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 .
Claims 135-144, 155-161 and 163-175 are presented for examination.
The amendments and remarks filed on 12/03/2025 have been received and entered.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 135-144, 155-161 and 163-175 is/are rejected under 35 U.S.C. 103 as being unpatentable over Garidel et al. (US 20210070582) in view of Fischer et al. (Specific Immune Response to Phospholipase B-Like 2 Protein, a Host Cell Impurity in Lebrikizumab Clinical Material) and further in view of Hall et al. (Polysorbates 20 and 80 Degradation by Group XV Lysosomal Phospholipase A2 Isomer X1 in Monoclonal Antibody Formulations) and as evidenced by SKYRIZI product information.
Garidel teaches formulations comprising anti-IL-23p19 antibodies, such as risankizumab, which bind the p19 subunit of human IL-23. More specifically, pharmaceutical formulations comprising a high concentration of the anti-IL-23p19 antibody risankizumab, as well as related products and uses for the treatment of various diseases and disorders, are disclosed. Disclosed herein are stable liquid pharmaceutical formulations, comprising 150 mg/ml of the antibody risankizumab. See Para [0003]. Garidel teaches that Risankizumab is effective in the treatment of autoimmune and inflammatory diseases, in particular psoriasis. Clinical studies revealed excellent safety and efficacy of risankizumab in the treatment of plaque psoriasis. The recommended dose approved for treatment of psoriasis is 150 mg which is administered subcutaneously as two 75 mg injections, on week 0, 4 and thereafter every 12 weeks. See Para [0006]. The subcutaneous administration is taught in Para [0007]. The liquid formulation is taught in Para [0010]. The use of a buffer is taught in Paras [0012], [0061] and [0062]. The use of a tonicity agent is taught in Paras [0013] and [0032]. The use of a surfactant being polysorbate 20 and polysorbate 80 is taught in Paras [0046 and [0047]. Garidel teaches that In one embodiment, the antibody has been recombinantly produced in a hamster cell. In one embodiment, the antibody has been recombinantly produced in a CHO cell. See Para [0030]. Garidel does not teach the presence of phospholipase A2 and the concentration of such agent in the liquid formulation.
Fischer et al. teach biotherapeutics are produced in genetically engineered host cells, and although they
are manufactured under meticulously controlled processes to produce a therapeutic with a high degree
of purity, low residual amount of host cell proteins (HCPs) may potentially be associated with the
therapeutic products even after multiple purification steps. See column 1, introduction. Fischer teaches
that a Chinese hamster ovary (CHO) cell-derived process related impurity was detected in the material
originally intended for use in the phase III pivotal clinical studies of lebrikizumab. This impurity was
identified as CHO phospholipase B-like 2 (PLBL2) protein and was found in the drug product at 34-328
ng/mg concentration. See page 2. Fischer teaches of Chinese hamster ovary-derived, purified monoclonal antibodies. It was determined that polysorbate had been enzymatically degraded; therefore, studies were performed to identify and characterize the protein(s) responsible. Polysorbate degrading activity was enriched from Chinese hamster ovary media leading to the identification of group XV lysosomal phospholipase A2 isomer X1 (LPLA2) by shotgun proteomics. See the abstract. Hall et al. teach that interestingly, release of capric acid was preferred with approximately 55% hydrolysis whereas lauric acid was approximately 48% processed after 2 h of incubation. Most other fatty acid esters, including palmitic, stearic, oleic, gadoleic, and gadolenic acid were processed similarly between 35% and 45%. Such teaching shows free fatty acids are degradation byproduct of polysorbate by PLA2. Therefore, lowering the amount of PLA2 taught by Fischer in biotherapeutics which are produced in genetically engineered host cells, is expected to lower the free fatty acids produced by PLA2 by degrading polysorbate 20 and 80. It would have been obvious to a person skilled in the art to combine PLA2 with a monoclonal antibody, taught by Garidel, motivated by the teachings of Fischer, which teaches PLA2 is an impurity related to Chinese hamster ovary cells used for producing monoclonal antibodies. T he prior art makes clear that compounds produced by Chinese hamster ovaries are expected to have phospholipase A2 impurities, which indicates that the claimed compound and the composition of Garidel and SKYRIZI already have phospholipase A2 impurity in the absence of evidence to the contrary. The lowering of the amount of PLA2 taught by Fischer is considered to be as a contributory factor to safety and stability of the interleukin inhibitors. The use of water in SKYRIZI product (Risankizumab) for subcutaneous injection is taught by submitted product information.
It would have been obvious to a person skilled in the art to lower the PLA2 concentration in the claimed
composition in order to obtain a more stable composition motivated by the teachings of Fischer et al.
The presence of PLA2 is the inherent property of Garidel and SKYRIZI, considering that PLA2 is considered to be an impurity related Chinese hamster ovary cells used for producing monoclonal antibodies.
Applicant has presented no evidence to the unexpected or unobvious nature of the claimed invention,
and as such, claims 135-144, 155-161 and 163-175 are properly rejected under 35 U.S.C. 103 (a).
Response to Arguments
Applicant’s arguments have been noted. Applicant mentions each reference individually and argues that such reference does not teach the use of Risankizumab in combination with phospholipase A2 at the claimed concentrations. It is the examiner’s position that claims 165-167 do not have a lower limit for PLA2 concentration, considering that the phrase “less than about 250 pg “indicates the amount of PLA2 can be zero. Such claims read on the composition taught by Garidel and SKYRIZI article. Furthermore, Fischer makes clear that by changing the manufacturing process and lowering the amount of phospholipase in compounds being monoclonal antibody similar to the claimed compound there has been no safety signals attributed to the presence of PLB2 in lebrikizumab. It would have been obvious to a person skilled in the art to lower the PLA2 concentration in the claimed composition in order to obtain a more stable composition motivated by the teachings of Fischer et al.
The presence of PLA2 in the composition of Garidel and SKYRIZI is the inherent property of such compositions, considering that PLA2 is considered to be an impurity related Chinese hamster ovary cells used for producing monoclonal antibodies. There is no evidence of record to show the advantages of the claimed composition over the composition taught by Garidel and SKYRIZI, considering that Garidel and SKYRIZi’s composition is expected to have PLA2 as impurities, since they were obtained from Chinese hamster ovaries. The prior art makes clear that compounds produced by Chinese hamster ovaries are expected to have phospholipase A2 impurities.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ZOHREH A FAY whose telephone number is (703)756-1800. The examiner can normally be reached Monday-Friday 9:30AM-6:00.
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/ZOHREH A FAY/Primary Examiner, Art Unit 1617