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 .
Claim Status
Claims 2-5 and 7-9 were canceled.
Claims 1, 6 and 10-11 are pending.
Claims 10-11 stay withdrawn from further consideration.
Claims 1 and 6 are under consideration.
Withdrawn Rejections
Rejection of Claims 1-7 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn. Applicant deleted wherein-clause “wherein the mass/volume used is in g/L” in claim 1 to overcome this rejection.
MAINTAINED - 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 1 and 6 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jiang et al (WO2018/052818; 7/5/2022 IDS) in view of Cao et al (WO2018/027524; 3/7/2024 IDS) and Sek et al (US2008/0139792).
Regarding claim 1, Jiang teaches “The invention provides a composition comprising the anti-PD-1 antibody”. Jiang teaches “In certain embodiments, the anti-PD-1 antibody is formulated in a buffer comprising 10 mM citrate, 100 mM NaCl, 100 mM glycine, and 0.01% polysorbate 80, wherein the formulation is at pH=5.5.” 100 mM NaCl corresponds to 0.58% (weight/volume) (100 mM = 0.1 mole/L x 58.4 g/mole = 5.84 g/L = 0.584 g/100 mL = 0.584 %). Jiang teaches “In certain embodiments, a formulation comprising 5 mg/ml, 10 mg/ml, 15 mg/ml, 20 mg/ml, or 25 mg/ml of an anti-PD-1 antibody described herein shows less than about a 1.6%, 1.4%, 1.2%, 1.0%, 0.8%, 0.6%, 0.4%, 0.2%, or 0.1% increase in high molecular weight species (HMWS) after 1 week at 37°C”. Jiang teaches “Acceptable carriers, excipients, or stabilizers are nontoxic to recipients at the dosages and concentrations employed, and include buffers such as phosphate, citrate … sugars such as sucrose, mannitol … ”.
Regarding claims 1 and 6, Jiang teaches anti-PD-1 humanized antibody VH protein, SEQ ID 8 which is 100% identical to instant SEQ ID NO: 10 (SCV; result 1 of 10.rag). Jiang teaches anti-PD-1 humanized antibody VL protein, SEQ ID 6 which is 100% identical to instant SEQ ID NO: 9 (SCV; result 1 of 9.rag). As evidenced by instant specification, paragraph 9 at page 3, VH and VL sequences of SEQ ID NO: 7 and 8 is a portion of heavy and light chain sequences of SEQ ID NO: 10 and 9, respectively. Furthermore, VH and VL sequences of SEQ ID NO: 7 and 8 must be a portion of heavy and light chain sequences of SEQ ID NO: 10 and 9, respectively, due to claim dependency because claim 6 depends from claim 1.
The difference between Jiang and the instant invention is that Jiang does not teach the concentration of mannitol (3%) recited by instant claim 1 and specific concentration of components recited by instant claim 1.
Regarding claim 1, Cao teaches a pharmaceutical composition comprising anti-PD-1 antibody (claim 1). Cao teaches a pharmaceutical composition wherein the concentration of the anti-PD-1 antibody is about 10 mg/mL, the concentration of citrate is about 20 mM, the concentration of mannitol is about 140 mM, the concentration of sodium chloride is about 50 mM, the concentration of polysorbate-80 is about 0.02％ (claim 12). 140 mM mannitol corresponds to 2.55 % (weight/volume) (140 mM = 0.140 mole/L x 182.17g/mole = 25.5 g/L = 2.55 g/100ml). 50 mM NaCl corresponds to 0.29 % (w/v) because 100 mM NaCl corresponds to 0.58% as discussed above).
In addition, another reference Sek teaches “Mannitol has been generally used in protein formulations for maintaining stability and isotonicity of the formulation”. Therefore, Sek teaches rational to add mannitol as an excipient in formulation.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have added mannitol taught by Cao into formulation taught by Jiang because Jiang suggests mannitol as an excipient, because Cao teaches that anti-PD-1 is stable in pharmaceutical composition comprising mannitol, and because Sek teaches that mannitol has been well known in the art as a stabilizer and isotonicity agent in protein formulation. Furthermore, Jiang and Cao teach antibody formulations which commonly comprise citrate, polysorbate 80 and NaCl. Therefore, one of ordinary skill in the art would be motivated to optimize formulation using buffer condition taught by Jiang and Cao. When general condition of buffer formulation was taught by prior art, it is obvious to one of ordinary skill in the art to change the concentration of each component to find optimal conditions for the given antibody. Finding optimal buffer condition for the given antibody is within routine skill of the skilled artisan in the art. Therefore, the invention as a whole would have been obvious to one of ordinary skill in the art.
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success because prior art teaches that anti-PD-1 antibody is stable in the formulation comprising citrate, mannitol, polysorbate 80, and NaCl. Therefore, the invention as a whole would have been 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.
Response to Arguments
In the response filed on 1/26/2026, Applicant argued at page 6,
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Applicant's arguments have been fully considered but they are not persuasive. PD-1 antibody is also stable in the formulation taught by Jiang and Cao. Otherwise, the formulations of Jiang and Cao could not have been effectively used as a pharmaceutical composition. Therefore, Applicant’s argument that instant formulation has good stability does not prove non-obviousness.
Furthermore, as shown below, the formulations of Jiang and Cao are very similar to instant invention.
Jiang Cao Instant Invention
PD-1 antibody 10 mg/ml 10 mg/ml 10 mg/ml
Citrate buffer 10 mM 20 mM 20 mM
Sodium Chloride 0.58% 0.29% 0.3%
Mannitol 2.55% 3%
Polysorbate 80 0.01% 0.02% 0.02%
pH 5.5 5.5-6.5 5.5
Especially, the formulation of Cao is almost same as instant invention. As discussed above, when general condition of buffer formulation was taught by prior art, it is obvious to one of ordinary skill in the art to change the concentration of each component to find optimal conditions for the given antibody. Finding optimal buffer condition for the given antibody is within routine skill of the skilled artisan in the art. Because Jiang and Cao teach that PD-1 antibody is stable in the buffer condition of Jiang and Cao, one of ordinary skill in the art would be motivated to optimize buffer condition of Jiang and Cao to find the optimal buffer condition.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/CHEOM-GIL CHEONG/Examiner, Art Unit 1645
/DANIEL E KOLKER/Supervisory Patent Examiner, Art Unit 1645