DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of species SEQ ID NO: 252 for a first Fc domain and SEQ ID NO: 161 for a second Fc domain in the reply filed on 8/4/2025 is acknowledged.
Claims 10-12, 14, are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 8/4/2025.
Claims 1-9, 13, 15-19, 22-29 are pending and will be examined on the merits.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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 1-9, 13, 15-19, 22-29 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.
The claims recite limitations within parentheses that are not defining the terms preceding them. Thus, the limitations in parentheses renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP 2173.05(d). Appropriate correction required.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-9, 13, 15-19, 22-29 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This a written description rejection.
The claims are broadly drawn to an engineered, human IgG1 immunoglobulin or fragment thereof comprising a variant Fc region which is capable of binding and activates human FcαRI, capable of binding to human FcRn, and capable of binding to human FcγRs. However, the instant specification does not provide guidance on the specific amino acids that correlates to these claimed function other than the defined sequences listed in Table 51 of full length heavy chains comprising the variant Fc regions as described in the examples as well as the light chain used to generate complete antibodies. The instant specification does not provide a structure-to-function correlation for the broad scope of Fc variants encompassed by the instant claims and therefore do not show possession of the broad range of possible Fc variants. It is noted for example in claims 13 and 15 they recite “an amino acid sequence comprised within SEQ ID NO:” which reads on small amino acid fragments and do not require the entire SEQ ID NOs listed for the limitations to be met.
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. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 111 USPQ2d 1780 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention. “Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species.” Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010).
The prior art shows that specific amino acid substitutions within the Fc region can have varied altered effector functions. For example, Su et al. (Antibodies, 2018, 7, 20) teach IgA Fc mutations at positions C253Y/H304R in the CH3 region of IgA2 could effect antigen binding. The instant specification teaches specific amino acid mutations with defined substitutions in the Fc IgA2 region, however the broad genus of possible Fc variants encompassed by the instant claims is not adequately described.
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.
Claim(s) 1-9, 13, 15-19, 22-29 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Georgiou et al. (WO2014/065945, cited on IDS filed 5/23/2023).
The claims are drawn to an engineered, human IgG1 immunoglobulin or fragment thereof comprising a modified Fc regions and which is capable of binding and activating human FcαRI, capable of binding to human FcRn, and capable of binding to human FcγRs. The claims are further drawn to wherein the modification in the first Fc domain is a substitution that corresponds to an amino acid in an Fc domain of IgA1, an Fc domain of wild-type IgA2, an Fc domain of parental IgA2, or an affinity matured variant Fc domain of IgA1 or IgA2.
Georgiou et al. discloses a chimeric Fc polypeptide retaining the binding to IgA receptor CD89 of an IgA and the binding to IgG receptors FcγRI, RIIa, and RIIb of an IgG, ie. CD64 and CD32. This is exemplified with a swap recombinant IgA Fc comprising the sequence PALEDLLLGSEANG, corresponding to SEQ ID NO: 14 of Georgiou et al., which is the IgA alpha1 loop of a human IgA, next to an IgG CH2 domain and an IgA CH3 domain. It has been shown that when this sequence is inserted into a human IgG Fc CH2 fused to a human IgA Fc CH3 as defined in claim 8 of Georgiou et al., ie. comprising the amino acid sequence of SEQ ID NO: 9 of Georgiou et al., the mutant generated called Mutant D in Example 1, is capable of binding both FcαRI and FcγR (see example 1). HER2 target antigen binding capacity is exemplified in the case of trastuzumab (see Claims 1-31; Examples 1-9). Georgiou et al. discloses an engineered trastuzumab having a chimeric Fc polypeptide retaining the binding to IgA receptor and to receptors FcγRI, RIIa, and RIIb. Georgiou et al. further disclose “chimeric antibodies could be further modified by the additional of an FcRn binding peptide (FIG. 18), a modification that may increase serum half life of the molecules.” Georgiou et al. teach polynucleotides encoding the polypeptides and methods of producing the polypeptides of the invention comprising the antibodies having modified Fc regions. Georgiou et al. further teaches methods of treatment comprising administering said engineered immunoglobulins. It is noted in instant claims 13 and 15 they recite “an amino acid sequence comprised within SEQ ID NO:” which reads on small amino acid fragments, or for example the amino acid sequence “PALEDLLLGSEANG” taught by Georgiou et al. and present in several SEQ ID NOs from Table 51 of the instant application, and therefore do not require the entire SEQ ID NOs listed in the claims to meet the limitation.
Conclusion
Claims 1-9, 13, 15-19, 22-29 are rejected.
No Claims are allowed.
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/Meera Natarajan/Primary Examiner, Art Unit 1643