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 .
DETAILED ACTION
Status of the Claims
1. Claims 1-47 are the original claims filed 9/29/2022. In the Preliminary Amendment of 5/12/2025, Claims 4, 6, 10, 12-14, 21, 23-27, and 43-47 are amended and Claims 7, 8, 11, 15-20, 22, and 28-42 are cancelled. In the Response of 12/22/2025, claims 1, 13-14, 21 and 45 are amended and claims 2-6, 9-10 and 26-27 are canceled.
Claims 1, 12-14, 21, 23-25, and 43-47 are pending.
The finality of the rejection is withdrawn. The Office Action contains new grounds for objection and rejection pursuant to the Notice of Appeal Decision from the Pre-Appeal Brief Review of 8/17/2026.
Priority
2. USAN 17907,683, filed 09/29/2022, is a National Stage entry of PCT/IB2021/ 052589, International Filing Date: 03/29/2021, 17/907,683 Claims Priority from Provisional Application 63/002,631, filed 03/31/2020.
Information Disclosure Statement
3. As of 8/17/2026, a total of two (2) IDS are filed: 9/29/2022; and 7/12/2024. The corresponding initialed and dated 1449 is considered and of record.
Withdrawal of Rejections
Claim Rejections - 35 USC § 103
4. The rejection of Claim(s) 1, 12-14, 21, 23-25, and 43-47 under 35 U.S.C. 103 as being unpatentable over UCB Biopharma (US 11059911; filed 2013/02/22; “UCB”) is withdrawn.
Applicants allege UCB provides no expectation of success for just any combination of mutations, where instead in Example 5, col. 47, line 48- col. 49, line 2, col. 49, line 2, (col. 48, lines 51-57 and Figures 19-20, it is not predictable that triple mutations perform superior to double mutations. Applicants allege many mutations may not outperform double or triple mutations, and double and triple mutations do not perform similarly. Accordingly, UCB substantiates the combination of mutations is unpredictable for improved functionalized human IgG constant regions.
A reanalysis of the specific mutations for Y219C + G220C + S228P in light of specific improved properties of the combination of mutations that demonstrate improved stability towards reduction and reduced half mab formation substantiate the non-obviousness.
New Grounds for Rejection
Claim Rejections - 35 USC § 112
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.
Written Description
5. Claims 1, 12-14, 21, 23-25, and 43-47 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.
Claims 1, 12-14, 21, 23-25, and 43-47 are drawn to a genus of IgG4 antibodies comprising two human heavy chains where each chain comprises a human IgG4 constant region and the combination of mutations for Y219C + G220C + S228P according to EU numbering.
Inasmuch as the mutations are directed to the hinge region of the sequence of SEQ ID NO: 4 (Table 2), none of the claims recite the normal hinge sequence (SEQ ID NO: 7 in Table 2 [0068]). Nor is a normal human IgG4 heavy chain sequence recited in the claims that is amenable to mutation of any kind much less associated with the instant claimed hinge mutations. The specification teaching an exemplary IgG4 sequence amenable to mutation at
[0021] In particular embodiments provided herein is an IgG4 antibody comprising two heavy chains, wherein each of the heavy chains comprises a human IgG4 constant region comprising at least one mutation. In some embodiments, the heavy chain comprises a human IgG4 constant region comprising the amino acid sequence of SEQ ID NO: 11. In other embodiments, the heavy chain comprises a human IgG4 constant region comprising the amino acid sequence of SEQ ID NO: 11 with one or more mutation. In other embodiments, the IgG4 heavy chain constant region comprises the amino acid sequence of SEQ ID NO: 11 with one, two, or three mutations.
The specification teaching in the working examples that “the same IgG sequence” was used for the mutation experiments at
[0057] Hinge mutations were all incorporated into the same IgG4 sequence using site directed mutagenesis as previously described (Peng et al., PloS One 7: e36412 (2012); Bezabeh et al., mAbs 9: 240-56 (2017)). Mutated IgG4 sequences were expressed via transient transfection in CHO cells and purified using protein A chromatography followed by size exclusion purification to reduce product aggregates to <2%.
Applicants have not provided a copy of the Peng et al., PloS One 7: e36412 (2012) or Bezabeh et al., mAbs 9: 240-56 (2017) references in the IDS on file. Accordingly, the Office cannot ascertain the exact sequence used by Applicants in the generation of the IgG4 antibody shown in the examples and comprising the mutations for Y219C + G220C + S228P according to EU numbering that produced the unexpected results.
Thus, and from amongst any human IgG4 heavy chain constant region from which to choose, the POSA is given no guidance what mutations are permissible in any IgG4 heavy chain with even a reasonable expectation of improved function. Notably, the “comprising” language of the claims does not exclude other mutations occurring within a hinge region much less anywhere within the generic human IgG4 Fc constant region.
Finally, and from the disclosure in the specification, the wild type IgG4 heavy chain is considered a critical essential feature of the claimed invention. See for example MPEP 2163 stating in part:
"The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art."
"The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its function. A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence."
MPEP 2163.05 stating in part:
"A claim that omits an element which applicant describes as an essential or critical feature of the invention originally disclosed does not comply with the written description requirement."
New Grounds for Objection
Specification
6. The incorporation of essential material in the specification by reference to an unpublished U.S. application, foreign application or patent, or to a publication is improper. Applicant is required to amend the disclosure to include the material incorporated by reference, if the material is relied upon to overcome any objection, rejection, or other requirement imposed by the Office. The amendment must be accompanied by a statement executed by the applicant, or a practitioner representing the applicant, stating that the material being inserted is the material previously incorporated by reference and that the amendment contains no new matter. 37 CFR 1.57(g).
The attempt to incorporate subject matter into this application by reference to Peng et al., PloS One 7: e36412 (2012) or Bezabeh et al., mAbs 9: 240-56 (2017) is ineffective because the sequence information for the IgG4 heavy chain is essential to the disclosure and the replication of the invention by the POSA. The sequence information for the wild type IgG4 heavy chain much less the constant region is not ascertainable.
Conclusion
7. No claims are allowed.
8. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
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LYNN ANNE BRISTOL
Primary Examiner
Art Unit 1643
/LYNN A BRISTOL/Primary Examiner, Art Unit 1643
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