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 1-9, 11, 13-14, 16-21, 24, and 26 are pending and under consideration.
Specification
3. The disclosure is objected to because of the following informalities: The specification filed 01/18/2024 is objected on page 16, paragraph 0073 for recitation of an amino acid sequence in the absence of a sequence identifier. See 37 CFR 1.821(c). 37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825.
4. Alternatively, since Table 1 underlines the CPPC sequence, applicants could amend the specification by reference to these residues according to their numeric position, as in AA 2-10 of SEQ ID NO:1.
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) 1-9, 11, 13-14, 16-21, 24, and 26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Cottingham et al. (WO 2016087941, published June 2016) in view of Gutka, H. “Rational Selection of Sugars for Biotherapeutic Stabilization”, BioProcess Intl, 16(10), October 2018 and further evidenced by CN106390115 (02-15-2017, English translation attached) and Joerg et al (PG-PUB 2017/0368174, December 2017).
The claims are drawn to an aqueous histidine salt buffer formulation comprising a fusion protein of SEQ ID NO:1 wherein the fusion protein comprises two monomers (e.g. a dimer). SEQ ID NO:1 is well known as the “gp130-Fc fusion” monomer. Also referred to as TJ301, FE999301 and Olamkicept (See clinical trial protocol CTJ301UC201, attached). Dimer formulations of the gp130-fusion product were well known prior to applicant’s filing date. For example, Cottingham et al. (WO 2016087941, published June 2016) teach 100% identity to applicant’s SEQ ID NO:1 (see comparison below) and state that the present sequence is a gp130-Fc fusion monomer comprising the extracellular domain of gp130 (gene ID 3572) transcript variant 1 and Fc domain of human IgG1 used for preparing the polypeptide dimer for treating an inflammatory disease.
PNG
media_image1.png
764
674
media_image1.png
Greyscale
PNG
media_image2.png
754
646
media_image2.png
Greyscale
PNG
media_image3.png
500
622
media_image3.png
Greyscale
9. Regarding claims 11 and 13, and because the two structures are identical, the prior art structure would inherently comprise no more than six galactose-α-1,3-galactose moieties and wherein, on average, at least 52% of the glycans comprise one or more sialic acid residues.
Further, Cottingham exemplifies [0069, 0106] one particular histidine salt buffer formulation for the drug product as comprising 15mg/mL of peptide, 25 mM histidine, 200 mM sucrose and 0.1 mg/mL of polysorbate 20 at pH 7.6. As to claim 18-19, this formulation did not comprise any additional amino acid salts or additional sugars higher than 10mM other than the histidine or trehalose.
As to claim 24, Cottingham et al. teach (see claim 18 of Cottingham) wherein the inflammatory disorder or IL-6 mediated condition is rheumatoid arthritis, psoriasis, uveitis or atherosclerosis.
10. Cottingham does not describe other variations of their formulation such as using trehalose or polysorbate 80 as set forth in Claim 1. Cottingham also does not teach a dry formulation, which can be obtained by lyophilization (Claim 26).
11. Gutka provides an overview of sugars for biotherapeutic stabilization and states (page 46, column 1) that a literature review reveals that each sugar stabilizer (sucrose, trehalose, mannitol, sorbitol, glucose, and lactose) has been studied extensively for its stabilization effect with several different biotherapeutic modalities: antivenoms, protein-based vaccines, peptides, fusion proteins, and antibodies (all isoforms). All such modalities have unique biochemical and biophysical properties. Although some or all of those sugars work as excellent stabilizers for given modalities, it is widely acknowledged that because each biotherapeutic presents unique formulation challenges, formulation development must be case by case and varies significantly depending upon protein concentration and final dosage form- e.g., “lyophilized solids or liquid compositions”. However, because biotherapeutic material availability often is limited during early stage of product development, the general industrial approach is to try a stabilizer that works best for most molecules. For example, (page 44, 3rd column) a careful survey of recently approved antibody-based products suggests that a histidine buffer (pH 5.5–6.5), a disaccharide stabilizer (trehalose or sucrose), and a surfactant (polysorbate 20 or 80) can provide a good platform formulation composition. Once such a prototype platform formulation composition is identified, sample-sparing HT (high throughput) approaches can be used to identify the most stabilizing composition and optimize the concentration of each stabilizing excipient.
12. Along these lines, CN106390115 (02-15-2017) discloses several optional formulations of a humanized monoclonal antibody convenient for large-scale production, storage and transportation. The isotonic regulator of the present invention is selected from one of sodium chloride, sucrose, mannitol, sorbitol, and trehalose or a combination thereof, and is more optimally 125mM NaCl, 250mM sucrose, 250mM mannitol, 250mM sorbitol, 250mM trehalose. The surfactant of the present invention is selected from 0.01%-0.2% polysorbate 20, 0.01-0.2% polysorbate 80 or a combination of both. In the anti-PD-1 monoclonal antibody preparation of the present invention, the surfactant is more preferably 0.01%-0.02% polysorbate 20 or 0.01%-0.02% polysorbate 80. The buffer pH range is 5.5-6.5.
13. Similarly, Joerg et al (PG-PUB 2017/0368174, December 2017) teach stable liquid compositions of IL-17 antibodies and antigen binding fragments thereof (secukinumab). For example, Joerg et al. teach [0012] stable liquid pharmaceutical compositions comprising about 25 mg/mL to about 150 mg/mL of an IL-17 antibody disclosed herein (e.g., secukinumab), about 10 mM to about 30 mM buffer (e.g., histidine) pH 5.8, about 200 mM to about 225 mM stabilizer (e.g., trehalose), about 0.02% surfactant (e.g., polysorbate 80), and about 2.5 mM to about 20 mM methionine.
14. One of ordinary skill in the art at the time of filing would consider it prima facie obvious to further optimize the pharmaceutical formulation of Cottingham et al. because the screening for stabilizers during the early stage of drug development is fairly liberal (Gutka, page 44) and would be considered routine in the industry. For example, it is widely acknowledged that because each biotherapeutic presents unique formulation challenges, formulation development must be case by case. The general industrial approach is to try a stabilizer that works best for most molecules. Further, it is well recognized that either liquid compositions or lyophilized drug products are a popular choice. It would have been nothing short of routine for a product stabilization team to experiment with different established sugars such as trehalose at different concentrations and to test different pH levels as the art has already taught that these salt buffers and sugar stabilizers are well known in the art. Moreover, as Gutka states, a careful survey of recently approved antibody-based products suggests that a histidine buffer (pH 5.5–6.5), a disaccharide stabilizer (trehalose or sucrose), and a surfactant (polysorbate 20 or 80) can provide a good platform formulation composition.
15. MPEP § 2144.05(II)(A) states, "[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). Additionally, KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007), discloses that the simple substitution of one known element for another to obtain predictable results is obvious unless its application is beyond that person's skill.
16. KSR International Co. v. Teleflex Inc., 127 S. Ct. 1727, 1741 (2007) also discloses that "the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results". In the instant case, all of the claimed excipients (trehalose, histidine, and polysorbate 80) were well-known in the art as stabilization agents and were used at similar concentrations using similar protein drugs prior to applicant’s filing date according to the patented literature of Joerg et al and CN106390115. Thus, applicant’s claiming of buffer formulations comprising specific concentrations of a histidine salts, trehalose, and polysorbate 80 at particular pHs would have been obvious as well as dry formulations thereof.
17. No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY B NICKOL, Ph.D. whose telephone number is (571)272-0835. The examiner can normally be reached M-F 9AM-5:30PM.
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, Julie Wu can be reached at 571-272-5205. 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.
/GARY B NICKOL/Primary Examiner, Art Unit 1643