CTNF 17/784,396 CTNF 87006 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Election/Restrictions The previous election/restriction requirement is WITHDRAWN. All claims are examined. Claim Rejections - 35 USC § 112 07-30-02 AIA The following is a quotation of 35 U.S.C. 112(b): (b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention. 07-34-01 Claims 1-13 are rejected 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. Claim 1 recites “low molecular weight” which is indefinite because “low” is a relative term of degree of which there is no requisite standard from which to determine what would be considered “low”. Claim Rejections - 35 USC § 103 07-06 AIA 15-10-15 In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status. 07-20-aia AIA 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. 07-23-aia AIA 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. 07-21-aia AIA Claim s 1-13 are rejected under 35 U.S.C. 103 as being unpatentable over Katz et al. (WO2017/044397) and further in view of Fraunhoffer et al. (US Pub. No. 2013/0156760) . Claim 1: Katz et al. teach a method of stabilizing a protein the method comprising providing an aqueous solution comprising a protein [0028, 0033] and the surfactant of formula I [0026]. They do not teach the separating steps. Fraunhoffer et al. teach an aqueous formulation comprising water and a protein (abstract) and excipients (abstract) wherein excipients are formulations that improve protein stability [0004]. Excipients include surfactants [0025]. They teach using diafiltration/ultrafiltration to selectively separate the solutions based on the molecular size of the components [0151]. Protein is retained in the retentate [0161]. When/if Formula I has a smaller size than the protein, it will pass through the membrane [0151]. The surfactant is reduced in the final solution [0162] by membrane separation. The excipient passes through the membrane [0260]. Katz et al. and Fraunhoffer et al. do not teach the outcome of using the Formula I in the protein solution. However, assuming the same protein, the compound will function in the same way that is to reduce aggregation as "Products of identical chemical composition can not have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). One of ordinary skill in the art at the time of the invention would have found it obvious to use Faunhoffer et al.’s diafiltration and/or ultrafiltration method to separate Katz et al.’s protein from the aqueous and surfactant solution in order to either exchange the buffer as is needed for further studying or use or to isolate the protein for clinical use. One of ordinary skill in the art at the time of the invention would have also found it obvious to modify Fraunhoffer et al. by Katz et al. to and try Katz et al.’s protein stabilizing compound because Fraunhoffer et al. discusses the use of surfactants for stabilizing proteins and “The selection of a known material, which is based upon its suitability for the intended use, is within the ambit of one of ordinary skill in the art. See In re Leshin, 125 USPQ 416 (CCPA 1960) (see MPEP § 2144.07).” Claim 2: the surfactant is reduced by at least 95% with respect to the protein in the initial solution [0162]. Claim 3: Katz et al. teach that the concentration of the surfactant in the aqueous solution is 1 mg/mL [0048]. Claim 4: Katz et al. teach that the concentration of the surfactant in the aqueous solution is 1 mg/mL [0048]. Fraunhoffer et al. teach that the membrane cut-off is a result effective variable that is optimized depending on the size of the protein molecule being separated/concentrated [0151]. The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.). Claim 5: Katz et al. teach that the concentration of the surfactant in the aqueous solution is 1 mg/mL [0048]. The concentration of the surfactant, also known as an excipient in the art, in a protein/surfactant aqueous solution is a result effective variable that is routinely optimized based on the amount of protein in the solution, the buffer type, and the desired aggregation/non-aggregation or other solution dynamics that the excipient affects. The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.). Fraunhoffer et al. teach that the membrane cut-off is 30 kDa [0151]. Claim 6: Katz et al. teach that the concentration of the surfactant in the aqueous solution is 1 mg/mL [0048]. The concentration of the surfactant, also known as an excipient in the art, in a protein/surfactant aqueous solution is a result effective variable that is routinely optimized based on the amount of protein in the solution, the buffer type, and the desired aggregation/non-aggregation or other solution dynamics that the excipient affects. The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.). Fraunhoffer et al. teach that the membrane cut-off is 30 kDa [0151]. Fraunhoffer et al. teach that diafiltration is an optional step/method performed in addition to ultrafiltration [0083-0084]. It is not required and, therefore, Fraunhoffer et al.’s disclosure meets the claim. Claim 7: Katz et al. teach that the concentration of the surfactant in the aqueous solution is 1 mg/mL [0048]. The concentration of the surfactant, also known as an excipient in the art, in a protein/surfactant aqueous solution is a result effective variable that is routinely optimized based on the amount of protein in the solution, the buffer type, and the desired aggregation/non-aggregation or other solution dynamics that the excipient affects. The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.). Fraunhoffer et al. teach that the membrane cut-off is 30 kDa [0151]. They teach that diafiltration can be followed by ultrafiltration [0083-0084]. Claim 8: Katz et al. teach that the concentration of the surfactant in the aqueous solution is 1 mg/mL [0048]. The concentration of the surfactant, also known as an excipient in the art, in a protein/surfactant aqueous solution is a result effective variable that is routinely optimized based on the amount of protein in the solution, the buffer type, and the desired aggregation/non- aggregation or other solution dynamics that the excipient affects. The discovery of an optimum value of a known result effective variable, without producing any new or unexpected results, is within the ambit of a person of ordinary skill in the art. See In re Boesch, 205 USPQ 215 (CCPA 1980) (see MPEP § 2144.05, II.). Fraunhoffer et al. teach that the membrane cut-off is 30 kDa [0151]. Ultrafiltration is not required in a separation process depending on the needs of the system and the goal of the separation [0083-0084]. Therefore, ultrafiltration is not required before and/or after diafiltration; that is diafiltration can be performed on its own. Claims 9-13: Katz et al. teach the structure recited in claims 9-13 is taught in the depiction of Formula I as explained in the rejection of claim 1, and the iterations and definitions of the groups of Formula I as described in Katz et al. Claim 9 is taught in [0020]. Claim 10 is taught in at least [0023] Claim 11 is taught in at least Claim 7 of Katz et al. Claim 12 is taught in at least [0047]. Claim 13 is taught in at least [0023] and [0047]. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALLISON FITZSIMMONS whose telephone number is (571)270-1767. The examiner can normally be reached M-F 9:30 am - 2:00 pm. 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, Magali Slawski can be reached at (571)270-3960. 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. ALLISON FITZSIMMONS Primary Examiner Art Unit 1778 /ALLISON G FITZSIMMONS/Primary Examiner, Art Unit 1773 Application/Control Number: 17/784,396 Page 2 Art Unit: 1773 Application/Control Number: 17/784,396 Page 3 Art Unit: 1773 Application/Control Number: 17/784,396 Page 4 Art Unit: 1773 Application/Control Number: 17/784,396 Page 5 Art Unit: 1773 Application/Control Number: 17/784,396 Page 6 Art Unit: 1773 Application/Control Number: 17/784,396 Page 7 Art Unit: 1773 Application/Control Number: 17/784,396 Page 8 Art Unit: 1773