Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/11/2025 has been entered.
Applicants claim amendments and arguments filed 12/11/2025 are acknowledged.
Accordingly, Claims 1-24 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 .
New Grounds of Rejection
(based on reconsideration)
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.
Claim(s) 1-24 are rejected under 35 U.S.C. 103 as being unpatentable over Hong et al. (WO/2018/104893) in view of Rosario et al. (WO/2017/218434) and Singh et al. (Pharmaceutical Research 39:851-965, 2022).
The Claims are drawn to a method of treating inflammatory bowel disease comprising administering to a subject in need thereof a specific protocol including an induction dose and a maintenance dose of a long acting α4β7 targeting molecule having a heavy chain consisting of SEQ ID NO: 1 and a light chain consisting of SEQ ID NO: 3.
Hong et al. teach heavy chain variants of vedolizumab (see table 7) with modified properties. Claimed is an α4β7 antibody or a fragment thereof wherein the FcRn binding portion of the human lgG2 constant domain CH2 comprises an amino acid sequence selected from SEQ ID NO; 12, SEQ ID NO: 13 and SEQ ID NO: 14, wherein the α4β7 antibody or fragment thereof has an increased FcRn binding affinity at pH 6 and/or increased half-life as compared to an IgG comprising the light chain sequence of SEQ ID No: 9 and the heavy chain sequence of SEQ ID No: 10 (claim 6) for use in therapy (claim 7). SEQ 14 of Hong et al. is almost identical to SEQ ID No 1 of the present application and SEQ ID No 9 of Hong et al. is identical to SEQ ID No 3 of the present application. The difference between the vedolizumab variant of Hong et al. and the vedolizumab variant as claimed in present application is one amino acid difference in the heavy chain, i.e. SEQ ID No 1 of the present application comprises an additional C-terminal lysine. Hong et al. disclose “upon production of the antigen binding protein, in particular depending on the cell line used and particular amino acid sequence of the antigen binding protein, post-translational modifications may occur” including “C-terminal lysine clipping” (see paragraph [00163]. Hong et al. further disclose “the modification typically does not result in a change in antigen binding, function, bioactivity, nor does it impact the PK/PD.” There is no apparent technical effect associated with said difference. The mode of administration of the therapeutic agent of the invention may be any suitable route which delivers the agent to the host. The antigen binding proteins, and pharmaceutical compositions of the invention are particularly useful for parenteral administration, i.e., subcutaneously (s.c), intrathecally, intraperitoneally, intramuscularly (i.m.) intravenously (i.v.), or intranasally. In one embodiment the antigen binding proteins and pharmaceutical compositions of the invention are administered via a subcutaneous autoinjector pen or a subcutaneous pre-filled syringe (para 206). Hong et al. does not teach the specific patient population suffering from inflammatory bowel disease, Crohn’s disease or ulcerative colitis and the exact dosages and timings instantly claimed. These deficiencies are made up for by Rosario et al.
Rosario et al. teach “Vedolizumab, a humanized monoclonal antibody that binds specifically to the α4β7 integrin, is indicated for the treatment of patients with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD).” Rosario et al. teach methods comprising intravenously administering vedolizumab at a dose of 600 mg to the non-responder wherein the next dose and subsequent doses of vedolizumab is 300 mg wherein the vedolizumab responder is a human patient suffering from inflammatory bowel disease wherein the inflammatory bowel disease is ulcerative colitis (see claims of Rosario). Rosario et al. further discloses doses administered at eight week intervals (see claim 54 of Rosario).
Singh et al. teach an in-depth investigation of the impact of C- terminal lysine clipping of mAbs on safety and efficacy for bevacizumab charge variants. Singh et al. disclose C-terminal lysine clipping is a common phenomenon observed in CHO- derived mAb products and contributes to about 20-30% of the total charge heterogeneity. Singh et al. discloses therapeutic mAbs (IgGs 1, 2, and 4) have a lysine residue at the C- terminus of the heavy chain which get cleaved by the action of the carboxypeptidases present in the mammalian cells, however a fraction of mAb molecules have either one or both of the lysine residues at the C-terminus end due to incomplete processing. Singh et al. test variant 1 (K1) having one C-terminal lysine and variant 2 (K2) having two lysine residues at the C-terminus end intact. Singh et al. found K1 variant exhibited improved FcRn binding affinity (4-fold), half-life (1.3-fold), and anti-tumor activity (1.3-fold) as compared to the K0 (main) product. However, the K2 variant, even though exhibited higher FcRn affinity (2-fold), displayed lower half-life (1.6-fold) and anti-tumor activity at medium and low doses. Singh et al. discloses K1 variant offer superior therapeutic efficacy and better pharmacokinetic profile as compared to the main product.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to treat inflammatory bowel disease using a variant of vedolizumab having a C terminal lysine, as taught by Hong et al. and Singh et al., administered with an induction dose and subsequence maintenance doses, as taught by Rosario et al. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success based on the teachings of Hong et al. Singh et al. and Rosairo et al. In regards to the specific dosage and interval amounts recited in the instant claims "[w]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955), and see M.P.E.P. § 2144.05 II.A. Moreover, it is well settled that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804,809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989). This because, as is made clear from the prior art, the determination of the dosage regimen of a known drug is well within the purview of one of ordinary skill in the art at the time the invention was made, and it would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal intervals of treatment because optimal intervals is an art-recognized result-effective variable which would have been routinely determined and optimized in the pharmaceutical art. Therefore, it would be conventional and within the skill of the art to identify the optimal dosages administered and optimal intervals to achieve target levels and therapeutically effective doses. Further, it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art. It is clear that both the prior art and claimed method perform the same protocol to achieve the same results. It would be conventional and within the skill of the art to determine the optimal treatment regimens and to use a vedolizumab variant having one C-terminal lysine for a more efficient therapeutic antibody having superior pharmacokinetics for treatment of inflammatory bowel disease.
Conclusion
Claims 1-24 are rejected.
No Claim is allowed.
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/Meera Natarajan/Primary Examiner, Art Unit 1643