PROCESS FOR PREPARATION OF STABLE PROTEIN SOLUTION

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 . DETAILED ACTION 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 6/1/26 has been entered. Amendment Entry 2. Applicant’s response to the Final Action mailed 30 December 2025 is acknowledged (reply filed 6/1/26). In the amendment filed therein claims 1, 5, and 6 were modified. Claims 2, 3, 4, 20, and 21 were cancelled without prejudice or disclaimer. Currently claims 1 and 5-19 are pending and under consideration. 3. Rejections and/or objections of record not reiterated herein have been withdrawn. Priority 4. This application claims priority to foreign application number 202121043419 filed on 9/24/21 in India. Accordingly, the application has been given a priority date of September 24, 2021. Information Disclosure Statement 5. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609 A(1) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the Examiner on form PTO-892 or Applicant on PTO-1449 cited the references they have not been considered. 6. The information disclosure statements filed 6/1/26 has been considered as to the merits. NEW GROUNDS OF REJECTIONS Double Patenting 7. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321 (d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AlA. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/applying-online/eterminal-disclaimer. 8. Claims 1 and 5-19 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 5, 10-19, 22-30, 32, 33, and 35 of copending Application No. 18/657,920 (reference application) in view of Ngo et al. (US 5,328,834) and Herigstad et al. (US 2016/0115193 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to a process for preparing an improved stable protein solution that is incubated with a protease inhibitor. The instant claims (1 and 5-19) differ from the claims in the reference application in reciting the utility of the Hydrophobic Interaction Chromatography Column (HIC) in step (e) is a two-step linear gradient for elution. However, the claims encompass a two-step linear gradient because claim 1 steps d and e broadly read on any HIC matrix and the specification defines the process as a two-step linear gradient on page 34 line 15. Additionally, the prior art teaches that HIC can be conducted in a two-step linear gradient. In particular, Ngo discloses a method for the separation of immunoglobulins and fragments thereof (abstract); the method entails the use of proteases to digest IgG and the subsequent use of complexing agents against the proteases to facilitate their removal (c2/58-62). In a first step, an intact IgG preparation is treated with a soluble protease (e.g., papain or pepsin) (i.e., protein solution comprising antibody treated with protease enzyme solution to separate Fab and Fc region of the antibody to form a digested protein solution; c4/49-52); the resultant digested protein solution is then treated with a corresponding antibody to the protease (e.g., antipapain or antipepsin) (i.e., treating the digested protein solution with a protease inhibitor to form a treated protein solution; c4/52-55). The treated protein solution is then loaded onto a separation column and eluted to collect undigested immunoglobulins (i.e., loading the treated protein solution; eluting the treated protein solution; c6/47-64). Reading on claim 1. Ngo further discloses proteolytic cleavage occurs at 37°C (e., incubating the digested protein solution at about 25 °C to about 60 °C; c6/36-38). While, Herigstad et al. disclose methods for purifying antibody products from a sample matrix employing hydrophobic interaction chromatography media (abstract). A sample mixture comprising the protein of interest, e.g., an antibody, is contacted with a hydrophobic interaction chromatography media in an aqueous salt solution under loading conditions that allow for the sample mixture to bind to the media; then under a similar aqueous salt composition, the bound sample is gradually eluted off of the media and collected in fractions of hydrophobic interaction chromatography; p0005; p0090; p0099, p0102). Thus, prior to the effective filing date of the claimed invention, one of ordinary skill in the art would have found it obvious to utilize hydrophobic interaction chromatography in a twostep linear gradient as suggested by Ngo et al. in view of Herigstad et al. for the separation of target proteins. The claim would have been obvious because the HIC was a particular known technique that was recognized as part of the capabilities of one of ordinary skill in the art (MPEP §2 143.01 D). Absent evidence to the contrary, it would have been prima facie obvious at the time of the filing date to employ a two-step HIC procedure to purify protein solutions as claimed to improved purity as taught by Ngo et al. and Herigstad et al. Therefore one of ordinary skill in the art would have been motivated to optimize protein purification techniques to achieve maximal compound benefits. Regarding the limitations “to separate Fab and Fc region of the antibody to form a digested protein solution”, “wherein the treated protein solution is free of sugar or polyol”, and has improved stability in comparison to a digested protein solution prepared without the addition of protease inhibitor’, such limitations are considered intended results from the practice of the claimed inventive process. Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed. A “whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” /d. (quoting Minton v. Nat 1 Assn of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620(Fed. Cir. 2003); MPEP § 2111.04). Where a reference discloses the terms of the recited method steps, and such steps necessarily result in the desired and recited effect, the fact that the reference does not describe the recited effect in haec verba is of no significance because the reference meets the claim under the doctrine of inherency. Regarding the limitation “wherein the protein sample is stable for at least about seven days at 2 °C to 8 °C’, such a limitation is directed toward properties of the claimed “protein sample”, namely, it’s stability under refrigeration storage. A number of factors are known to affect protein stability in refrigeration storage, including storage buffer composition. Applicant has further not specified the protein sample identity or even the class of proteins contained in the “protein sample”; certain proteins certainly have more stability in cold temperatures compared with other proteins. In any case, because Applicant has only generally referenced “protein” and because the prior art teaches protein purification, all claimed properties—including stability at 2°C to 8°C—are inherent. The claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the clam patentable Un re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977)). Furthermore, it is noted that the preamble “for the preparation of stable protein solution” is directed toward an intended use of the claimed process. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305,51 USPQ2d 1161, 1165 (Fed. Cir. 1999) (MPEP 2111.02 II). Regarding Claim 1, see claim 1 of the reference application. Regarding Claim 5, see claim 5 of the reference application. Regarding Claim 6, see claim 3 of the reference application. Regarding Claim 7, see claim 28 of the reference application. Regarding Claims 8 and 9, see claim 32 of the reference application. Regarding Claim 10, see claim 10 of the reference application. Regarding Claim 11, see claim 11 of the reference application. Regarding Claim 12, see claim 12 of the reference application. Regarding Claim 13, see claim 13 of the reference application. Regarding Claim 14, see claim 14 of the reference application. Regarding Claim 15, see claims 22 and 23 of the reference application. Regarding Claim 16, see claim 16 of the reference application. Regarding Claim 17, see claims 16 and 17 of the reference application. Regarding Claims 18 and 19, see claim 15 of the reference application. 9. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Response to Arguments In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case, Applicant’s arguments against Ngo and Herigstad for limitations that are found in application number 18/657,920 is not convincing. Ngo and Herigstad were merely relied on for teaching the two step linear HIC gradient. "Intended result" The Office alleges that "the preamble 'for the preparation of stable protein solution' is directed toward an intended use of the claimed process." Applicant states that the claims have been amended to recite that the stability is a property of the treated protein solution obtained from defined process steps, particularly the treatment with a protease inhibitor followed by HIC purification. Accordingly, the stability limitation defines a structural and compositional characteristic of the resulting product and is not merely an intended result. This argument was carefully considered but was not found persuasive because the limitations are recited in the claims of application #18/657,920. “Inherency” Applicant contends that neither Ngo nor Herigstad discloses omalizumab or the specific process conditions recited herein. Applicant submits that protein stability is highly dependent on protein identity, processing conditions, and purification methodology. This argument was carefully considered but was not found persuasive because the limitations are recited in the claims of Application #18/657,920. Further, Applicant argues that neither Ngo nor Herigstad provides any motivation or reasonable expectation of success for combining their teachings to achieve the claimed results. Because Ngo does not teach post- digestion stabilization, and Herigstad does not involve protease digestion or inhibitor use. Even if combined, the references would not lead to the claimed process or its technical benefits of stability for at least 7 days at 2-8 °C. This argument was carefully considered but was not found persuasive for the following reasons: In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, two-step linear HIC samples processing was taught by application number 18/657,920, Ngo, and Herigstad. It would have been obvious to optimize the HIC process in order to improve sample output and data analysis. In response to applicant's argument that the prior art references to Ngo and Herigstad are not concerned with stability, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). 10. For reasons aforementioned, no claims are allowed. 12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LISA COOK whose telephone number is 571-272-0816. The examiner works a flexible Part-Time schedule but can normally be reached on Monday, Thursday, and Friday from 9am to 5pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MISOOK YU can be reached at telephone number 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). 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) Form at https://www.uspto.gov/patents/uspto-automated- interview-request-air-form. Lisa V. Cook Patent Examiner Art Unit 1641 Remsen - Hoteling 571-272-0816 9/28/26 /LISA V COOK/Primary Examiner, Art Unit 1641