DETAILED ACTION
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 .
Status of the Application
1. Claims 1-32 are pending and subject to examination on the merits. Claims 1-20 are withdrawn from consideration as being drawn to non-elected subject matter. Claims 21-32 are currently under examination.
Priority
2. Acknowledgment is made for the Applicant’s claim for domestic priority based on the US provisional application PRO 63/337,532 filed 02 May 2022.
Withdrawal of Species Election
3. The species election dated 17 February 2026 is withdrawn, since the Applicant argued that the species were ambiguous due to missing claim numbers (See Examiner Interview Summary dated 07 April 2026).
Election/Restrictions
4. Restriction to one of the following inventions is required under 35 U.S.C. 121:
I. Claims 1-15, drawn to a method for producing a pharmaceutical composition with reduced lipase activity, comprising: (a) subjecting a sample including a protein of interest and a lipase to stress conditions to form a sample with an inactivated lipase, and (b) formulating said sample with inactivated lipase to produce a pharmaceutical composition with reduced lipase activity, classified in C07K 1/36.
II. Claims 16-20, drawn to a method for producing a pharmaceutical composition with reduced lipase activity, comprising: (a) subjecting a drug substance including a protein of interest and a lipase to heat stress to form a with an inactivated lipase, and (b) subjecting said drug substance with inactivated lipase to cation exchange chromatography to form a HMW-depleted drug substance, and (c) formulating said HMW-depleted drug substance to produce a pharmaceutical composition with reduced lipase activity, classified in C12Y 301/01034.
III. Claims 21-32, drawn to a method for producing dupilumab pharmaceutical composition with reduced lipase activity, comprising: (a) subjecting a sample including dupilumab and a lipase to stress conditions to form a sample with inactivated lipase, and (b) formulating said sample with inactivated lipase to produce a dupilumab pharmaceutical composition with reduced lipase activity, classified in A61K 2239/13.
Inventions I and II are unrelated. Inventions are unrelated if it can be shown that they are not disclosed as capable of use together and they have different designs, modes of operation, and effects (MPEP § 802.01 and § 806.06). In the instant case, the different inventions are distinct methods for producing pharmaceutical compositions, where specifically invention II requires heat stress and invention I does not require this stress.
Inventions I and III are unrelated. Inventions are unrelated if it can be shown that they are not disclosed as capable of use together and they have different designs, modes of operation, and effects (MPEP § 802.01 and § 806.06). In the instant case, the different inventions are distinct methods for producing pharmaceutical compositions, where specifically invention III requires the utilization of dupilumab and invention I can utilize any protein of interest.
Inventions II and III are unrelated. Inventions are unrelated if it can be shown that they are not disclosed as capable of use together and they have different designs, modes of operation, and effects (MPEP § 802.01 and § 806.06). In the instant case, the different inventions are distinct methods for producing pharmaceutical compositions, where specifically invention III requires the utilization of dupilumab and invention II can utilize any protein of interest.
5. During a telephone conversation with Jonathan Caplan on 07 April 2026 a provisional election was made without traverse to prosecute the invention of invention III, claims 21-32. Affirmation of this election must be made by applicant in replying to this Office action. Claims 1-20 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Specification
6. The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (p. 33-34, paragraph 0133). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
7. The use of the terms MabSelect PrismA™, MabSelect SuRe™ LX, MabSelect™, MabSelect SuRe™ pcc, MabSelect Xtra™, and MabCapture™ (p. 25; paragraph 106); Macro-Prep CM™, Dowex MAC-3™, CM-Sepharose™ Fast Flow, SP-Sepharose™ Fast Flow or SP-Sepharose™ High Performance (p. 26, paragraph 109); Capto™ Adhere, Capto™ MMC, MEP HyperCell™ (p. 27, paragraph 110), Poros™ 50PI and Poros™ 5OHQ, Poros™ 5OXQ; Capto™ Q Impres, Capto™ DEAE, Capto™ Adhere, Toyopearl™ QAE-550, Toyopearl™ DEAE-650, and Toyopearl™ GigaCap Q-650, Sartobind™ Q nano, CUNO BioCap™, UNOsphere™ Q (p. 29, paragraph 0119) which are trade names or a marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or , where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
8. Claim 26 objected to because of the following informalities: “at from” in line two should be “from” to improve grammar. Appropriate correction is required.
9. Claim 27 objected to because of the following informalities: “for from” in line two should be “from” to improve grammar. Appropriate correction is required.
10. Claim 28 objected to because of the following informalities: “at from” in line two should be “from” to improve grammar. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
11. 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.
12. Claims 21-32 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.
18. Claim 21 recites the limitation "said sample" in part (b). It is unclear which “sample” of claim 21 part (a) is being referenced, since claim 21 part (a) recites two instances of “a sample.” There is insufficient antecedent basis for this limitation in the claim. Claims 22-32 are included in the instant rejection because they do not mitigate the issue.
19. Claim 21 is indefinite for reciting “reduced lipase activity” without reciting a comparison, i.e. is lipase activity reduced relative to the sample before stress or to some unperturbed cellular lipase? Claims 22-32 are included in the instant rejection because they do not mitigate the issue.
20. Claim 22 recites the limitation "said sample" in line 2. It is unclear which “sample” of claim 21 is being referenced, since claim 21 recites three instances of “a sample.” There is insufficient antecedent basis for this limitation in the claim. Claims 23-24 are included in the instant rejection because they do not mitigate the issue.
24. Claim 29 recites the limitation "said sample" in line 1. It is unclear which “sample” of claim 21 is being referenced, since claim 21 recites three instances of “a sample.” There is insufficient antecedent basis for this limitation in the claim. Claims 30-31 are included in the instant rejection because they do not mitigate the issue.
25. Claim 32 recites the limitation "said sample" in line 2. It is unclear which “sample” of claim 21 is being referenced, since claim 21 recites three instances of “a sample.” There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 103
26. 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.
27. 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.
28. Claims 21-22, 25, and 28 are rejected under 35 U.S.C. 103 as being unpatentable over Graf et al (Graf et al., 2021, Journal of Pharmaceutical Science—cited on the IDS dated 08 January 2026), Lim et al (Lim et al., 2018, Biotechnol. Prog.—cited herein), and FDA (“Quality Review BLA 761055 Dupixent (dupilumab)”, 2017, downloaded 15 April 2026 from < https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761055Orig1s000ChemR.pdf> as a PDF—cited herein) and CSB deepSTABp (cited herein).
Regarding claims 21-22, 25, and 28, drawn to a method of producing a dupilumab pharmaceutical composition with reduced lipase activity, comprising: (a) subjecting a sample including dupilumab and a lipase to stress conditions to form a sample with inactivated lipase, and (b) formulating said sample with inactivated lipase to produce a dupilumab pharmaceutical composition with reduced lipase activity, wherein said formulating step comprises adding a fatty acid ester to said sample, wherein said fatty acid ester is polysorbate 20 (claim 22), and further, the stress condition is heat (claim 25), specifically 30-60oC (claim 28), Graf et al. teaches the identification and characterization of polysorbate-degrading enzymes in a monoclonal antibody formulation (title, abstract), since the degradation of polysorbate by hydrolytically active host cell proteins in drug products may impair the protein-stabilizing properties of polysorbate. Specifically, Graf et al. teaches that CHO cell putative phospholipase B-like 2 (PLBL2) and lysosomal phospholipase A2 (LPLA2) have both been implicated in polysorbate degradation in drug products (p. 3558, column 2, paragraph 1). Graf et al. continues to teach that polysorbate 20 and polysorbate 80 represent the most common class of surfactants in biopharmaceutical formulations and have set the benchmark in terms of protein stabilizing properties, biocompatibility and safety (p. 3558, Introduction, paragraph 1). Additionally, polysorbate degradation was shown to be concomitant with the accumulation of free fatty acids, generally attributed to enzyme-catalyzed hydrolysis from trace amounts of host cell proteins (p.3558, Introduction, column 2, paragraph 2).
Graf et al. does not teach the utilization of a specific stress condition, such as heat shock, to a dupilumab and lipase containing pharmaceutical composition to inactivate or decrease the activity of the lipase. Lim et al. teaches the identification of an endoproteolytic activity endogenous to the Chinese hamster ovary cells, identified as cathepsin D, after the purification of a recombinant therapeutic protein from Chinese hamster ovary cells, leading to the degradation of hydrophobic amino acid residues of the recombinant therapeutic protein after storage as a solution (abstract). Further, the identification of cathepsin D, and its subsequent inactivation by heat inactivation, essentially inactivated the protease, resulting in the production of a stable drug product that had not been possible using column chromatography alone (abstract). Specifically, Lim et al. determined that the protease began to thermally unfold above 45oC, where the Tm was 53oC; therefore, Lim et al. targeted a temperature of 53-55oC for heat inactivation of the protease without affecting the structure of the fusion protein, which had a Tm of 65oC (p. 128, column 1, paragraph 1). Lim et al. achieved thermal heat inactivation of the protease with agitation and reported no detrimental impact on the quality of the fusion protein (p. 128, column 1, paragraph 2).
It is notable that the PLBL2 lipase from Chinese hamster ovary cells (the protein taught above by Graf et al. as implicated in polysorbate degradation) has a calculated Tm of 53oC, which is the same Tm for the protease taught by Lin et al.l (See CSB deepSTABp).
Graf et al. and Lin et al. do not teach dupilumab with a lipase. The FDA teaches that dupilumab is produced in CHO cells (p. 45, Introduction, paragraph 1). Additionally, the FDA teaches host cell proteins are found in the formulation of dupilumab (p. 11, CQA: Host Cell Proteins; third entry).
Therefore, it 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 combine the teachings of Graf et al., Lim et al., and FDA to utilize heat shock as a method to inactivate a lipase contaminant in the dupilumab formulation to inactivate the lipase without the subsequent addition of chemical inhibitors, since Graf et al. teaches that lipases are readily found in Chinese Hamster Ovary (CHO) cell derived monoclonal antibodies (p. 3559, paragraph 1) (and the FDA determined the presence of CHO cell derived host cell proteins in dupilumab formulations), and Lim et al. teaches that heat shock can be utilized to inactivate host cell proteins in protein formulations derived from CHO cells. One would be motivated to combine these teachings to arrive at the instant claims to increase shelf life of monoclonal antibodies, such as dupilumab, with polysorbate as taught by Graf et al. There would be reasonable expectation of success, yielding no surprising results when combining the teachings of Graf et al., Lim et al., and FDA, since Lim et al. teaches the determination of Tm and the subsequent utilization of heat shock to affect the unwanted protein in the formulation without perturbing the protein of interest.
29. Claims 23-24 and 32 are rejected under 35 U.S.C. 103 as being unpatentable over Graf et al (Graf et al., 2021, Journal of Pharmaceutical Science—cited on the IDS dated 08 January 2026), Lim et al (Lim et al., 2018, Biotechnol. Prog.—cited herein), and FDA (“Quality Review BLA 761055 Dupixent (dupilumab)”, 2017, downloaded 15 April 2026 from < https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761055Orig1s000ChemR.pdf> as a PDF—cited herein) as applied to claims 21-22, 25, and 28 above, and further in view of Grabarek et al (Grabarek et al., 2020, Journal of Pharmaceutical Sciences—cited herein).
The teachings of Graf et al., Lim et al., and FDA are discussed above and incorporated into the instant rejection. Graf et al., Lim et al., and FDA do not teach polysorbate 80, with oleic acid esters of at least 98%. Grabarek et al. teaches the utilization of polysorbate 80 with an oleic acid ester content of 98%, ChP-PS80, which the Chinese Pharmacopeia (ChP) set more stringent purity requirements for the fatty acid distribution in 2015 (p. 872, column 1, paragraph 2), where this polysorbate 80 with 98% of oleic acid retained its functionality even at 50% hydrolysis testing (p. 879, first column, 3rd paragraph). Additionally, Grabarek et al. teaches that the development of robust formulations consisting of excipients mitigating protein unfolding and aggregation is required to ensure the quality of protein drug products (p. 871, “Introduction,” paragraph 1).
Therefore, it 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 combine the teachings of Graf et al., Lim et al., and FDA in further view of Grabarek et al. to utilize polysorbate 80 with at least 98% oleic acid content as an excipient to ensure functionality of the polysorbate in a biopharmaceutical to insure functionality even after up to 50% hydrolysis of the polysorbate as taught by Grabarek et al. One would be motivated to combine these teachings to arrive at the instant claims to reduce protein aggregates, which deteriorate product quality and may compromise safety by causing unwanted immune responses as taught by Grabarek et al (p. 871, Introduction, 1st paragraph). There would be reasonable expectation of success, yielding no surprising results when combining the teachings of Graf et al., Lim et al., and FDA in further view of Grabarek et al. to utilize polysorbate 80 with 98% oleic acid content as an additive in a biopharmaceutical, since Grabarek et al. teaches the utilization of 98% oleic acid polysorbate 80 in biopharmaceuticals exposed to stress conditions.
30. Claims 26-27 are rejected under 35 U.S.C. 103 as being unpatentable over Graf et al (Graf et al., 2021, Journal of Pharmaceutical Science—cited on the IDS dated 08 January 2026), Lim et al (Lim et al., 2018, Biotechnol. Prog.—cited herein), and FDA (“Quality Review BLA 761055 Dupixent (dupilumab)”, 2017, downloaded 15 April 2026 from < https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761055Orig1s000ChemR.pdf> as a PDF—cited herein) as applied to claims 21-22, 25, and 28 above, and further in view of Chung et al (Chung et al., 2020, catalysts—cited herein).
The teachings of Graf et al., Lim et al., and FDA are discussed above and incorporated into the instant rejection. Additionally, Graf et al. teaches the release of free fatty acids, lauric acid and myristic acid, over time at a temperature of 30oC under shaking at 200rpm in two batch samples of antibody-1, where the release of free fatty acids is inhibited with the addition of the lipase inhibitor orlistat (p. 3560, Fig. 1; p. 3561, Results and Discussion: Identification of HCPs after enrichment).
However, Graf et al., Lim et al., and FDA do not teach the utilization of agitation from 50-500 rpm for 1-96 hours as a method to inactivate a lipase in a dupilumab containing pharmaceutical. Chung et al. teaches that shaking Lipase A produced on the surface of E. coli decreases the specific activity of the enzyme at speeds over 100 rpm, as a result of shear stress (abstract). Specifically, the 200 rpm shaking rate was utilized for 12 hours (p. 11, “Cultivation Conditions”).
Therefore, it 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 combine the teachings of Graf et al., Lim et al., and FDA in further view of Chung et al. to utilize agitation, specifically 200 rpm for 12 hours to inactivate a lipase without the subsequent addition of chemical inhibitors, since Graf et al. teaches that lipases are readily found in Chinese Hamster Ovary (CHO) cell derived monoclonal antibodies (and the FDA determined the presence of CHO cell derived host cell proteins in dupilumab formulations), and Chung et al. teaches that agitation can be utilized to inactivate lipases. One would be motivated to combine these teachings to arrive at the instant claims to increase shelf life of monoclonal antibodies, such as dupilumab, with polysorbate as taught by Graf et al. There would be reasonable expectation of success, yielding no surprising results when combining the teachings of Graf et al., Lim et al., and FDA in further view of Chung et al., since Chung et al. teaches shaking/agitation of lipase containing cultures at 200 rpm for 12 hours results in the inactivation of the lipase.
31. Claims 29-31 are rejected under 35 U.S.C. 103 as being unpatentable over Graf et al (Graf et al., 2021, Journal of Pharmaceutical Science—cited on the IDS dated 08 January 2026), Lim et al (Lim et al., 2018, Biotechnol. Prog.—cited herein), and FDA (“Quality Review BLA 761055 Dupixent (dupilumab)”, 2017, downloaded 15 April 2026 from < https://www.accessdata.fda.gov/drugsatfda_docs/nda/2017/761055Orig1s000ChemR.pdf> as a PDF—cited herein) as applied to claims 21-22, 25, and 28 above, and further in view of Gillmeister et al (Gillmeister et al., 2021, US 2021/0163991 A1—cited herein).
The teachings of Graf et al., Lim et al., and FDA are discussed above and incorporated into the instant rejection.
Graf et al., Lim et al., and FDA do not teach the utilization of cation exchange chromatography or size exclusion chromatography to remove high molecular weight species. Gillmeister et al. teaches improved methods for producing recombinant Adeno-Associated Virus particles/proteins by culturing cells in the presence of HDAC inhibitors and increased amounts of sodium salts (abstract). Specifically, the methods pertain to expressing an intact mAb, such as dupilumab (p. 20, column 2, line 16; paragraph 0259). Additionally, Gillmeister et al. teaches isolating the particles via downstream processing such as cation exchange chromatography and size exclusion chromatography (paragraph 0276).
Therefore, it 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 combine the teachings of Graf et al., Lim et al., and FDA in further view of Gillmeister et al. to utilize cation exchange chromatography and/or size exclusion chromatography to isolate a dupilumab containing particle from adeno-associated virus based vector expressing cells because adeno-associated virus based vectors are the most widely used gene therapy products in development as taught by Gillmeister et al (paragraph 0002). One would be motivated to combine these teachings to arrive at the instant claims to isolate a dupilumab containing biological, since adenovirus associated vectored biologics indicate great potential for delivery in gene therapy indications, as taught by Gillmeister et al (paragraph 0002). There would be reasonable expectation of success, yielding no surprising results when combining the teachings of Graf et al., Lim et al., and FDA in further view of Gillmeister et al. to utilize cation exchange chromatography and/or size exclusion chromatography to isolate a dupilumab containing particle, since Gillmeitster et al. teaches the isolation of dupilumab by the chromatography techniques.
Double Patenting
32. 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 AIA . 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/apply/applying-online/eterminal-disclaimer.
33. Claims 21-32 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 and 13-14 of copending Application No. 18/934,626 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘626 would necessarily anticipate the instant claims.
The instant claims in the broadest are drawn to a method for producing a dupilumab pharmaceutical composition with reduced lipase activity, comprising subjecting a sample including dupilumab and a lipase to stress conditions to form a sample with inactivated lipase; and formulating said sample with inactivated lipase to produce a dupilumab pharmaceutical composition with reduced lipase activity. Dependent claims 22-23 and 32, are drawn to the addition of polysorbate 80. Dependent claims 25-26 are drawn to the stress condition being agitation from 50-500 rpm for 1-96 hours. Dependent claim 28 is drawn to the stress condition being heat stress from 30-60oC. And dependent claims 29-31 are drawn to the utilization of cation exchange and/or size exclusion chromatography to deplete the sample of HMW species.
The ‘626 claims are drawn to a method for producing a pharmaceutical composition with reduced lipase activity, comprising subjecting a sample including a protein of interest, wherein said protein of interest is a monoclonal antibody (claim 2), wherein said protein of interest is dupilumab (claim 3), to a stress condition to form a sample with inactivated lipase, subjecting said sample with inactivated lipase to a purification step to from a HMW-depleted sample, and formulating said sample with at least one fatty acid ester, polysorbate 80 (claim 14), wherein the pharmaceutical composition has reduced lipase activity compared to a pharmaceutical composition not subjected to stress conditions, and wherein said reduced lipase activity is measured after a period of storage at long-term storage conditions. Dependent claims 5-6 are drawn to the stress condition being agitation from 50-500 rpm for 1-96 hours. Dependent claims 7-8 is drawn to the stress condition being heat stress from 25-60oC for 2 weeks to 5 years. And dependent claims 9-11 are drawn to purification steps comprising cation exchange and/or size exclusion chromatography.
The difference between the instant claims and the ‘626 claims is that the ‘626 claims recited “wherein said reduced lipase activity is measured after a period of storage at long-term storage conditions” and a time period for the heat stress treatment. However, they would still necessarily anticipate the instant claims, since such measurement could be done in the instant method claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
34. All claims are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CIARA A MCKNIGHT whose telephone number is (703)756-4791. The examiner can normally be reached M-F 8:00am-4:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath Rao can be reached on (571) 272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CIARA A MCKNIGHT/Examiner, Art Unit 1656
/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656
Prosecution Insights