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 .
Response to Amendment
Applicant’s arguments filed 12/12/2025 have been entered. Claims 1-24 are pending in the application, the 112(b) rejections previously set forth are withdrawn in view of the arguments and amendment.
Response to Arguments
Applicant's arguments filed 12/12/2025 have been fully considered but they are not persuasive.
In response to applicant’s argument that Shultz only evaluated acidic variant for adalimumab, Schultz teaches therapeutic proteins such as an antibodies examples of include omalizumab (0302), examiner notes a reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art see MPEP 2123. In response to applicant’s argument that Shultz’ variant are in the context of solid unit form, Schultz teaches a solid unit comprising a protein (abstract), the protein having (e.g. 98%, 99%, 99.5% or more) monomer (0115-0116), as discussed below.
In response to applicant’s argument that Shultz is not directed to the method of purification, Wong and Yang provide the recited method as discussed below, the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
Claim interpretation
The claims recite limitations including CEX-HPLC, HMW, SE-HPLC, interpreted as cation exchange chromatography, high molecular weight, and size exclusion chromatography, acronyms should be spelled out on first occurrence.
Priority
Acknowledgment is made of applicant's claim for foreign priority based on applications filed in IN on 05/01/2020. It is noted, however, that applicant has not filed a certified copy of application IN 2020/21018452 as required by 37 CFR 1.55.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 15-20, 23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Claim 15 recites a process for obtaining pharmaceutical purified composition of anti-IgE antibody as claims in claim 1 consisting of: a) loading the protein mixture onto an anion exchange resin with a buffer at pH selected from pH 7.5 to 7.5, it is unclear what is required by the term consisting of, and if there is support in the original disclosure for this limitation. The instant specification discloses on page 8, lines 24-28 “The term "comprises" or "comprising" is used in the present description, it does not exclude other elements or steps. For purpose of the present invention, the term "consisting of' is considered to be an optional embodiment, of the term "comprising of'. If hereinafter a group is defined to comprise at least a certain number of embodiments, this is also to be understood to disclose a group which optionally consists only of these embodiments”, this definition appears broader than ordinary meaning of consisting of, see MPEP 2111.03 for details on the use of transitional phrases.
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.
Claims 1-24 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 “wherein the purified composition of anti-IgE antibody is obtained from anion exchange resin, wherein the anion exchange is performed in flow-through mode; and wherein the anion exchange resin comprises a loading step and a washing step”, the language of resin comprising steps is unclear.
Claim 15 recites the limitations of a process for obtaining pharmaceutical purified composition of anti-IgE antibody as claims in claim 1 consisting of: a) loading the protein mixture onto an anion exchange resin with a buffer at pH selected from pH 7.5 to 7.5. This is unclear, the term the protein mixture lacks antecedent basis and it is unclear what the protein mixture comprises, or if the process begins from a culture, or after affinity chromatography as in the instant examples, further it is unclear what is required by the term consisting of, the instant specification discloses on page 8, lines 24-28 “The term "comprises" or "comprising" is used in the present description, it does not exclude other elements or steps. For purpose of the present invention, the term "consisting of' is considered to be an optional embodiment, of the term "comprising of'. If hereinafter a group is defined to comprise at least a certain number of embodiments, this is also to be understood to disclose a group which optionally consists only of these embodiments”, see 12(a) rejection above. The instant examples utilize steps of affinity chromatography and viral inactivation, it is unclear if this process is a more limited subset of the full process as described in the instant disclosure, or if the recited purity could be achieved without the other steps in the examples.
Additional claims are rejected as dependent on a rejected claim.
Double Patenting
Claims 1-14 of this application is patentably indistinct from claims 1-12 of Application No. 19/092,641. Pursuant to 37 CFR 1.78(f), when two or more applications filed by the same applicant or assignee contain patentably indistinct claims, elimination of such claims from all but one application may be required in the absence of good and sufficient reason for their retention during pendency in more than one application. Applicant is required to either cancel the patentably indistinct claims from all but one application or maintain a clear line of demarcation between the applications. See MPEP § 822.
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.
Claims 1-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 11, 12, 15-1714 of copending Application No. 19/092,641 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application requires a substantially pure composition of anti-lgE antibody omalizumab, with the recited acidic species, and purity. See 112(b) rejection with respect to HWM. Alternatively, the claims are obvious with respect to HMW in view of the rejections below.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-20 of this application is patentably indistinct from claim 30, 38-41, 45, 45, 48, 50-54 of Application No. 17/922,729. Pursuant to 37 CFR 1.78(f), when two or more applications filed by the same applicant or assignee contain patentably indistinct claims, elimination of such claims from all but one application may be required in the absence of good and sufficient reason for their retention during pendency in more than one application. Applicant is required to either cancel the patentably indistinct claims from all but one application or maintain a clear line of demarcation between the applications. See MPEP § 822.
Claims 1-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 30, 38-41, 45, 45, 48, 50-54 of copending Application No. 17/922,729 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application requires a substantially pure composition of anti-lgE antibody omalizumab: Instant claim 15 : Reverence claim 31, process with anion exchange in flow through; Instant claims 1-4 : Reference claim 31, 38, 50-52, acidic variants Instant claims 1, 4-8 : Reference claim 31, 53, 54 high molecular weight; Instant claims 13, 14 : Reference claim 41 Isoelectric point; Instant claims 9-14 : Reference claim 48 monomer purity
Claims 15- 20 are rejected as obvious over the reference application in view of the rejections below.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-20 of this application is patentably indistinct from claim 1, 10-14,22, 23, 27 ,28 ,37 of Application No. 17/922,734. Pursuant to 37 CFR 1.78(f), when two or more applications filed by the same applicant or assignee contain patentably indistinct claims, elimination of such claims from all but one application may be required in the absence of good and sufficient reason for their retention during pendency in more than one application. Applicant is required to either cancel the patentably indistinct claims from all but one application or maintain a clear line of demarcation between the applications. See MPEP § 822.
Claims 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 10-14,22, 23, 27 ,28 ,37 of copending Application No. 17/922,734 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the reference application requires a substantially pure composition of anti-lgE antibody omalizumab and process of purification:
Instant claim 1/15: Omalizumbab, reference claims 17, 37
Instant claims 1-4: acidic species, reference claims 23
Instant claims 1, 5-8, reference claims 37, 1, 27, 28
Instant claims 1, 4-8 : Reference claim 27, 28, 37 high molecular weight; Instant claims 13, 14 : Reference claim 10, 11 Isoelectric point; instant claims 15, -17, reference claims 12-14, buffer.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim Rejections - 35 USC § 103
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.
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) 1-12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schultz (US PG Pub 2016/0228371) in view of Wong (US PG Pub 2022/0203347).
With respect to claim 1, and 24, Schultz teaches formulations of stable compositions of a therapeutic agent (particularly a therapeutic protein such as an antibody, DVD-Ig protein, or peptide) and a stabilizer, referred to as solid units (abstract, 0001-0013), examples of antibodies include omalizumab (0302), in embodiments solid units comprising less than about 15% acidic species of the antibody (0074-0078, 0126), acidic species can be detected by various methods, such as, for example, WCX-10 HPLC (a weak cation exchange chromatography) (0254, 0611), lowering the amount of acidic species variants or process-related impurities (0276), compositions comprising stable therapeutic agents, and stability of the therapeutic agent is determined by a result of 90%, 95%, 98% or more monomer therapeutic agent (0030), the protein is considered stable if there is a low percentage of aggregates protein, or a high level (e.g. 98%, 99%, 99.5% or more) monomer (0115-0116), size exclusion chromatography (SEC) may be used to determine fragment and monomer (aggregation) content for protein, such as antibodies (0171, 0611, by SE-HPLC), monomer percentages may be described in terms of percent aggregate, including less than 1% aggregate (0173), low process related impurities refer to about 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, or less of process-related impurities, in embodiments a low process-related impurity composition is free of process-related impurities or is substantially free of process-related impurities (0255), less than 0.5% impurities. While Shultz does not use the term high molecular weight or HMW impurities, Shultz’ less than 0.5% impurities would inherently provide the recited limitation.
Alternatively, Wong teaches Wong teaches purification of antibodies including omalizumab (0019, 0070, 0233-0235, 0544), contaminants removed include variants (0083, 0211, 0238) and HMW, the amount of aggregated protein may be reduced by a number of ranges of 5% to about 99% (0216), analyzed by SEC (0564-0565), and methods of measuring are known in the art (0216, HMW is less than 0.5%), analyzed by SE-HPLC (0188-0189, 0565), examiner notes “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior art product was made by a different process”, In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). Further, “although produced by a different process, the burden shifts to applicant to come forward with evidence establishing an unobvious difference between the claimed product and the prior art product”, In re Marosi, 710 F.2d 798, 802, 218 USPQ 289, 292 (Fed. Cir. 1983). See MPEP 2113, in the interest of compact prosecution, Wong teaches purification of impurities using flow through anion exchange chromatography (0038-0049), and aggregated polypeptide can be high molecular weight (HMW) protein (0216). See 112(b) rejections above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that Shultz taught antibody would include HWM impurities as the use of anion exchange is known to reduce HWM impurities as shown by Wong, and the courts have held that combining prior art elements according to known methods to yield predictable results would have been obvious to a person of ordinary skill in the art before the filing date, see MPEP §2143.
Applicant amended to require: wherein the anion exchange resin comprises a loading step and a washing step. and wherein the loading step and the washing step is performed at the same pH,
As noted above, with respect to claim 1 and 24, the composition is taught by the combination of Schultz, examiner notes “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior art product was made by a different process”, In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). Further, “although produced by a different process, the burden shifts to applicant to come forward with evidence establishing an unobvious difference between the claimed product and the prior art product”, In re Marosi, 710 F.2d 798, 802, 218 USPQ 289, 292 (Fed. Cir. 1983). See MPEP 2113.
With respect to claims 2-4, 21, 22, the pharmaceutical purified composition of claim 1 is taught above. Shultz teaches embodiments with acidic variant about 12%, 11 %, 10%, 9%, 8%; examiner notes the instant specification discloses “The term “about”, as used herein, is intended to refer to ranges of approximately 10-20% greater than or less than the referenced value. In certain circumstances, one of skill in the art will recognize that, due to the nature of the referenced value, the term “about” can mean more or less than a 10-20% deviation from that value”, providing the acidic variant is about 12%, about 11 %, about 10%.
With respect to claims 5-8, the pharmaceutical purified composition of claim 1 is taught above. Schultz teaches Wong teaches HMW (0216, in embodiments HWM is less than about 5 ppm, less than about 3 ppm, less than about 2 ppm, less than about 1 ppm, reduction of aggregated protein may be reduced by between about any of 10% and 99%, 30% and 95%, 30% and 99%, 50% and 95%, 50% and 99%, 75% and 99%, or 85% and 99%. The amount of aggregated protein may be reduced by about any of 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% (0216), Schultz teaches 0.5%, or less of process-related impurities, in embodiments a low process-related impurity composition is free of process-related impurities or is substantially free of process-related impurities (0255) (HMW is less than 0.4%, less than 0.3%, HMW is less than 0.2%, less than 0.1%.
With respect to claims 9-11, the pharmaceutical purified composition of claim 1 is taught above. Examiner notes Instant specification page 8 lines 7-10 defines the term “substantially pure antibody” as including an antibody that is substantially free of HMW and acidic variants, less than 0.5% HMW impurities (p. 11 lines 15-17), and substantially pure monomer and less than 15% acidic species or variant (p.12 lines 29-31), 99% purity with HMW of 0.07% (p. 22 table 2), "substantially pure antibody" includes an antibody that is substantially free of HMW and acidic variants and specifically binds to IgE. Less than about 99% down to less than about 50% (p. 8 lines 7-12). Wong teaches HWM of less than about 1 ppm HMW (0216, in embodiments HWM is less than about 5 ppm, less than about 3 ppm, less than about 2 ppm, less than about 1 ppm, reduction of aggregated protein may be reduced by between about any of 10% and 99%, 30% and 95%, 30% and 99%, 50% and 95%, 50% and 99%, 75% and 99%, or 85% and 99%. The amount of aggregated protein may be reduced by about any of 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, 80%, 90%, or 95% (0216), Schultz teaches 0.5%, or less of process-related impurities, in embodiments a low process-related impurity composition is free of process-related impurities or is substantially free of process-related impurities (0255); 98%, 99%, or 99.5% or more of monomer protein (0115-0116), wherein the omalizumab is substantially pure having purity more than 90%, more than 94%, more than 98%.
With respect to claim 12, the pharmaceutical purified composition of claim 1 is taught above. Examiner notes “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior art product was made by a different process”, In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985). Further, “although produced by a different process, the burden shifts to applicant to come forward with evidence establishing an unobvious difference between the claimed product and the prior art product”, In re Marosi, 710 F.2d 798, 802, 218 USPQ 289, 292 (Fed. Cir. 1983). See MPEP 2113, in the interest of compact prosecution, Wong teaches wherein the anion exchange is POROS 50 HQ which is strong anion exchange (Wong 0185).
Claim(s) 13, 14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schultz (US PG Pub 2016/0228371) in view of Wong (US PG Pub 2022/0203347), with evidence from Degterev (Improvement of the Degradation Profiling of Eculizumab and Omalizumab Monoclonal Antibodies by Liquid Chromatography–Mass Spectrometry, 2021), and Weisbjerg (Serial Coupling of Ion-Exchange and Size-Exclusion Chromatography to Determine Aggregation Levels in mAbs in The Presence of a Proteinaceous Excipient, Recombinant Human Serum Albumin, 2014).
With respect to claims 13, 14, the pharmaceutical purified composition of claim 1 is taught above. Wong and Schultz each teach omalizumab, Wang teaches isoelectric points of about any of 6 to 10, 7 to 9, or 8 to 9, 6, 7, 7.5, 8, 8.5, 9, 9.5, or 10 (0229), pl selected from 7.5, 7.6, 7.7, and 7.9, is about 7.6.
Additionally, Weisbjerg and Degterev provide evidence omalizumab exhibits the recited pI: Weisbjerg teaches literature data for pI for Omalizumab is 7.0-7.6 (Table 1, p. 550, col 2) Degterev teaches pI of 7.35-7.45 (p. 1600, col 2), pI 7.5, 7.6, 7.7, and 7.9.
Claim(s) 15-18, 23 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schultz (US PG Pub 2016/0228371) in view of Wong (US PG Pub 2022/0203347), in view of Yang (US PG Pub 2023/0124565) with evidence from Sutter (US PG Pub 2021/0130396).
With respect to claims 15-18, (See 112(b) rejection above), the composition of claim 1 is taught above. Wong teaches methods of purifying an antibody from an impurity using ion exchange material (0009, 0014, 0018-0019, 0038, 0117-0123, 0165-0196), in embodiments the antibody is omalizumab (0019, 0235, 0544), a process for obtaining pharmaceutical purified composition of anti-IgE antibody wherein the anti-IgE antibody is omalizumab,
A portion of the process consisting of: step b) loading the composition on anion exchange chromatography material (a) loading the protein mixture onto an anion exchange resin (0038)), impurities preferentially bind to the resin while the product breakthrough is collected (0003, 0049, b) eluting the protein mixture in a flow through mode whereby product-related impurities bind to the anion exchange resin), c) collecting fractions comprising the polypeptide d) washing the anion exchange chromatography material with equilibration buffer (0038), washing the ion exchange material with the equilibration buffer (0009-0015, 0036-0045, 0115-0123, 0163-0179), in embodiments the wash buffer is the same as the load buffer (0206), in embodiments the pH of the equilibrium buffer is about 6-10, or any of 6.0, 6.5, 7.0, 7.5, 8.0, 8.5, 9.0, 9.5 or 10.0 (0135, 0149, using a buffer having the pH in the range of 7.0 to 7.5). Wong teaches antibodies including omalizumab and pH values which include the recited range, without showing unexpected results, the claimed pH cannot be considered critical. Accordingly, one of ordinary skill in the art before the effective filing date of the claimed invention would have optimized, by routine experimentation, the loading buffer pH in order that the protein to be purified does not bind (In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980)), since it has been held that where the general conditions of the claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art (In re Aller, 105 USPQ 223), and as evidenced by Sutter, Sutter teaches methods for purifying proteins (abstract), including omalizumab (0019), using anion exchange (0006-0009), and that the skilled person knows how to adapt the pH and/or the salt condition of the buffer in view of the pI (Isoelectric Point) of the protein to be purified in order that the protein to be purified does not bind (0057, 0068).
With respect to the limitations of claim 1 of the impurities of acidic variant and HWM variants, examiner notes "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.” Id. (quoting Minton v. Nat’l Ass’n 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." While the taught combination does not explicitly teach acidic variants in less than 15% and HMW variant is less than 0.5%, absent clarification of differences over the art, the recited values are considered inherent. In the interest of compact prosecution Wong teach purification of antibodies, contaminants removed include variants and aggregates or derivatives of the polypeptide (0083, 0211) and HMW (0216, 0564-0565, and high molecular weight (HMW) variant), analyzed by SE-HPLC (0188-0189, 0565), Wong teaches the amount of aggregated protein may be reduced by a number of ranges of 5% to about 99% (0216), analyzed by SEC (0564-0565)
Additionally, Wong and Shultz each teach purification of antibodies, Wong teaches antibodies with isoelectric points of 6 to 10, 7 to 9, or 8 to 9, 6, 7, 7.5, 8, 8.5, 9, 9.5, or 10 (0229), Shultz teaches examples of omalizumab and adalimumab (0078), Yang teaches methods of preparing and purifying high purity antibodies (abstract, 0001-0012), antibodies having an isoelectric point of 7-9 (0030), passing through an anion exchange column, and use of a buffer with a pH of 7.0-8.0, with an example of 7.5 (0018-0022, 0103-106, loading onto an anion exchange resin with a suitable buffer at suitable pH selected from a pH of 7.0 to 7.5); flow through (0104, 0163-0166), antibodies include adalimumab and all therapeutic antibodies typically used in the art (0030), and when a neutral pH buffer is used, antibodies with higher isoelectric points escape without being attached to the anion exchange resin (0104), high-purity and high-quality population of antibodies where the effective removal of acidic isomeric variants can be adjusted to a desired ratio (0023-0037, 0048).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use a neutral buffer, or buffer with pH of 7.0 to 7.5, as taught by Yang, as according to Yang a neutral pH buffer allows antibodies with higher isoelectric points escape without being attached to the anion exchange resin (0104).
With respect to claim 23 the process as claimed in claim 15, is taught above. The taught combination provides loading of anion exchange chromatography resin, absent evidence of criticality performed till loading volume, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to ensure the resin contacts the mixture.
Claim(s) 19,20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wong (US PG Pub 2022/0203347) in view of Schultz (US PG Pub 2016/0228371), in view of Yang (US PG Pub 2023/0124565), with evidence from Sutter (US PG Pub 2021/0130396), in view of Leiss (US PG Pub 2022/0194980).
With respect to claims 19 and 20, the process as claimed in claim 15, is taught above. Wong teaches antibody breakthrough is collected at the overload pool and concentration determined based on dilution, volume, path length (0562-0597)Schultz teaches acidic species elute before basic charge variants (0253, 0285) quantitation was based on the relative area percentage of detected peaks at 280 nm (0614), and Yang teaches peaks for acidic, main, and basic isomers (Table 3), figure 6 illustrates a peaks with respect to UV(mAU) and volume, purified anti IgE antibody is obtained through peak collection in anion exchange chromatography, while the taught combination does not explicitly teach wherein the peak collection is performed from 2.5AU/cm to about 1.5AU/cm, or the protein peak collection criteria selected from the ascending value of about 1.5AU/cm and ends at a descending value of about 1.5 AU/cm the selection of collection criteria would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention in order to collect the desired peak of effluent.
Alternatively, Leiss teaches purification of antibodies (0003), including omalizumab (0033) collection eluate initiated and terminated based on absorbance and volume (0348), and in an example collection at 2.5 AU/cm (table 11), while Leiss does not explicitly teach 2.5AU/cm to about 1.5AU/cm, or 1.5AU/cm, or the protein peak collection criteria selected from the ascending value of about 1.5AU/cm and ends at a descending value of about 1.5 AU/cm, as Leiss teaches eluate initiated and terminated based on absorbance and volume (0348) and a specific value of 2.5 au/cm, as the specification is silent to unexpected results, the specific peak collection value is not considered to confer patentability to the claims. As the peak is a variable that can be modified, among others, by adjusting dilution, the precise amount would have been considered a result effective variable by one having ordinary skill in the art before the effective filing date of the claimed invention. As such, without showing unexpected results, the claimed amount cannot be considered critical. Accordingly, one of ordinary skill in the art before the effective filing date of the claimed invention would have optimized, by routine experimentation, the peak collection to obtain the desired species (In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980)), since it has been held that where the general conditions of the claim are disclosed in the prior art, discovering the optimum or workable ranges involves only routine skill in the art (In re Aller, 105 USPQ 223).
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/JEANNIE MCDERMOTT/Examiner, Art Unit 1777
/BRADLEY R SPIES/ Primary Examiner, Art Unit 1777