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 135-139, 155-161, 163-167, 169, 172-174, and 176-185 are presented for examination.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 04/22/2026 has been 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) 135-139, 155-161 and 163-167, 169, 171-174 and 176-185 is/are rejected under 35 U.S.C. 103 as being unpatentable over Garidel et al. (US 20210070582) in view of MacDonald et al. (Bioinformatic Analysis of Chinese Hamster Ovary Host Cell Protein Lipase, 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, such as PLA2G15 and the concentration of such agent in the liquid formulation. MacDonald et al. teach Chinese hamster ovary (CHO) cells are the preferred platform for biotherapeutic protein production. Monoclonal antibodies (mAbs) alone are predicted to reach global sales of US
$125 billion in 20201 and are used to treat many oncological, immunological, and cardiovascular diseases. During the production of therapeutic proteins by CHO cells, host cell proteins
(HCPs) are also secreted by the cells. Certain HCPs, if not removed during subsequent purification processes, have been shown to cause immunogenic responses in patients 2 and others
can shorten the shelf life of the final drug product through a variety of mechanisms including polysorbate degradation. HCPs, therefore, need be reduced to minimal levels, typically 1-100 ppm, in final mAb formulations. While most HCPs are removed from the therapeutic product during downstream purification steps, certain “difficult-to-remove” HCPs can remain. Several types of lipases have been identified as problematic HCPs, especially regarding the stability of the mAb product. See column 1. MacDonald et al. teach lipases, which have displayed polysorbate degradation activity and have been identified in CHO cell-derived drug products. Group XV lysosomal phospholipase A2 (LPLA2 or PLA2G15) was found in the drug product of several mAb-producing cell lines at less than 1 ppm. Even at these low levels, LPLA2 was associated with the hydrolysis of PS20 and PS80. The rate of polysorbate hydrolysis was
shown to be both time and concentration dependent. See column 2. 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.
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 PLA2G15. Therefore, lowering the amount of PLA2G15 taught by MacDonald and Hall in biotherapeutics which are produced in genetically engineered host cells, is expected to lower the free fatty acids produced by degrading polysorbate 20 and 80. It would have been obvious to a person skilled in the art to combine
PLA2G15 with a monoclonal antibody, taught by Garidel, motivated by the teachings of MacDonald et al., which teaches PLA2G15 is an impurity of Chinese hamster ovary cells used for producing monoclonal antibodies. The prior art makes clear that compounds produced by Chinese hamster ovaries are expected to have PLA2G15 impurities, which indicates that the claimed compound and the composition of Garidel and SKYRIZI already have PLA2gG15 impurity in the absence of evidence to the contrary. The lowering of the amount of PLA2G15 taught by MacDonald 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 PLA2G15 concentration in the claimed composition in order to obtain a more stable composition motivated by the teachings of MacDonald et al. , which teach the presence of PLA2G15 as impurities of Chinese ovary cells at the concentration of less than 1ppm. The presence of PLA2G15 is the inherent property of Garidel and SKYRIZI, considering that PLA2 and PLA2G15 is considered to be an impurity related Chinese hamster ovary cells used for producing monoclonal antibodies. The increase in concentration of free fatty acids following storage at 5 degree C is the expected property of Garidel in view of MacDonald and Hall, which teach the use of Risankizumab as a monoclonal antibody obtained from Chinese hamster cells and MacDonald and Hall, teach that monoclonal antibody obtained from Chinese Hamster cells have the impurity of PLA2G15, which causes polysorbate degradation and produces fatty acids as a result.
Response to Arguments
Applicant’s arguments have been noted. Applicant in his response argues that “Earlier compositions of Skyrizi, such as those disclosed or discussed in Garidel and the Guidance, were manufactured to enable the earlier FDA approved presentations of Skyrizi for treatment of psoriasis or psoriatic arthritis, all of which involved 90 mg/ml or 150 mg/ml concentrations of Risankizumab delivered subcutaneously by pre-filled syringes or single-dose pre-filled pens. At these concentrations, the earlier compositions did not present any challenges with surfactant stability, particle formation, or otherwise, and complied with all FDA guidance regarding antibody compositions.
However, when developing both a Risankizumab product presentation in a pre-filled cartridge and a 60 mg/ml composition in a vial (following FDA approval of earlier commercial formulations of Skyrizi in pre-filled syringes and single-dose pre-filled pens comprising 90 mg/ml and 150 mg/ml Risankizumab compositions for subcutaneous delivery), Applicant unexpectedly discovered that those earlier commercial formulations of Skyrizi, when diluted to 60 mg/ml, stored in a vial, and placed on stability tests, developed unacceptable particle content over time”. It is the examiner’s position that applicant is using a process to detect impurities on an existing product. The components of the claimed invention already exist in the Skyrizi approved by FDA. The discovery of impurities in Skyrizi does not create a patentably distinct composition. Furthermore, MacDonald and Hall teach that PLA2G15 at the concentration of less than 1ppm causes the degradation of polysorbate and are considered the cause of producing impurities of monoclonal antibodies obtained from Chinese hamster ovaries. Such concentrations read on the claimed composition. Additionally, the claims are not drawn to any specific concentration and dilution of such concentration with water to 60mg/ml. it is not clear why applicant decided to dilute the composition approved by FDA to 60mg/ml. There is also no comparison between the Skyrizi approved by FDA or taught by Garidel et al. in terms of efficacy and storage stability and the claimed composition.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sue Liu can be reached at 571-272-5539. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ZOHREH A FAY/Primary Examiner, Art Unit 1617
Prosecution Insights