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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06/18/2026 has been entered claims 1, 7-17, 19-20, 22-31 and 34-46 are pending in the application, the 112(b) rejections previously set forth are withdrawn in view of the arguments and amendment.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 06/18/2026 have been fully considered but they are partially persuasive.
Applicant’s arguments with respect to the 112 rejections are persuasive.
Applicant’s arguments have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Claim Rejections - 35 USC § 112
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 1,7-17,19, 20, 23 and 27-31, 34-46 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.
The term “suitable” in claims 1, 15, 22, 27 is a relative term which renders the claim indefinite. The term “suitable” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 40 recites wherein the eluted protein mixture is collected about 2.5AU/cm to about I.SAU/cm, claim 40 depends from claim 1, which recites a method consisting of specific steps, claim 40 is specific to a step of collecting which is not recited in claim 1, claim 1 excludes any element, step, or ingredient not specified in the claim, see MPEP 2111.03.
Additional claims are rejected as dependent on a rejected claim.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim Rejections - 35 USC § 103
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, 7-14, 16, 17, 19-20, 27-31, 34-46 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bonnerjea (US PG Pub 2006/0194953), with evidence from Shamashkin (A Tandem Laboratory Scale Protein Purification Process Using Protein A Affinity and Anion Exchange Chromatography Operated in a Weak Partitioning Mode, 2013), alternatively in veiw of Leber (US PG Pub 2017/0305999).
With respect to claim 1, Bonnerjea teaches antibody purification by Protein A and ion exchange, preferably anion exchange (0020, 0070, a process of purifying an antibody or a fusion protein, affinity chromatography Protein A or Protein G and anion exchange), the antibody a monoclonal antibody that has an isoelectric point (pI) which is at least 6.5 or above, more preferably is 7.0 or above, most preferably has an pI of at least 7.5 (0027, a protein with a pI of 7.5 to 7.9), the pH of buffer used for loading and running the first ion exchanger in a flow-through mode, the pH of the equilibration/loading buffer is preferably in the range of pH 6.5 to pH 9.0 (0028-0029, a buffer at a pH of 7.0 to 7.5), Protein A followed by virus inactivation, neutralization, and filtration (0057-0058. 0089, the protein mixture obtained from step (a) to a viral inactivation, a neutralization, and a filtration), the antibody collected in the including about one column volume of wash with the same equilibration buffer (0031, 0070, washing the anion exchange resin), the method provides at least 70%, more preferably at least 80%, most preferably at least 90% of the antibody loaded onto the first ion exchanger can be recovered in the flow-through of the ion-exchanger (0026, a substantially pure monomer).
With respect to the limitations of purity, and specific impurities, 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." Absent clarification of differences over the art, the recited impurities and purity are considered inherent. In the interest of compact prosecution, Shamashkin teaches a similar method of protein purification using Protein A and anion exchange and virus filtration (abstract) where the anion exchange is formulated to promote retention of impurities such as HMW species (p.3) and where the percent HMW was determined by SE-HPLC (Analytics, p. 4-6, Fig. 3), providing evidence that Bonnerjea’s taught method would provide HMW impurity reduction, or at least would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Alternatively, in the interest of compact prosecution, Leber teaches culturing of antibodies (abstract), and purification by standard techniques including protein A and anion exchange chromatography (0092), by a process which reduces the amounts of acidic or basic variants, and/or high and low molecular weight species (abstract) and reduction of percentage of high molecular weight species produced by the media by any of about 1%-100% (0078), and/or the percentage of acidic species by about 1-100% relative to media produced by a different method, and measurement of species by any known means in the art including ion exchange HPLC, size exclusion chromatography (0092, 0105, 0115). Such that it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that Bonnerjea’s process would include high molecular weight impurities and acidic variants as shown by Leber, additionally, Shamashkin teaches percent HMW was determined by SE-HPLC and the AEX resin improved removal of HMW (Analytics, p. 4, 7), providing evidence that Bonnerjea’s taught method would provide HMW impurity reduction.
With respect to claims 7-9, 23-26, 28-31, 44, Bonnerjea teaches the recited steps of purification of antibodies as discussed above. With respect to the limitations of the specific reductions in impurities, 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." Absent clarification of differences over the art, the recited impurities are considered inherent.
Alternatively, in the interest of compact prosecution, Leber teaches culturing of antibodies (abstract), and purification by standard techniques including protein A and anion exchange chromatography (0092), by a process which reduces the amounts of acidic or basic variants, and/or high and low molecular weight species (abstract) and reduction of percentage of high molecular weight species produced by the media by any of about 1%-100% (0078), and/or the percentage of acidic species by about 1-100% relative to media produced by a different method, and measurement of species by any known means in the art including ion exchange HPLC, size exclusion chromatography (0092, 0105, 0115). Such that it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention that Bonnerjea’s process would include high molecular weight impurities and acidic variants as shown by Leber, additionally, Shamashkin teaches percent HMW was determined by SE-HPLC and the AEX resin improved removal of HMW (Analytics, p. 4, 7), providing evidence that Bonnerjea’s taught method would provide HMW impurity reduction.
With respect to claims 10-11, the process according to claim 1, is taught above. Bonnerjea teaches the antibody may have a pI a monoclonal antibody that has an isoelectric point (pI) which is more preferably 7.0 or above, most preferably has a pI of at least 7.5 (0027, with a pI selected from 7.5, 7.6, 7.7, and 7.9, about 7.6).
With respect to claim 12-14, the process according to claim 1, is taught above. Bonnerjea teaches pH pH 6.5 to pH 9.0 as discussed above (0028-0029), and for a given application, the pH of the loading buffer might need finetuning for optimal discrimination of binding and non-binding for a given pair of antibody and contaminant protein A having differing pI values and different content, 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 fine tune the pH to wherein the buffer has a pH selected from 7.0, 7.1, 7.2, 7.3, 7.4, and 7.5, depending on the pI and contaminant to be removed.
With respect to claim 15, The process according to claim 1, is taught above. Bonnerjea teaches wherein the suitable buffer is selected from Sodium Phosphate, Tris- HCl, HEPES, Glycine-NaOH, and Tris-Acetate (0029, 0070-0078, 0082).
With respect to claim 19, The process according to claim 1, is taught above. Bonnerjea teaches the anion exchange is a strong anion exchange (0020).
With respect to claim 20, The process according to claim 19, is taught above. Bonnerjea teaches the strong anion exchange resin is functionalized with quaternized polyethyleneimine groups. (0020, 0027-0030).
With respect to claim 34, The process according to claim 1, is taught above. Bonnerjea teaches the recited process, and is silent as to the need for a Hydroxyapatite, a Hydrophobic interaction chromatography, and a multimodal chromatograph.
With respect to claim 38, the process according to claim 1, is taught above. Bonnerjea teaches the loading or equilibration buffer for the first anion exchange step has a conductivity 0.5-5 mS/cm, more preferably of from 1-3 mS/cm, most preferably of from 1.25-2.5 mS/cm, ideally, about 2 mS/cm (0029, the loading buffer conductivity is from about 1.5 mS/cm to about 3.5 mS/cm, 2.6mS/cm).
With respect to claims 41-43, Bonnerjea teaches the recited steps of purification of antibodies as discussed above. With respect to the limitations of the obtained peak, 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." Absent clarification of differences over the art, the recited obtained peaks are considered inherent.
With respect to claim 45, the process according to claim 1, is taught above. Bonnerjea teaches the antibody collected in the including about one column volume of wash with the same equilibration buffer (0031, 0070) and a post load wash (0070-0092, wherein the anion exchange chromatography resin is washed post obtaining the eluted protein mixture).
With respect to claim 46, the process according to claim 1, is taught above. Bonnerjea teaches loading operation including about one column volume of wash with the same equilibration buffer (0031 wherein the washing and loading step is performed at same pH).
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Bonnerjea (US PG Pub 2006/0194953), with evidence from Shamashkin (A Tandem Laboratory Scale Protein Purification Process Using Protein A Affinity and Anion Exchange Chromatography Operated in a Weak Partitioning Mode, 2013), alternatively in view of Leber, in view of Degterev (Improvement of the Degradation Profiling of Eculizumab and Omalizumab Monoclonal Antibodies by Liquid Chromatography–Mass Spectrometry, 2021), 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), and Leber (US PG Pub 2017/0305999).
With respect to claim 16, the process according to claim 1, is taught above. Bonnerjea teaches purifying monoclonal antibodies with a pI of at least 6.5 or above, more preferably is 7.0 or above, most preferably has a pI of at least 7.5 or above (0027), but does not teach the antibody is capable of binding to an lgE, or the antibody is Omalizumab.
Weisbjerg and Degterev teach 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). Additionally, Leber teaches culturing and purification of antibodies (abstract, 0092), specifically including monoclonal antibodies, IgE, and omalizumab (0012-0015), and purification by standard techniques including Protein A and anion exchange chromatography (0092), 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 use Bonnerjea’s taught process to purify Omalizumab, an IgE antibody, as Bonnerjea teaches purification of monoclonal antibodies with pIs of at least 6.5, and as shown by Degterev, Weisberg, Omalizumab is an antibody with a pI in that range, and according to Leber, omalizumab is known to be purified by similar processes.
Claims 23-26 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bonnerjea (US PG Pub 2006/0194953), with evidence from Shamashkin (A Tandem Laboratory Scale Protein Purification Process Using Protein A Affinity and Anion Exchange Chromatography Operated in a Weak Partitioning Mode, 2013), alternatively in view of Leber, with evidence from Ramasubramanyan (US PG Pub 2013/0338344).
With respect to claims 22-26, Bonnerjea teaches the recited steps of purification of antibodies as discussed above. With respect to the limitations of the specific reductions in impurities, 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." Absent clarification of differences over the art, the recited impurities are considered inherent. Leber teaches acidic species as discussed above. In the interest of compact prosecution, Protein purification and control of charge variants, aggregates (abstract) including acidic species (AR) using a loading pH of about 7-8.2, (0001-0019), including Protein A followed by anion exchange, and that the method can be used to selectively remove, significantly reduce, or essentially remove all of AR charge variants (0126-00138), the AR levels analyzed by cation exchange (0003, 0225), providing evidence that Bonnerjea’s taught method would reduce acidic species.
Claim 40 is rejected under 35 U.S.C. 103 as being unpatentable over Bonnerjea (US PG Pub 2006/0194953), with evidence from Shamashkin (A Tandem Laboratory Scale Protein Purification Process Using Protein A Affinity and Anion Exchange Chromatography Operated in a Weak Partitioning Mode, 2013), alternatively in view of Leber, in view of Leiss (US PG Pub 2022/0194980).
With respect to claim 40, the process according to claim 1, is taught above. Bonnerjea does not teach collection at 2.5AU/cm to about 1.5AU/cm. See 112 rejection above. 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, 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
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Coffman US 2013/0317198
Brown US 2012/0122759
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dieterle can be reached at 571 270-7872. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/JEANNIE MCDERMOTT/Examiner, Art Unit 1776
/BRADLEY R SPIES/ Primary Examiner, Art Unit 1776
Prosecution Insights