DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s amendment, filed 06/10/2024, has been entered.
Claims 1, 4, 6, 9, 14, 16-17, 19-22, 24, 27-30, 34-35, 41-44 are pending and currently under examination.
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.
Claims 4 and 17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 4 recites the broad recitation “FcRn binding fragment comprises R, K, D or E at position 354”, and the claim also recites “optionally D or E” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 17 recites “at least one, such as one or two, antigen binding domains.” The phrase “such as” renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention.
Therefore, the claims are indefinite.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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, 6, 9, 17, 19-22, 28-30, 34, 42 and 43 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Shan et al. (PLOS One August 2016 e0160345; see entire document; cited in IDS).
Regarding claim 1, Shan discloses an IgG4 antibody that reads on a polypeptide comprising an FcRn binding fragment of an Fc region. Shan discloses the generation of monomeric Fc variants by mutagenesis of positions 351, 354, 366, 395, 405 and 407 of the Fc region followed by FcRn-based selection (Figure 2A; Materials and Methods, “Library Construction and Selection”). Shan further discloses the selected C4 Fc variant having the amino acid substitutions L351F, S354L, T366R, P395K, F405R and Y407E (Figure 3; Results section describing clone C4). Thus, Shan teaches an FcRn binding fragment comprising F at position 351, L at position 354, R at position 366, K at position 395, R at position 405 and E at position 407.
Regarding claim 6, given that Shan discloses that the monomeric Fc fragment corresponds to the Fc portion of a human IgG encompassing CH2 and CH3 domains, it would comprise about residue 216 to about residue 446 of an IgG molecule (Figure 1A; Materials and Methods).
Regarding claim 9, Shan discloses that the engineered Fc fragment further comprise YTE mutations known for IgG half-life extension (Figure 2A; Results section “Design and screening for monomeric IgG4 Fc”).
Regarding claims 17, 19-22, Shan discloses fusion proteins wherein a first antigen-binding domain is attached to the N-terminus of the FcRn binding fragment and a second antigen-binding domain is attached to the C-terminus of the FcRn binding fragment wherein the antigen binding domains are Fab or scFv (Figure 1B). Furthermore, the boxes labeled “Fc fusion protein” and “Monovalent Fc fusion protein” depict non-IgG protein domains attached to the FcRn binding fragment of the Fc fusion (Figure 1A).
Regarding claims 28-30, 34, 42, 43, Shan discloses nucleic acids encoding the Fc variants including clone 4C having recited mutations (Materials and Methods “Phage library”). Shan discloses vectors containing nucleic acid encoding the monomeric Fc variants. The Fc libraries and expression constructs were cloned into phage vectors and mammalian expression vectors for production and screening of the Fc variants (Materials and Methods “Phage library). Shan further discloses host cells comprising nucleic acids encoding the Fc variants. The Fc constructs of fusion proteins were expressed in mammalian host cells for production and purification (Material and Methods “Cloning, expression and purification of anti-cMet monomeric Fc fusion proteins”).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 24, 35, 41 and 44 are rejected under 35 U.S.C. 103 as being unpatentable over Shan et al. (PLOS One August 2016 e0160345) in view of Chamberlain et al. (WO 2009/058492 A2).
The teachings of Shan et al. have been discussed above (see 102).
Regarding claim 24, Shan teaches fusion of the monomeric FcRn-binding fragment to therapeutic proteins, including scFv, to generate therapeutic fusion proteins with extended serum half-life. However, Shan did not teach that the FcRn-binding fragment is conjugated to a non-protein agent.
Chamberlain teaches FcRn-binding Fc variants and Fc fusion constructs useful for extending serum half-life of therapeutic agents (paragraph 41). Chamberlain further teaches that the Fc domains and Fc variants may be linked, fused or conjugated to a broad range of non-protein agents, including radioisotopes (paragraphs 126-127). Therefore, it would have been obvious to one of ordinary skill in the art to conjugate the FcRn-binding fragment of Shan to other non-protein therapeutic compounds as taught by Chamberlain because both references teach FcRn-binding Fc domains as half-life extension platforms and recognize that coupling therapeutic agents to the FcRn-binding Fc molecules prolongs circulation time and improves pharmacokinetic performance.
Regarding claims 35, 41 and 44, Shan teaches a therapeutic Fc fusion protein comprising the FcRn-binding fragment (as described above) and Chamberlain teaches pharmaceutical compositions comprising FcRn-binding Fc variants and pharmaceutically acceptable carriers (paragraph 218). Therefore, it would have been obvious to formulate the Fc fusion protein of Shan into pharmaceutical composition as taught by Chamberlain because pharmaceutical formulation represents a conventional and necessary step for administration of therapeutic Fc-based molecules. Furthermore, it would have been obvious to administer said pharmaceutical composition to treat a subject given that Shan teaches therapeutic Fc fusion protein.
Therefore, the invention, as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention as evidenced by the references, especially in the absence of evidence to the contrary.
Allowable Subject Matter
Claims 14, 16, 27 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHARON X WEN whose telephone number is (571)270-3064. The examiner can normally be reached Mon-Fri 8-5.
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/SHARON X WEN/Primary Examiner, Art Unit 1641
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