DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 08/31/2026 has been entered.
Status of claim rejections
The objections to claim 29 is withdrawn in view of Applicant’s amendments to the claim in the response filed 08/31/2026.
The rejection of claims 2-4 under 35 USC 112(d) is withdrawn in view of Applicant’s cancellation of the claims in the response filed 08/31/2026.
The rejections under 35 USC 102/103 is maintained in view of Applicant’s arguments in the response filed 08/31/2026.
This Action is FINAL.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 08/31/2026 was filed after the mailing date of the Final Office Action on 07/31/2026. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Interpretation
The examiner has interpreted the claims as follows:
Instant claim 1 recites, “A composition consisting essentially of a biosimilar of omalizumab and product related impurities selected from basic variants (BV), and low molecular weight (LMW) species; wherein the composition is characterized by: (a) an average ratio of basic variants to the main peak of the biosimilar omalizumab of less than 0.09; and (b) an average ratio of LMW species to the main peak of the biosimilar of omalizumab of below about 0.00500; wherein the biosimilar of omalizumab in the composition has purity of at least 99.5% as determined by SE-HPLC and wherein the composition is a drug substance.” In the instant case, the examiner is interpreting the claims to encompass any composition having the claimed purities, even if the ratios are determined by a different method, as the claims are drawn to a composition comprising a biosimilar of omalizumab and a production related impurity (i.e., basic variants and/or low molecular weight species) and NOT a method of determining the purity of a biosimilar omalizumab product. Put simply, any biosimilar omalizumab composition that contains the claimed purities would qualify as prior art, regardless of the methods used to determine them. The rejections below reflect the examiner's interpretation. Please note that the dependent claims and new claims 24-28, also reciting the determination step are also interpreted in the same manner.
Further regarding claim 1, the transitional phrase “consisting essentially of” limits the scope of a claim to the specified materials or steps "and those that do not materially affect the basic and novel characteristic(s)" of the claimed invention. In re Herz, 537 F.2d 549, 551-52, 190 USPQ 461, 463 (CCPA 1976). For the purposes of searching for and applying prior art under 35 U.S.C. 102 and 103, absent a clear indication in the specification or claims of what the basic and novel characteristics actually are, "consisting essentially of" will be construed as equivalent to "comprising." (see MPEP 211.03).
Claims 20-22 recites, inter alia, “the average ratio of impurities to the main peak is determined from” (see claim 20-21), and “wherein the composition is produced by a process performed at large scale. . .” (see claim 22). These claims have also been interpreted as product-by-process limitations, as set forth above (see MPEP 2113).
Claim 29 recites “A composition consisting essentially of a biosimilar of omalizumab and product related impurities selected from basic variants (BV) and low molecular weight (LMW) species; wherein the composition is characterized by: (a) an average ratio of the basic variants to the main peak of the biosimilar of omalizumab of less than 0.09 or less; and (b) an average ratio of the LMW species to the main peak of the biosimilar of omalizumab of below about 0.00500; wherein, the basic variants is present in an amount of 8% or less, as determined by CEX- HPLC; wherein the biosimilar of omalizumab in the composition has purity of more than 84%, as determined by cation exchange high performance liquid chromatography (CEX-HPLC); wherein the composition is a drug substance.” The examiner is interpreting this claim in the same manner as claim 1. Please note that the same interpretation applies to dependent claims 30-33.
Maintained Claim Rejections - 35 USC § 102/103
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 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)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(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.
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, 6-14, 20-22 and 24-33 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Shenoy (US20180333493 A1), as evidenced by Wang1 and Wang2.
Please note that, as discussed above, claims 6-14, 20-22, and 24-28 are considered product-by-process limitations, such that the claimed composition requires only a biosimilar of omalizumab and the claimed impurities.
Shenoy teaches a pharmaceutically acceptable protein agent formulation comprising various monoclonal antibodies including omalizumab (XOLAIR®) and biosimilars for use in low viscosity formulations (a composition comprising a biosimilar of omalizumab as in claim 1 and 29; see paragraphs 0097, 0190, 0195, 0593, see also table on pg. 89).
Shenoy does not explicitly the teach the composition contains, e.g., basic variants with an average ratio of basic variants to main peak of less than 0.09 (see also claims 6-8) or that the omalizumab main peak purity is at least 99.5-99.9% (see claims 24-27). However, Wang1 evidences omalizumab charge variants (including basic variants) when analyzed using CEX-HPLC that shows the basic component was 8.2% ± 0.8%. As such, the recitation of “an average ratio of basic variants to the main peak of omalizumab of about less than 0.09” (claim 1), “0.06 or less” (claim 6), “0.05 or less” (claim 7), “0.04 or less” (claim 8) are met by the disclosure of Shenoy, absent evidence to the contrary (see MPEP 2112.01). Furthermore, the recitation of “the basic variants are present in an amount of about 7.5% or less, about 7.0% or less, about 6.5% or less, about 6.0% or less, about 5.5% or less, about 5.0% or less, about 4.5% or less, or about 3.5% or less, as determined by CEX-HPLC” (claim 30), “the biosimilar of omalizumab in the composition has purity of more than 84.5%, as determined by CEX-HPLC” (claim 31), “wherein the biosimilar of omalizumab in the composition has purity of more than 85%” (claim 32), and “the biosimilar of omalizumab in the composition has purity of more than 85.5%” (claim 33) are met by the disclosure of Shenoy, absent evidence to the contrary (see MPEP 2112.01).
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Shenoy does not explicitly teach the composition contains low molecular weight species impurities or average ratio of LMW below about 0.00480 (see claims 9-14) or present in 0.4% or less, 0.3% or less, about 0.2% or less, etc. (see claim 28). However, Wang2 evidences that monoclonal antibodies (mAbs) have been successfully employed to target a wide range of therapeutic areas over the last two decades and heterogeneity of antibodies is known in the art. For example, low molecular weight (LMW) species is an example of product-related impurities that contribute to the size heterogeneity of mAb products and can be measured using SEC chromatography methods and the LMW species include precursors, degradation products, truncated species, proteolytic fragments including Fab fragments, Fc or heavy chain fragments, ligand or receptor fragments, H2L (2 heavy chains and 1 light chain), H2 (2 heavy chains), HL (1 heavy chain and 1 light chain), HC (1 heavy chain), and LC (1 light chain) species (see pg.1 ; FIG. 8; pg. 5, pg. 9-10). Wang also evidences that these impurities can be in the range of 0.5-20%, low weight molecular species can be present at <1% relative abundance in mAb products (see pg. 25). As Wang2 evidences LMW impurities exist in mAb formulations % (like omalizumab or biosimilars; see pg. 14) at as low as <1%, absent evidence to the contrary, the omalizumab/biosimilar formulation of Shenoy contains low levels of LMW species impurities. Note that the recitation of the “average ratio of LMW species to main peak is below about 0.000480” (claim 9), “below about 0.00400” (claim 10), “below about 0.00300” (claim 11), “below about 0.00200” (claim 12), “below about 0.00100” (claim 13), “below about 0.00080” (claim 14) or “present in 0.4% or less, 0.3% or less, about 0.2% or less”, etc. (see claim 28), are met by the disclosure of Shenoy, absent evidence to the contrary (see MPEP 2112.01).
In the alternative, it would have been prima facie obvious to one of ordinary skill in the art to use the omalizumab biosimilar composition of Shenoy with a reasonable expectation of success. One of ordinary skill would have been motivated to use the composition because the composition of Shenoy provides high concentration formulations of therapeutic monoclonal antibodies like omalizumab or biosimilars for the therapeutic treatment of asthma, chronic idiopathic urticaria, and acute bronchospasm or status asthmatics (see paragraph 0659).
Further regarding claim 1, the biosimilar is a drug substance.
Accordingly, the claimed invention was anticipated, or in the alternative, prima facie obvious over the teachings of Shenoy.
Response to Arguments
On pg. 7 of the remarks, Applicant argues the rejection under 35 USC 102 regarding the Shenoy reference. Applicant argues that Shenoy’s primary objective is viscosity reduction in formulated drug products, distinct from the invention’s objective of achieving defined impurity ratios and impurity profile at the drug substance level. Applicant argues that the invention concerns compositions as a drug substance consisting of biosimilar omalizumab with improved purity and reduced impurities and that omalizumab is merely in a laundry list in Shenoy and no disclosure for the reduction of impurities and cannot anticipate the claims. Applicant argues that Wang1 and Wang2 does not anticipate the claims because they fail to disclose a composition disclosing impurity-to-main peak ratios as recited in the claims.
In response, the examiner disagrees. First, as discussed in the claim interpretation set forth above, the claims are drawn to a product, i.e., any composition having the claimed purities, even if the ratios are determined by a different method, as the claims are drawn to a composition comprising a biosimilar of omalizumab and a production related impurity (i.e., basic variants and low molecular weight species) and NOT a method of determining the purity of a biosimilar omalizumab product. Put simply, any biosimilar omalizumab composition that contains the claimed purities would qualify as prior art, regardless of the methods used to determine them. While Shenoy is directed to viscosity reducing formulations, Shenoy explicitly discloses a composition that can be omalizumab or a biosimilar of omalizumab, as discussed above. Furthermore, Shenoy does not have to disclose the reduction of impurities (i.e., a process) because the claims are drawn to a product, and not a process of reducing impurities, nor a process of measuring drug product-related impurities. Also, it is noted that both Wang1 and Wang2 are cited for evidentiary purposes, to show that omalizumab and omalizumab biosimilars contain the product related impurities (basic variants and low molecular weight species) in the claimed ranges as claimed by Applicant.
On pg. 8-10, Applicant argues the rejections under 35 US 103. Specifically, Applicant argues a PHOSITA would not refer to Shenoy because Shenoy only discloses reduction of viscosity in a drug formulation and does not describe a composition consisting of biosimilar omalizumab with a purity of 99.5% (or 84%) or describe a specific reduced impurity profile or impurity-to-main peak ratio. Applicant argues Shenoy teaches using Globucel ® and Herceptin® and Rituxan® to show reduced vicosity. Applicant argues a PHOSITA would have not have referred to Shenoy to prepare a biodsimilar drug having an increased purity profile and reduced levels of impurities because Shenoy is irrelevant to biosimilar omalizumab compositions. Applicant urges that Shenoy lists omalizumab in a laundry list of antibodies in the context of preparing formulations having reduced viscosity. Applicant further argues Wang 1 and 2 provide no teaching, suggestion, or motivation to prepare the claimed composition, and achieving all the attributes disclosed in the claim simultaneous is not taught or enabled by the reference. Applicant argues that Wang1 is directed to comparative characterization study of omalizumab and a biosimilar and KA has higher proportions of acidic and basic variants and lower purity, that the claims are directed to a product intended for human use where high purity and controlled impurity levels are critical to stability, immunogenicity, safety, and product costs. Applicant argues that the biosimilar of Wang1 fails to achieve high purity and fails to provide a reasonable expectation of success. Applicant then argues Wang2 is also irrelevant to a drug substance formulation of a biosimilar of omalizumab, merely includes generic disclosure that purification methodologies could reduce impurities and does not disclose or suggest the drug substance claimed.
In response, the examiner disagrees for much of the same reasons as set forth above. Shenoy explicitly discloses omalizumab and biosimilars in a composition (as discussed above). Second, neither of the Wang references are required to disclose any specific method of preparing the claimed composition because, as set forth above, the claims are not drawn to a process of preparing the omalizumab biosimilar, but rather the biosimilar product itself. Further, Wang 2 explicitly evidences “LMW species include precursors, degradation products, truncated species, proteolytic fragments including Fab fragments, Fc or heavy chain fragments, ligand or receptor fragments, H2L (2 heavy chains and 1 light chain), H2 (2 heavy chains), HL (1 heavy chain and 1 light chain), HC (1 heavy chain), and LC (1 light chain) species (see pg.1 ; FIG. 8; pg. 5, pg. 9-10). Wang also evidences that these impurities can be in the range of 0.5-20%, low weight molecular species can be present at <1% relative abundance in mAb products (see pg. 25). As Wang2 evidences LMW impurities exist in mAb formulations % (like omalizumab or biosimilars; see pg. 14) at as low as <1%, absent evidence to the contrary, the omalizumab/biosimilar formulation of Shenoy contains low levels of LMW species impurities. Furthermore, as interpreted above and as discussed above, the manner in which the purity is determined as argued is not relevant, as any biosimilar omalizumab composition that contains the claimed purities would qualify as prior art, regardless of the methods used to determine them. Thus, the rejections are maintained as set forth above.
Conclusion
NO CLAIMS ALLOWED.
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). 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 GEORGIANA C REGLAS whose telephone number is (571)270-0995. The examiner can normally be reached M-Th: 8:00am-2:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melenie Gordon can be reached at 571-272-8037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/G.C.R./Examiner, Art Unit 1651
/THOMAS J. VISONE/Supervisory Patent Examiner, Art Unit 1672
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