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 .
Response to Amendment
Applicant’s arguments filed 12/16/2025 have been entered. Claims 1-15 are pending in the application, rejections are withdrawn in view of the arguments and amendment. The 112(b) rejections and statutory double patenting rejection over co-pending application 17/722734 previously set forth are withdrawn in view of the amendment. Examiner acknowledges filing of the priority document.
Response to Arguments
Applicant's arguments filed 12/16/2025 have been fully considered but they are not persuasive.
In response to applicant’s argument that Wong primarily directed to resin regeneration and cleaning, Wong teaches methods of purifying a polypeptide from an impurity using ion exchange material (0009-0015, 0036-0045, 0115-0123, 0163-0179. In response to applicant’s arguments concerning Yang, see modified rejections below with evidence from Sutter and note 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). Wong teaches purification of antibodies, including omalizumab, with anion exchange, Yang teaches flow through anion exchange (0104, 0163-0166), antibodies include 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), the anion exchange column adsorbs cation-bearing proteins at the isoelectric point or higher, in the case of an antibody with an isoelectric point of 7 or higher, when a neutral pH buffer is used the antibody escapes to the flow through without being attached to the anion exchange resin (0164).
Specification
The use of the specific disclosed resins, which are trade names or 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 Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 12 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 1 and Claim 12 recite the limitation of wherein the antibody is Omalizumab. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Double Patenting
A rejection based on double patenting of the “same invention” type finds its support in the language of 35 U.S.C. 101 which states that “whoever invents or discovers any new and useful process... may obtain a patent therefor...” (Emphasis added). Thus, the term “same invention,” in this context, means an invention drawn to identical subject matter. See Miller v. Eagle Mfg. Co., 151 U.S. 186 (1894); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Ockert, 245 F.2d 467, 114 USPQ 330 (CCPA 1957).
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.
Claim 1-15 of this application is patentably indistinct from claim 6-20, 27-31 of Application No. 17/922734. 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 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7-17, 19-20, 22-31 of copending Application No. 17/922734 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the reference claims recite a substantially similar process comprising purification of an antibody or fusion protein with a pI of 7-8, and high molecular weight impurity, using Protein A or G affinity chromatography (instant claim 1, reference claims 21, 27), viral inactivation (instant claim 1, reference claims 1, 27), anion exchange with a pH 7-7.5 buffer (instant claim 1, reference claims 1, 27), specific HMW (instant claims 1-4, reference claims 27, 28), HWM reduction (instant claims 6-8, reference claims 7-9), pI, IgE, omalizumbab (instant claims 1, 10-12, reference claims 10, 11, 16, 17), buffer (instant claim 13, reference claim 15), resin (instant claim 14, 15, reference claim 19, 20).
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.
Claims 1-15 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wong (US PG Pub 2022/0203347), with evidence from Sutter (US PG Pub 2021/0130396) and Yang, in view of Yang (US PG Pub 2023/0124565).
With respect to claim 1, Wong teaches purifying polypeptides, in embodiments the polypeptide is an antibody (0019), the pI of the polypeptide may be about any of 6 to 10, 7 to 9, or 8 to 9 In some embodiments, the polypeptide has a pi of about any of 6, 7, 7.5, 8, 8.5, 9, 9.5, or 10 (0229, pl of 7 to 8), purifying a polypeptide from a composition comprising the polypeptide and an impurity using an anion exchange chromatography material (0038, a process of purifying an antibody or fusion protein with pI of 7 to 8 from a protein mixture comprising antibody or fusion protein), contaminants removed include variants and aggregates or derivatives of the polypeptide (0083, 0211) and HMW (0216, 0564-0565, and high molecular weight (HMW) impurity), analyzed by SE-HPLC (0188-0189, 0565), using ion exchange chromatography, in embodiments the ion exchange is anion exchange (0014, 0018, 0117-0123, 0165-0196), in embodiments using affinity chromatography including Protein A, Protein G prior to ion exchange chromatography (0020), in embodiments the antibody is omalizumab (0019, 0235, 0544), loading the composition on the ion exchange chromatography material (0010), wherein the load density exceeds the dynamic binding capacity of the ion exchange chromatography for the polypeptide; c) collecting fractions comprising the polypeptide (0010-0014, 0117-0123, loading the protein mixture obtained from step (b) onto anion exchange resin), impurities preferentially bind to the resin while the product breakthrough is collected (0003, 0049, eluting the protein mixture in a flow-through mode whereby HMW impurity binds to the anion exchange resin).
Wong teaches methods of purifying a polypeptide from an impurity using ion exchange material comprising equilibrating with an equilibration buffer, loading on the ion exchange material, collecting fractions, 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 the recited protein 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 Protein A chromatography followed by chromatography including 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).
Addtionally, Yang teaches methods of preparing and purifying high purity antibodies (abstract, 0001-0012), antibodies having an isoelectric point of 7-9 (0030), where the anion serves to exchange a specific anion in an aqueous solution with its own anion and the antibody escapes without being attached to the anion exchange resin when a neutral pH buffer is used, but impurities including with a low isoelectric point may be removed while being adsorbed onto the anion exchange resin, 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 anion exchange (0104, 0163-0166), antibodies include 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), the anion exchange column adsorbs cation-bearing proteins at the isoelectric point or higher, in the case of an antibody with an isoelectric point of 7 or higher, when a neutral pH buffer is used the antibody escapes to the flow through without being attached to the anion exchange resin (0164).
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 modify Wong's taught method to include Yang's method neutral buffer allows antibodies to escape to the flow through without being attached to the anion exchange resin and a buffer with pH of 7.0 to 7.5, into Wong's taught method, in order to allow antibodies with a higher isoelectric point to escape without being attached to the anion exchange resin (Yang 0104, 0164).
Wong teaches in examples virus inactivation prior to Protein A (0192), after anion exchange (0191, 0193), not specifically b) Subjecting the protein mixture obtained from affinity chromatography to viral inactivation. Yang teaches a similar system as discussed above, and steps of virus inactivation before and after anion exchange (0012, 0085-0090), and between chromatography steps (0128), such that it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to subject the protein mixture obtained from affinity chromatography to viral inactivation, as a matter of design choice in view of Yang, as Yang teaches virus inactivation between chromatography steps, and selection of any order of performing process steps is prima facie obvious in the absence of new or unexpected results (see MPEP 2144.04 IV. C), in the absence of new or unexpected results.
With respect to the limitations of wherein the eluted protein mixture obtained in step (d) comprises substantially pure monomer of the antibody or fusion protein and less than 0.5% of HMW impurity analyzed by Size Exclusion High-Performance Liquid Chromatography (SE-HPLC) Analysis, Wong and Yang teach purification of antibodies, 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) Yang teaches in embodiments antibodies purified with a high purity of 99.9%, and a prepared population of antibodies containing the residual DNA and the host cell protein at a concentration of 0.1 ppb and 5 ppm or less, respectively (0117). 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 the HMW impurity is less than 0.5%, absent clarification of differences over the art, the recited values are considered inherent.
With respect to claims 2-4, the process of purifying an antibody or fusion protein with pI of 7 to 8 from the protein mixture as claimed in claim 1, is taught above. As noted above, Wong and Yang teach purification of antibodies, 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); Yang teaches in embodiments antibodies purified with a high purity of 99.9%, and a prepared population of antibodies containing the residual DNA and the host cell protein at a concentration of 0.1 ppb and 5 ppm or less, respectively (0117). 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 the HMW impurity is less than 0.4%, less than 0.3%, less than 0.2%, less than 0.1%, absent clarification of differences over the art, the recited values are considered inherent.
With respect to claims 6-8 the process of purifying an antibody or fusion protein with p1 of 7 to 8from the protein mixture as claimed in claim 1, is taught above. 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) wherein HMW reduced by at least 80% analyzed by Size Exclusion High- Performance Liquid Chromatography (SE-HPLC) Analysis, HMW reduced by at least 90%, HMW reduced by at least 95%.
With respect to claims 9 and 10, the process of purifying an antibody or fusion protein with pI of 7 to 8 from the protein mixture as claimed in claim 1, is taught above. Wong teaches omalizumab (0019, 0235, 0544), and 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), the antibody or fusion protein has pI selected from 7.5, 7.6, 7.7, and 7.9, the antibody or fusion protein has pI 7.6).
With respect to claims 11 and 12, the process of purifying an antibody or fusion protein with pI of 7 to 8 from the protein mixture as claimed in claim 1 is taught above. Wong teaches omalizumab and IgE (0019, 0235, 0543-0544), wherein the antibody is capable to bind to IgE, the antibody is Omalizumab.
With respect to claim 13, the process of purifying an antibody or fusion protein with pl of 7 to 8
from the protein mixture as claimed in claim 1, is taught above. The taught combination teaches a buffer
as discussed above, Yang teaches Tris-HCL (0106, 0165-0167, buffer is selected from Sodium Phosphate, Tris-HCI, HEPES, Glycine-NaOH, and Tris-Acetate).
With respect to claims 14 and 15, the process of purifying an antibody or fusion protein with pI of 7 to 8 from the protein mixture as claimed in claim 1, is taught above. Wong teaches anion exchange materials known in the art and include, but are not limited to Poros™ HQ 50 (0185), wherein the anion exchange is a strong anion exchange, is POROS 50 HQ.
Claim 13 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wong (US PG Pub 2022/0203347), with evidence from Sutter (US PG Pub 2021/0130396) and Yang, in view of Yang (US PG Pub 2023/0124565), in view of Sutter.
With respect to claim 13, the process of purifying an antibody or fusion protein with p1 of 7 to 8 from the protein mixture as claimed in claim 1, is taught above. The taught combination teaches a buffer as discussed above, Sutter teaches a similar system as discussed above and that buffers include but are not limited to phosphate buffers, Tris buffers including sodium phosphate (0053, 0057), Yang teaches Tris-HCL (0106, 0165-0167, buffer is selected from Sodium Phosphate, Tris-HCl, HEPES, Glycine-NaOH, and Tris-Acetate). 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 sodium phosphate buffer as taught by Sutter as sodium phosphate is known in the art as a loading buffer in methods to purify omalizumab 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.
Conclusion
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANNIE MCDERMOTT whose telephone number is (571)272-4479. The examiner can normally be reached Monday - Friday 8:30 - 5:00 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vickie Kim can be reached at 571-272-0579. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JEANNIE MCDERMOTT/Examiner, Art Unit 1777
/BRADLEY R SPIES/ Primary Examiner, Art Unit 1777