 1997).
Accordingly, the claimed invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filling date of the claimed invention especially in the absence of evidence to the contrary.
Claims 10-11 and 17-20 are rejected under 35 U.S.C. 103 as being unpatentable over US Patent No. 10,239,942 (issued March 26, 2019; PTO 892) in view of Yachi et al (US20190270818, published September 5, 2019; PTO 892) as applied to claims 1 and 5-9 mentioned above and further in view of D'Angelo (US20130089541, published April 11, 2013; PTO 892), Sainson et al (US20180066058, published March 8, 2018; PTO 892) and Liu et al (US20200262894, published August 20, 2020; PTO 892) or Chen et al (WO2018226580, published December 13, 2018; PTO 892).
The combine teachings of the ‘942 patent and Yachi have been discussed supra.
The references do not teach that the antibody or a functional fragment thereof of claim 1, wherein the antibody or a functional fragment thereof has an improved affinity to any one or more of the following receptors: human FcγRIIA, human FcγRIIB or human FcγRIIA as per claim 10 or wherein the antibody or a functional fragment thereof has an improved affinity to human FcγRIIB as per claim 11 or wherein the antibody or a functional fragment thereof has an improved affinity to human FcyRIIIA as per claim 12, wherein the antibody or a functional fragment has a modified Fc region of human IgG1, and the affinity of the antibody or a functional fragment thereof to said receptor has been improved by modification of the Fc region of human IgG1 or wherein any of the amino acids at positions 233, 234, 236, 237, 238, 239, 267, 268, 271, 296, 323, 326, 328, 330 and 332 (according to EU numbering) in the amino acid sequence of the Fc region of human IgGl is modified as per claim 19 wherein the modification comprises S239D, S267G, H268D, see para. [0183].
However, D'Angelo teaches antibodies with enhanced or suppressed effector function.
Regarding claim 12, D'Angelo teaches that Fc mutation, e.g., S298A/K326A/A327H wherein the polypeptide has improved binding selectivity to Fc.gamma, see para. [0042]. One of the modifications comprises the mutation S239E wherein the polypeptide has higher selectivity in binding to the Fc.gamma.RIIIa receptor compared to a polypeptide that lacks the S239E mutation, see para. [0046].
Regarding claims 10, 11, 17, D'Angelo teaches that Fc mutation that synergistically provide desired selectivity and binding affinity for the target Fc receptor, e.g., favorable Fc.gamma.RIIb -specific interactions and/or unfavorable interactions with Fc.gamma.RIIIa (FcγRIIIa) and/or Fc.gamma.RIIa (FcγRIIa) receptors, see [0022], [0031].
Regarding claims 18, 19, D'Angelo teaches Fc variant of human IgG1 comprising one or more amino acid substitutions are located between positions 234-330 according to the EU index, see para. [0047], reference claims 1, 34.
Regarding claim 20, D'Angelo teaches one or more amino acid substitutions, e.g., S239D and H268D or S239D, S267G and H268D, numbering according to EU, see para. [0050], [0079]. Claims 35, 40.
D'Angelo does not teach amino acid substitution at position K322A as per claim 20.
Likewise, Sainson teaches human IgG heavy chain constant region may comprise one or more amino acid mutations that reduce the affinity of the IgG for human FcγRIIIA, human FcγRIIA, or human FcγRI but enhanced binding of human IgG to the FcγRIIB as the FcγRIIB is expressed on a cell selected from the group consisting of macrophages, monocytes, B-cells, dendritic cells, endothelial cells, and activated T-cells. In one embodiment, the variant human IgG heavy chain constant region comprises one or more of the following amino acid mutations G236A, S239D, Y300L, (EU index numbering system). In one embodiment, the variant human IgG heavy chain constant region comprises a set of amino acid mutations selected from the group consisting of: S239D; I332E; S239D and I332E; S239D, A330L, and I332E; G236A, S239D, and I332E (EU index numbering system). In one embodiment, the variant human IgG heavy chain constant region comprises a S239D, A330L, or I332E amino acid mutations (EU index numbering system). In one embodiment, the variant human IgG heavy chain constant region comprises an S239D and I332E amino acid mutations (EU index numbering system). In one embodiment, the variant human IgG heavy chain constant region is a variant human IgG1 heavy chain constant region comprising the S239D and I332E amino acid mutations (EU index numbering system). In one embodiment, the antibody or fragment comprises an afucosylated Fc region.
D'Angelo and Sainson do not teach K322A as per claim 20.
However, Liu teaches one or more mutations (e.g., substitutions) to modify (e.g., improve, reduce, or ablate) Fc functionalities include the S239D/A330L/I332E; S239D/I332E/G236A; K322A mutations, and these mutations are known in the art, see para. [0060].
The WO2018226580 publication teaches agonist anti-PD1 antibody (see entire document, p. 11) wherein the antibody is an IgG1 isotype (see p. 47) and wherein the Fc at position K322A substitution for reduce CDC, see p. 49, last line, in particular. Exemplary combination mutations that result in antibodies with reduced ADCC are shown on p. 49.
In view of the combined teachings of the references, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filling date of the claimed invention to produce the ‘942 patent and Yachi’s agonist human IgG1 antibody that binds to human PD-1 wherein the human Igg1 Fc is modified by one or more amino acids at positions 233, 234, 236, 237, 238, 239, 267, 268, 271, 296, 323, 326, 328, 330 and 332 (according to EU numbering) such as S239D and H268D or S239D, S267G and H268D as taught by D'Angelo or S239D; I332E; S239D and I332E; S239D, A330L, and I332E; G236A, S239D, and I332E (EU index numbering system) as taught by Sainson and S239D/A330L/I332E; S239D/I332E/G236A; K322A substitution as taught by Liu to arrive at the claimed S239D, S267G H268D and K322A with a reasonable expectation of success, e.g., increase affinity for human FcγIIB (aka CD32, an inhibitory receptor) and/or FcγRIIIA (aka CD16).
One of ordinary skill in the art would have been motivated to do so because Liu teaches that these one or more substitutions are known in the art and Sainson teaches these one or more S239D; I332E; S239D and I332E; S239D, A330L, and I332E; G236A, S239D, and I332E substitutions (EU index numbering system) in the human IgG heavy chain constant region binds to human Fcγ receptors selected from the group consisting of FcγRIIB and FcγRIIA with higher affinity than the wild type human Fcγ receptors, e.g., human FcγRIIIA, human FcγRIIA, or human FcγRI. see para. [0183].
One of ordinary skill in the art would have been motivated to combine D'Angelo’s S239D, S267G and H268D with Liu’s or Chen’s K322A because Liu teaches that the K322A mutation reduce, or ablate) Fc functionalities, and these mutations are known in the art (see para. [0060]) and D'Angelo teaches that S239D, S267G and H268D substitution may reduce the affinity for human FcγRIIIA, human FcγRIIA, or human FcγRI, see para. [0188].
One of ordinary skill in the art would have been motivated to do so because Sainson teaches that antibody may promote anti-tumor response with a low risk of undesirable activation of a wider T cell response that could cause treatment-limiting autoimmune adverse events, see para. [0588].
One of ordinary skill in the art would have been motivated to do so because Chen teaches that K322A mutation reduces complement mediated cytotoxicity (CDC), see p. 49.
“The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007).
“The test of obviousness is not express suggestion of the cl aimed invention in any or all of the references but rather what the references taken collectively would suggest to those of ordinary skill in the art presumed to be familiar with them.” See In re Rosselet 146 USPQ 183, 186 (CCPA 1965).
“There is no requirement (under 35 USC 103(a)) that the prior art contain an express suggestion to combine known elements to achieve the claimed invention. Rather, the suggestion to combine may come from the prior art, as filtered through the knowledge of one skilled in the art.,” Motorola, Inc, v. Interdigital Tech. Corn., 43 USPQ2d 1481, 1489 (Fed. Cir. 1997).
Accordingly, the claimed invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filling date of the claimed invention especially in the absence of evidence to the contrary.
Claim 24 is rejected under 35 U.S.C. 103 as being unpatentable over US Patent No. 10,239,942 (issued March 26, 2019; PTO 892) in view of Yachi et al (US20190270818, published September 5, 2019; PTO 892) as applied to claims 1 and 5-9 mentioned above and further in view of Shields et al (J Biol Chemistry 277(30): 26733-26740, 2002; PTO 892).
The combine teachings of the ‘942 patent and Yachi have been discussed supra.
The references do not teach that the antibody or a functional fragment thereof of claim 1, wherein the antibody or a functional fragment thereof is defucosylated as per claim 24.
However, Shields teaches lack of fucose on human IgG1 N-linked oligosaccharide improves binding to human Fc.gamma.RIII (see entire document, p. 26735, left col. Table II, p. 26737, right col., in particular) and antibody-dependent Cellular toxicity (ADCC, p. 26738, Fig. 6, p. 26739, left col, in particular. Shields teaches that the fucose-deficient IgG1 antibody can be produced in Lec13 cells as opposed to in CHO cells, see p. 26734, left col., Experimental Procedures, p. 26739, in particular.
In view of the combined teachings of the references, it would have been prima facie obvious to a person of ordinary skill in the art before the effective filling date of the claimed invention to produce defucosylated agonist anti-PD-1 antibody of the ‘942 patent and Yachi using the Lec13 cells as taught by Shields in order to enhanced the binding of human IgG1 agonist antibody to human FcγRIIIa.
One of ordinary skill in the art would have been motivated to do so because Shields teaches that the lack of fucose on human IgG1 improves binding of human IgG1 agonist antibody to human FcγRIIIa, and improved antibody-dependent Cellular toxicity (ADCC).
In this case, using known technique would improve similar products in the same way. Applying known technique to a known product would improve the product with predictable results. KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007).
“The test of obviousness is not express suggestion of the cl aimed invention in any or all of the references but rather what the references taken collectively would suggest to those of ordinary skill in the art presumed to be familiar with them.” See In re Rosselet 146 USPQ 183, 186 (CCPA 1965).
“There is no requirement (under 35 USC 103(a)) that the prior art contain an express suggestion to combine known elements to achieve the claimed invention. Rather, the suggestion to combine may come from the prior art, as filtered through the knowledge of one skilled in the art.,” Motorola, Inc, v. Interdigital Tech. Corn., 43 USPQ2d 1481, 1489 (Fed. Cir. 1997).
Accordingly, the claimed invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filling date of the claimed invention especially in the absence of evidence to the contrary.
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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-5, 19, and 30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6, 11-17, 28 of copending Application No. 17/923,996 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims overlap in scope with the copending ‘996 application.
The claims of copending application are directed to both a pharmaceutical composition comprising a PD-1 agonist, wherein the PD-1 agonist comprises an anti-PD-1 agonist antibody or a functional fragment thereof (genus, claim 15), or wherein the PD-1 agonist comprises an anti-human PD-1 monoclonal antibody selected from the group consisting of MIH4, J116, MH266, HM647 and HM698, wherein the anti-PD-1 agonist antibody or a functional fragment thereof binds to a domain #7 of a PD-1, wherein the domain #7 corresponds to amino acid positions 38 to 48 in an amino acid sequence of SEQ ID NO: 24 and a method for preventing and/or treating Th2-mediaetd disease.
The reference agonist PD-1 antibody HM266 is the same agonist antibody HM266 for treating inflammatory autoimmune disease of instant application. The reference HM266 antibody (claim 16) binds to a domain 7 of a PD-1 wherein the domain #7 corresponds to amino acid position 38 to 48 of SEQ ID NO: 24 (SPALLVVTEGD), which corresponds to instant domain 7 as shown in SEQ ID NO: 9 (SPALLVVTEGD) recited in instant claim 1.
The reference agonist PD-1 antibody HM266 comprises the same heavy and light chains CDRs as instant AbHM266 (instant claim 3 (B)).
Ab HM266
18/290,006
17/923,996
SEQ ID NO: 350
SYYIQ
SYYIQ
SEQ ID NO: 352
WIYPGDGSSKYNEKFKG
WIYPGDGSSKYNEKFKG
SEQ ID NO: 353
YYGSSFDY
YYGSSFDY
SEQ ID NO: 354
RASQDISNYLN
RASQDISNYLN
SEQ ID NO: 355
YSSRLHS
YSSRLHS
SEQ ID NO: 356
QQGSTLPFT
QQGSTLPFT
A person of skill in the art, reading the claims of the ‘996 application, would look to the application and follow the ‘996 application’s express instruction on how to make the product within the reference, e.g., p. 11, HM266, having one or more substitution at 236, 268, 239, 328, 332, 233, 237, 238, 271, 330, 267, 326, 323, and 296 (see p. 14), thereby arriving at the agonist antibody to human PD-1 of the examined claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Allowable Subject Matter
Claims 2, 3, 5 and 23 are free of prior art.
Conclusion
No claim is allowed.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Misook Yu, can be reached at 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PHUONG HUYNH/ Primary Examiner, Art Unit 1641
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