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 1-3, 6-7, 9-12, 14 and 15 are pending.
Applicant’s election without traverse of Group I that read on (A) positions 236, 311, 396 and 428 and (B) wherein that substitutions are G236A, Q311R, P396L and M428L as the species of combination of amino acid substitutions in the reply filed on September 28, 2026 is acknowledged.
Claims 12, 14 and 15 are withdrawn from further consideration by the examiner, 37 C.F.R. 1.142(b) as being drawn to non-elected inventions.
Claims 1-3, 6-7 and 9-11, drawn to a human antibody Fc that read on (A) , 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 April 10, 2026, September 12, 2025 and April 17, 2024 have been considered by the examiner and an initialed copy of the IDS is included with this Office Action.
Drawings
The drawings filed on April 17, 2024 are acceptable.
Abstract
The abstract of the disclosure is objected to because it exceeds 150 words. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
Specification
The amendment to the specification filed on April 17, 2024 has been entered.
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 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 1-3, 6-7 and 9-11 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.
Claim 2 recites “…C229R, A231V, G236A, K236W, F243L, Q311R, R355L, P396L, and M428L” and claim 2 depends from claim 1 which recites “numbered according to a Kabat numbering system” is indefinite because when numbering according to EU index of Kabat, position 229 is a C (cysteine, see dependent claims 2-3), but the corresponding numbering in Kabat is 242, not C229, see arrow in chart below.
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The same numbering system issue applies to positions 231, 236, 243, 311, 355, 396 and 428.
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Accordingly, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Claims 1, 3, 6-7 and 9-11 are included in the rejection because they are dependent on rejected claim and do not correct the deficiency of the claim from which they depend.
Note, amending claim 1 to recite “EU index of Kabat” would obviate this rejection, see specification p. 15.
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 1-3, 6-7 and 9-11 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.
The Written Description Guidelines for examination of patent applications indicates, “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 characteristics and/or other 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 applicant was in possession of the claimed genus.” (see MPEP 2163).
Claim 1 encompasses any human antibody Fc domain variant in which one or more amino acids selected from the group consisting of amino acids at positions 229, 231, 236, 243, 311, 355, 396 and 428 numbered according to a Kabat numbering system in a wide-type human antibody Fc domain are substituted with sequences different from wild-type amino acids.
Claim 2 encompasses the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant comprises one or more amino acid substitutions selected from the group consisting of C229R, A231V, G236A, G236W, F243L, Q311R, R355L, P396L, and M428L.
Claim 3 encompasses the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant comprises amino acid substitutions of G236A, Q311R, P396L and M428L (elected species): C229R, G236A, Q311R, P396L and M428L: or A231V, G236W, F243L, Q311R, R355L, P396L and M428L.
Claim 6 encompasses the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant has enhanced binding capacity to FcγRIIα and enhanced ability to induce antibody dependent cellular phagocytosis (ADCP)compared to wild-type human antibody Fc domains.
Claim 7 encompasses the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant has an enhanced selective binding capacity to human FcγRIIα compared to human FcγRIIβ.
Claim 9 encompasses the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant exhibits low binding affinity to FcRn at pH 7.0 to 7.8 compared to the wild-type human antibody Fc domain.
Claim 10 encompasses the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant exhibits high binding affinity to FcRn at pH 5.6 to 6.5 compared to the wild-type human antibody Fc domain.
Claim 11 encompasses the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant has increased in vivo half-life compared to the wild-type human antibody Fc domain.
The specification discloses just human IgG1 Fc variants comprising the amino acid sequence of SEQ ID NO: 1, 3 or 5, see specification at p. 12. The human IgG1 Fc variant WHFc1 comprises the amino acid sequence of SEQ ID NO: 1 having substitutions of G236A, Q311R, P396L and M428L, numbered according to EU index of Kabat. The human IgG1 Fc variant WHFc2 comprises the amino acid sequence of SEQ ID NO: 2 having C229R, G236A, Q311R, P396L and M428L substitution. The human IgG1 Fc variant WHFc5 comprising the amino acid sequence of SEQ ID NO: 5 having A231V, G236W, F243L, Q311R, R355L, P396L and M428L substitutions, numbering according to EU index of Kabat, see p. 12, 15, Table 1 below:
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However, the specification does not describe any human antibody Fc domain variant in which one or more amino acids at positions 239, 231, 236, 243, 311, 355, 396, and/or 428 substituted with any “sequences”, numbering according to Kabat numbering system (claim 1). The specification does not describe the structure, e.g., amino acid sequences to be substituted at any one of the positions, numbering according to Kabat numbering system above or EU numbering of Kabat.
Even assuming the substitutions are amino acid, the term substitution encompasses conservative and non-conservative substitutions. It is unpredictable which amino acid substitutions at any one or more positions 239, 231, 236, 243, 311, 355, 396, and/or 428 enhanced FcγRIIα binding (claims 6, 7), improved ADCP (claim 6), low binding affinity to FcRn at pH 7.0 to 7.8 compared to wild-type human antibody Fc domain (claim 9), high binding affinity to FcRn at pH 5.6 to 6.5 (claim 10), and/or increased in vivo half-life compared to the wild-type human antibody Fc domain (claim 11).
Even assuming the substitutions are the ones recited in claims 2 and 3, position 229 in human IgG3 hinge according to Kabat numbering is T, NOT C.
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Likewise, position 229 in IgG4 hinge according to Kabat numbering is Y, not C.
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The same issue applies to positions 239, 231, 236, 243, 311, 355, 396, and/or 428.
The specification does not provide a representative number of species human antibody Fc domain variants to describe the claimed genus; the specification does not describe the common structure share by member of the genus having the particular functions in claims 6-7, 9-11.
The state of the art at the time the invention was made recognized that even single amino acid differences can result in drastically altered function of antibodies.
For example, Lund et al. (The Journal of Immunology 157:4963-4969, 1996; PTO 892) show that even a single amino acid replacement within the CH2 domain of IgG can alter the glycosylation profile of an antibody therefore influence its effector functions of Fc receptor binding and complement activation (see entire document, particularly Discussion on pages 4966-4968).
Lazar et al. (WO03/074679; PTO 892) teach that the determinants of antibody properties, such as stability, solubility and affinity for antigen, important to its functions are overlapping; thus engineering an antibody to be more soluble may cause a loss in affinity for its antigen (see entire document, particularly page 3).
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 the prior art teaches that random substitution is not a certainty, and is necessarily determined empirically.
Since the disclosure fails to describe common attributes or characteristics that identify members of the genus, and because the genus is highly variant, the disclosure is insufficient to describe the genus. Thus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus as broadly claimed.
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 isolated human IgG1 Fc domain variant comprises amino acid substitutions G236A, Q311R, P396L and M428L; C229R, G236A, Q311R, P396L and M428L; or A231V, G236W, F243L, Q311R, R355L, P396L and M428L, numbered according to EU index of Kabat, (2) the isolated human IgG1 Fc domain variant comprises the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 3 or SEQ ID NO: 5, (3) the isolated human IgG1 Fc domain variant above wherein the human antibody Fc domain variant has enhanced binding capacity to FcγRIIα and enhanced ability to induce antibody dependent cellular phagocytosis (ADCP) compared to wild-type human antibody Fc domains, 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 1-3, 6-7 and 9-11 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 isolated human IgG1 Fc domain variant comprises amino acid substitutions G236A, Q311R, P396L and M428L; C229R, G236A, Q311R, P396L and M428L; or A231V, G236W, F243L, Q311R, R355L, P396L and M428L, numbered according to EU index of Kabat, (2) the isolated human IgG1 Fc domain variant comprises the amino acid sequence of SEQ ID NO: 1, SEQ ID NO: 3 or SEQ ID NO: 5, (3) the isolated human IgG1 Fc domain variant above wherein the human antibody Fc domain variant has enhanced binding capacity to FcγRIIα and enhanced ability to induce antibody dependent cellular phagocytosis (ADCP) compared to wild-type human antibody Fc domains, does not reasonably provide enablement for any human antibody Fc domain variants as set forth in claims 1-3, 6-7 and 9-11. 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 human antibody Fc domain variant in which one or more amino acids selected from the group consisting of amino acids at positions 229, 231, 236, 243, 311, 355, 396 and 428 numbered according to a Kabat numbering system in a wide-type human antibody Fc domain are substituted with sequences different from wild-type amino acids.
Claim 2 encompasses the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant comprises one or more amino acid substitutions selected from the group consisting of C229R, A231V, G236A, G236W, F243L, Q311R, R355L, P396L, and M428L.
Claim 3 encompasses the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant comprises amino acid substitutions of G236A, Q311R, P396L and M428L (elected species): C229R, G236A, Q311R, P396L and M428L: or A231V, G236W, F243L, Q311R, R355L, P396L and M428L.
Claim 6 encompasses the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant has enhanced binding capacity to FcγRIIα and enhanced ability to induce antibody dependent cellular phagocytosis (ADCP)compared to wild-type human antibody Fc domains.
Claim 7 encompasses the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant has an enhanced selective binding capacity to human FcγRIIα compared to human FcγRIIβ.
Claim 9 encompasses the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant exhibits low binding affinity to FcRn at pH 7.0 to 7.8 compared to the wild-type human antibody Fc domain.
Claim 10 encompasses the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant exhibits high binding affinity to FcRn at pH 5.6 to 6.5 compared to the wild-type human antibody Fc domain.
Claim 11 encompasses the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant has increased in vivo half-life compared to the wild-type human antibody Fc domain.
The specification discloses just human IgG1 Fc variants comprising the amino acid sequence of SEQ ID NO: 1, 3 and 5, see specification at p. 12. The human IgG1 Fc variant WHFc1 comprises the amino acid sequence of SEQ ID NO: 1 having substitutions of G236A, Q311R, P396L and M428L. The human IgG1 Fc variant WHFc2 comprises the amino acid sequence of SEQ ID NO: 2 having C229R, G236A, Q311R, P396L and M428L substitution. The human IgG1 Fc variant WHFc5 comprising the amino acid sequence of SEQ ID NO: 5 having A231V, G236W, F243L, Q311R, R355L, P396L and M428L substitutions, numbering according to EU index of Kabat, see p. 12, 15, Table 1 below:
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However, the specification does not teach any human antibody Fc domain variant in which one or more amino acids at positions 239, 231, 236, 243, 311, 355, 396, and/or 428 substituted with any “sequences”, numbering according to Kabat numbering system (claim 1). The specification does not teach the structure, e.g., amino acid sequences to be substituted at any one of the positions, numbering according to Kabat numbering system above or EU numbering of Kabat.
Even assuming the substitutions are amino acid, the term substitution encompasses conservative and non-conservative substitutions. There are insufficient working examples. It is unpredictable which amino acid substitutions at one or more positions 239, 231, 236, 243, 311, 355, 396, and/or 428 enhanced FcγRIIα binding (claims 6, 7), improved ADCP (claim 6), low binding affinity to FcRn at pH 7.0 to 7.8 compared to wild-type human antibody Fc domain (claim 9), high binding affinity to FcRn at pH 5.6 to 6.5 (claim 10), and/or increased in vivo half-life compared to the wild-type human antibody Fc domain (claim 11). Even assuming the substitutions are the ones recited in claims 2 and 3, it should be noted that position 229 in human IgG3 hinge according to Kabat numbering is T, NOT C.
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Likewise, position 229 in IgG4 hinge according to Kabat numbering is Y, not C.
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The same issue applies to positions 239, 231, 236, 243, 311, 355, 396, and/or 428.
The state of the art at the time the invention was made recognized that even single amino acid differences can result in drastically altered function of antibodies.
For example, Lund et al. (The Journal of Immunology 157:4963-4969, 1996; PTO 892) show that even a single amino acid replacement within the CH2 domain of IgG can alter the glycosylation profile of an antibody therefore influence its effector functions of Fc receptor binding and complement activation (see entire document, particularly Discussion on pages 4966-4968).
Lazar et al. (WO 03/074679; PTO 892) teach that the determinants of antibody properties, such as stability, solubility and affinity for antigen, important to its functions are overlapping; thus engineering an antibody to be more soluble may cause a loss in affinity for its antigen (see entire document, particularly page 3).
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 the prior art teaches that random substitution is not a certainty, and is necessarily determined empirically.
There are insufficient working examples. It is unpredictable which human Fc variants having any one or more substitutions at positions 239, 231, 236, 243, 311, 355, 396, and/or 428 enhanced FcγRIIα binding (claims 6, 7), improved ADCP (claim 6), low binding affinity to FcRn at pH 7.0 to 7.8 compared to wild-type human antibody Fc domain (claim 9), high binding affinity to FcRn at pH 5.6 to 6.5 (claim 10), and/or increased in vivo half-life compared to the wild-type human antibody Fc domain (claim 11).
As such, one skilled in the art cannot practice the invention with a reasonable expectation of success without undue experimentation.
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 1-2, 6 and 7 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Georgiou (US20140179550, published June 26, 2014; PTO 1449).
Claim interpretation:
Claim 1 recites a human antibody Fc domain variant in which one or more amino acids selected from the group consisting of amino acids at positions 229, 231, 236, 243, 311, 355, 396 and 428 numbered according to EU numbering of Kabat in a wide-type human antibody Fc domain are substituted with sequences different from wild-type amino acids.
Claim 2 recites the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant comprises one or more amino acid substitutions selected from the group consisting of C229R, and M428L.
Claim 6 encompasses the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant has enhanced binding capacity to FcγRIIα and enhanced ability to induce antibody dependent cellular phagocytosis (ADCP)compared to wild-type human antibody Fc domains.
Claim 7 encompasses the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant has an enhanced selective binding capacity to human FcγRIIα compared to human FcγRIIβ.
Georgiou teaches human antibody Fc domain (see para. [0015]) comprises one or more amino acid substitution, e.g., C229R, E382, M428L, wherein the numbering of the residues is that of the EU index as in Kabat, (see para. [0194], Example 8, [0025], [0354], in particular). The term “comprising” is open ended. It expands the substitutions to include additional ones.
Since the prior art product is the same as that of claims 1-2, its properties, e.g., enhanced binding to FcγRIIa and enhanced ability to induce antibody dependent cellular phagocytosis (ADCP) compared to wild-type human Fc domain (claim 6) and enhance selective binding to human FcγRIIa compared to human FcγRIIb (claim 7) must necessarily be present; see MPEP 2112.01(I) and (II). Since the Patent Office does not have the facilities for examining and comparing the human IgG Fc variant of the instant invention to those of the prior art, the burden is upon the applicant to prove that the product to which the claims are directed is different than that taught by the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430(CCPA 1977).
Thus, the reference teachings anticipate the claimed invention.
Claims 1-2, 6 and 7 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Lazar (US20060134105, published June 22, 2006; PTO 892).
Claim interpretation:
Claim 1 recites a human antibody Fc domain variant in which one or more amino acids selected from the group consisting of amino acids at positions 229, 231, 236, 243, 311, 355, 396 and 428 numbered according to EU numbering of Kabat in a wide-type human antibody Fc domain are substituted with sequences different from wild-type amino acids.
Claim 2 recites the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant comprises one or more amino acid substitutions selected from the group consisting of G236A.
Claim 6 encompasses the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant has enhanced binding capacity to FcγRIIα and enhanced ability to induce antibody dependent cellular phagocytosis (ADCP)compared to wild-type human antibody Fc domains.
Claim 7 encompasses the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant has an enhanced selective binding capacity to human FcγRIIα compared to human FcγRIIβ.
Lazar teaches human IgG1 Fc variant (see para. [0012]) comprising G236A substitution wherein the numbering of the residues is that of the EU index as in Kabat, (see caption of Fig. 6, 7, in particular).
The term “comprising” is open ended. It expands the substitutions to include additional ones.
Since the prior art product is the same as that of claims 1-2, its properties enhanced binding to FcγRIIa and enhanced ability to induce antibody dependent cellular phagocytosis (ADCP) compared to wild-type human Fc domain (claim 6) and enhance selective binding to human FcγRIIa compared to human FcγRIIb (claim 7) must necessarily be present; see MPEP 2112.01(I) and (II). Since the Patent Office does not have the facilities for examining and comparing the human IgG Fc variant of the instant invention to those of the prior art, the burden is upon the applicant to prove that the product to which the claims are directed is different than that taught by the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430(CCPA 1977).
Thus, the reference teachings anticipate the claimed invention.
Claims 1-2, 6 and 7 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Guler-Gane (US20100184959, published July 22, 2010; PTO 892).
Claim interpretation:
Claim 1 recites a human antibody Fc domain variant in which one or more amino acids selected from the group consisting of amino acids at positions 229, 231, 236, 243, 311, 355, 396 and 428 numbered according to EU numbering of Kabat in a wide-type human antibody Fc domain are substituted with sequences different from wild-type amino acids.
Claim 2 recites the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant comprises one or more amino acid substitutions selected from the group consisting of F243L and Q311R.
Guler-Gane teaches human IgG1 Fc variant (see para. para. [0061], reference SEQ ID NO: 1) comprising 243S or 243L, or 311R (see para. [0047]), Q311R substitution (see para. [0050], SEQ ID NO: 20) wherein the numbering of the residues is that of the EU index as in Kabat, see para. [0047], [0051], in particular. Guler-Gane teaches Fc polypeptide variant having a mutation at two or more position, such as 243S/L/G/H/I, 311R, 355W, 428T, see para. [0053], reference claims 35, 71, 81.
The reference substitutions have enhanced recognition for FcγRIIa, see [0012].
The term “comprising” is open ended. It expands the substitutions to include additional ones.
Since the prior art product is the same as that of claims 1-2, its properties enhanced binding to FcγRIIa and enhanced ability to induce antibody dependent cellular phagocytosis (ADCP) compared to wild-type human Fc domain (claim 6) and enhance selective binding to human FcγRIIa compared to human FcγRIIb (claim 7) must necessarily be present; see MPEP 2112.01(I) and (II). Since the Patent Office does not have the facilities for examining and comparing the human IgG Fc variant of the instant invention to those of the prior art, the burden is upon the applicant to prove that the product to which the claims are directed is different than that taught by the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430(CCPA 1977).
Thus, the reference teachings anticipate the claimed invention.
Claims 1-2, 6-7, and 11 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Wang (US20150353637, published Dec 10, 2015; PTO 892).
Claim interpretation:
Claim 1 recites a human antibody Fc domain variant in which one or more amino acids selected from the group consisting of amino acids at positions 229, 231, 236, 243, 311, 355, 396 and 428 numbered according to EU numbering of Kabat in a wide-type human antibody Fc domain are substituted with sequences different from wild-type amino acids.
Claim 2 recites the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant comprises one or more amino acid substitutions selected from the group consisting of P396L and M428L.
Claim 11 encompasses the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant has increased in vivo half-life compared to the wild-type human antibody Fc domain.
Wang teaches human IgG1 Fc variant (see para. [0249], [0250], [0255], [0256], [0257], [0571]) wherein the Fc may be modified, e.g., substitution (para. [0589]) to increase antibody dependent cellular cytotoxicity and/or increase the affinity for an Fcγ receptor by modifying one or more amino acids at positions such as 236E, 243V, 355, see para. [0587] to [0588], in particular.
Regarding claims 1, 6, Wang teaches that the Fc with enhanced binding to one or more activating Fc receptor, e.g., FcγRIIa, see para. [0575], in particular. Wang teaches that the Fc region may be modified, e.g., substitution (para. [0589]) to increase antibody dependent cellular cytotoxicity (ADCC) and/or increase the affinity for an Fcγ receptor by modifying one or more amino acids at positions such as 236E, 243V, 355, see para. [0587] to [0588], in particular.
Regarding claims 1, 2, 3, 11, Wang teaches that the Fc region may be substitute to increase binding to FcRn (aka increased in vivo half-life) by substituting at one or more positions, e.g., 428L, see para. [0593], [0594], in particular.
The term “comprising” is open ended. It expands the substitutions to include additional ones.
Since the prior art product is the same as that of claim 1, its properties enhanced binding to FcγRIIa and enhanced ability to induce antibody dependent cellular phagocytosis (ADCP) compared to wild-type human Fc domain (claim 6) and enhance selective binding to human FcγRIIa compared to human FcγRIIb (claim 7) must necessarily be present; see MPEP 2112.01(I) and (II). Since the Patent Office does not have the facilities for examining and comparing the human IgG Fc variant of the instant invention to those of the prior art, the burden is upon the applicant to prove that the product to which the claims are directed is different than that taught by the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430(CCPA 1977).
Thus, the reference teachings anticipate the claimed invention.
Claims 1, 6 and 7 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Igawa (US20140363428, published Dec 11, 2014; PTO 892).
Claim interpretation:
Claim 1 recites a human antibody Fc domain variant in which one or more amino acids selected from the group consisting of amino acids at positions 229, 231, 236, 243, 311, 355, 396 and 428 numbered according to EU numbering of Kabat in a wide-type human antibody Fc domain are substituted with sequences different from wild-type amino acids.
Regarding claim 1, Igawa teaches FcRn binding domain, e.g., human IgG1 (see para. [0181]) Fc variant comprising substitutions at one or more positions selected from the group consisting of 311 numbering according to EU index of Kabat (EU311, an alanine (A, Table 1, para. [0203]. [0253]), EU428 such as isoleucine (M428I, Table 1, para. [0253], see para. [0020], [56], [0188], [0286], [0361], in particular) or IgG1-C226S/C229S, see para. [0255], [0257] or EU236 (para. [0286]), all positions numbered by EU numbering (claims 65, 110).
The term “comprising” is open ended. It expands the substitutions to include additional ones.
Since the prior art product is the same as that of claim 1, its properties enhanced binding to FcγRIIa and enhanced ability to induce antibody dependent cellular phagocytosis (ADCP) compared to wild-type human Fc domain (claim 6) and enhance selective binding to human FcγRIIa compared to human FcγRIIb (claim 7) must necessarily be present; see MPEP 2112.01(I) and (II). Since the Patent Office does not have the facilities for examining and comparing the human IgG Fc variant of the instant invention to those of the prior art, the burden is upon the applicant to prove that the product to which the claims are directed is different than that taught by the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430(CCPA 1977).
Thus, the reference teachings anticipate the claimed invention.
Claims 1-2, 6-7 and 11 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Griffin (US20170029505, published February 2, 2017; PTO 892).
Claim interpretation:
Claim 1 recites a human antibody Fc domain variant in which one or more amino acids selected from the group consisting of amino acids at positions 229, 231, 236, 243, 311, 355, 396 and 428 numbered according to EU numbering of Kabat in a wide-type human antibody Fc domain are substituted with sequences different from wild-type amino acids.
Claim 2 recites the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant comprises one or more amino acid substitutions selected from the group consisting of P396L and M428L.
Claim 11 encompasses the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant has increased in vivo half-life compared to the wild-type human antibody Fc domain.
Regarding claims 1-2 and 11, Griffin teaches human IgG Fc domain is mutated by substituting the glutamine residue at position 311 with an arginine residue (Q311R), see para. [0102].
Griffin teaches human IgG Fc domain is mutated by substituting the methionine residue at position 428 with a leucine residue (M428L), see para. [0103].
Griffin teaches the Fc comprises one or more mutations which increase its binding to FcRn, such as Q311R, M428L, reference claims 10, 11, in particular. All positions are numbering according to the EU numbering system (see para. [0017]).
The term “comprising” is open ended. It expands the substitutions to include additional ones.
Since the prior art product is the same as that of claims 1-2, its properties enhanced binding to FcγRIIa and enhanced ability to induce antibody dependent cellular phagocytosis (ADCP) compared to wild-type human Fc domain (claim 6) and enhance selective binding to human FcγRIIa compared to human FcγRIIb (claim 7), increased in vivo half-life compared to wild-type human antibody Fc domain (claim 11) must necessarily be present; see MPEP 2112.01(I) and (II). Since the Patent Office does not have the facilities for examining and comparing the human IgG Fc variant of the instant invention to those of the prior art, the burden is upon the applicant to prove that the product to which the claims are directed is different than that taught by the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430(CCPA 1977).
Thus, the reference teachings anticipate the claimed invention.
Claims 1-2, 6-7, and 9-11 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Jung (US20200223938, published July 16, 2020; PTO 892).
Claim interpretation:
Claim 1 recites a human antibody Fc domain variant in which one or more amino acids selected from the group consisting of amino acids at positions 229, 231, 236, 243, 311, 355, 396 and 428 numbered according to EU numbering of Kabat in a wide-type human antibody Fc domain are substituted with sequences different from wild-type amino acids.
Claim 2 recites the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant comprises one or more amino acid substitutions selected from the group consisting of P396L and M428L.
Claim 11 encompasses the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant has increased in vivo half-life compared to the wild-type human antibody Fc domain.
Regarding claim 1, Jung teaches human IgG (see para. [0023]) Fc variants produced by substituting a portion of the amino acid sequence of the Fc domain of a human antibody with a different amino acid sequence, see para. [0019]. Jung teaches substituted Fc variant includes, as an amino acid substitution, M428L according to the Kabat EU numbering system, see para. [0026].
Regarding claim 2, Jung teaches the substituted Fc variant, e.g., PFc29 (SEQ ID NO: 31) includes, as amino acid substitutions, a) M428L and b) Q311R or L309G according to the Kabat EU numbering system, see para. [0027], [0053], Table 2, reference claim 1, in particular. The half-life of the Fc domain or the polypeptide including the Fc domain can be maximized by optimization of the corresponding antibody Fc regions, for example, M428L and Q311, see para. [0053]. The amino acid residues of the antibody Fc domain are designated according to the Kabat EU numbering system, see para. [0025]. The substituted Fc variant has a long half-life compared to the wild type, see para. [0046].
Regarding claim 9, Jung teaches that the variant PFc29 exhibits low binding affinity to FcRn at pH 7.4, which is between the claimed pH 7.0 to 7.8 compared to wild type (WT), see FIG. 12d, FIG. 13b, para. [0114], in particular.
Regarding claim 10, Jung teaches that the variant PFc29 exhibits affinity to FcRn at pH 5.8, which is between the claimed pH 5.6 to 6.5 compared to wild type (WT), see FIG. 12c, para. [0114], in particular.
Regarding claim 11, Jung teaches that the variant PFc29 exhibits increase in vivo half-life, see FIG. 15b, in particular.
Since the prior art product is the same as that of claims 1-2, its properties enhanced binding to FcγRIIa and enhanced ability to induce antibody dependent cellular phagocytosis (ADCP) compared to wild-type human Fc domain (claim 6) and enhance selective binding to human FcγRIIa compared to human FcγRIIb (claim 7) must necessarily be present; see MPEP 2112.01(I) and (II). Since the Patent Office does not have the facilities for examining and comparing the human IgG Fc variant of the instant invention to those of the prior art, the burden is upon the applicant to prove that the product to which the claims are directed is different than that taught by the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430(CCPA 1977).
Thus, the reference teachings anticipate the claimed invention.
Claims 1-2, 6-7 and 11 are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Lazar (US2020110021755, published January 27, 2011; PTO 892).
Claim interpretation:
Claim 1 recites a human antibody Fc domain variant in which one or more amino acids selected from the group consisting of amino acids at positions 229, 231, 236, 243, 311, 355, 396 and 428 numbered according to EU numbering of Kabat in a wide-type human antibody Fc domain are substituted with sequences different from wild-type amino acids.
Claim 2 recites the human antibody Fc domain variant of claim 1, wherein the human antibody Fc domain variant comprises one or more amino acid substitutions selected from the group consisting of G236A, G236W, F243L and M428L.
Regarding claim 1, Lazar teaches antibody Fc domain variant (para. [0006]) comprises at least one amino acid substitution at position selected from the group consisting of 231, 236, 243, wherein the numbering of the residues in the Fc region is that of the EU index as in Kabat, see entire document, para. [0020], in particular.
Regarding claim 2, Lazar teaches antibody Fc domain variant comprises at least one substitution selected from the group consisting of G236A, G236W, F243L and M428L, see para. [0020], in particular. Lazar further teaches P396L, M428L, see para. [0147], in particular.
Regarding claim 10, Lazar teaches that those modification improved binding at lower pH relative to the higher pH, see para. [0150].
Regarding claim 11, Lazar teaches that the engineered human IgG antibodies with longer serum half-lives, see para. [0150].
Since the prior art product is the same as that of claims 1-2, its properties enhanced binding to FcγRIIa and enhanced ability to induce antibody dependent cellular phagocytosis (ADCP) compared to wild-type human Fc domain (claim 6) and enhance selective binding to human FcγRIIa compared to human FcγRIIb (claim 7) must necessarily be present; see MPEP 2112.01(I) and (II). Since the Patent Office does not have the facilities for examining and comparing the human IgG Fc variant of the instant invention to those of the prior art, the burden is upon the applicant to prove that the product to which the claims are directed is different than that taught by the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430(CCPA 1977).
Thus, the reference teachings anticipate the claimed invention.
Conclusion
The combination of substitutions in Claim 3 are free of prior art.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PHUONG HUYNH whose telephone number is (571)272-0846. The examiner can normally be reached on 9:00 a.m. to 6:30 p.m. The examiner can also be reached on alternate alternative Friday from 9:00 a.m. to 5:30 p.m.
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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