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 .
Applicant’s election without traverse of the species of a pharmaceutical composition comprising omalizumab and 2.4% or less of the 2H1L variant, as determined by capillary electrophoresis sodium dodecyl sulfate (CE-SDS), wherein the purity of omalizumab in the pharmaceutical composition is at least 96%, as determined by CE-SDS, in the reply filed on 02/09/2026 is acknowledged. Upon further consideration after search and consideration of the claims, the Examiner has withdrawn the species election.
Claims 1-28 are under consideration for their full scope. Claims 1-3 are independent claims.
Applicant’s IDS documents filed on 07/28/2025 and 02/09/2026 have been considered.
Claim Objections
Claims 1-3 are objected to because of the following informalities: the term omalizumab is capitalized in claims 1-3 and not capitalized in the rest of the claims. The term is the generic name for the antibody so it should properly not be capitalized
Appropriate correction is required.
6. 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.
7. Claims rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 12,378,282 (PTO-892; Reference A). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-8 of U.S. Patent 12,378,282 are directed to compositions which are indistinguishable from the pharmaceutical compositions of instant claims 1-28.
The reference teachings anticipate the claimed invention.
8. Claims rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 12,435,106 (PTO-892; Reference B). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-29 of U.S. Patent 12,435,106 are directed to methods of producing compositions which are indistinguishable from the pharmaceutical compositions of instant claims 1-28.
The reference teachings anticipate the claimed invention.
9. Claims rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 12,139,510 (PTO-892; Reference C). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-21 of U.S. Patent 12,139,510 are directed to methods of producing compositions which are indistinguishable from the pharmaceutical compositions of instant claims 1-28.
The reference teachings anticipate the claimed invention.
10. Claims 1-16, 22-23 and 25-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 40 and 42 of copending Application No. 17/682,314 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 40 and 42 of copending Application No. 17/682,314 are directed to compositions which are indistinguishable from the pharmaceutical compositions of instant claims 1-28.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
11. Claims 1-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 31, 33-40 and 43-55 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 claims 31, 33-40 and 43-55 of copending Application No. 17/922,729 are directed to compositions which are indistinguishable from the pharmaceutical compositions of instant claims 1-28 and methods of producing compositions which are indistinguishable from the pharmaceutical compositions of instant claims 1-28
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
12. Claims 1-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7-17 and 19-37 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 claims 1, 7-17 and 19-37 of copending Application No. 17/922,734 are directed to compositions which are indistinguishable from the pharmaceutical compositions of instant claims 1-28 and methods of producing compositions which are indistinguishable from the pharmaceutical compositions of instant claims 1-28
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
13. Claims 1-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of copending Application No. 17/928,101 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-22 of copending Application No. 17/928,101 are directed to compositions which are indistinguishable from the pharmaceutical compositions of instant claims 1-28 and methods of producing compositions which are indistinguishable from the pharmaceutical compositions of instant claims 1-28
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
14. Claims 1-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 43-48 of copending Application No. 18/620,441 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 43-48 of copending Application No. 18/620,441 are directed to compositions which are indistinguishable from the pharmaceutical compositions of instant claims 1-28 and methods of producing compositions which are indistinguishable from the pharmaceutical compositions of instant claims 1-28
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
15. Claims 1-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of copending Application No. 19/432,924 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-23 of copending Application No. 19/432,924 are directed to compositions which are indistinguishable from the pharmaceutical compositions of instant claims 1-28 produced by methods of producing compositions which are indistinguishable from those which produce the pharmaceutical compositions of instant claims 1-28
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
16. 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.
17. Claims 1-28 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.
Claims 1-3 do not recite what is meant by the abbreviations LC, HC, HH and 2H1L
The specification on page 2, lines 1-2 and 9-10 discloses the term “low molecular weight aggregates (LMWs)” but the claim recites “low molecular weight species (LMWs)” using the same abbreviation in claims 1 and 2 and “low molecular weights (LMWs) using the same abbreviation in claims 3 and 13-16. It is unclear what is encompassed by these terms in the claims.
The specification on pages 11-12, the specification discloses:
“The term "substantially pure antibody" used herein includes an antibody that is substantially free of impurity selected from product or process related impurity. In certain embodiment antibody is free of acidic variant, basic variant, low molecular weight and high molecular weight, substantially pure antibody has purity less than about 99% or less than about 98% or less than about 97% or less than about 95% or less than about 92% or less than about 90% or less than about 88% or less than about 85% or less than about 82% less than about 80% or less than about 75% or less than about 70% or less than about 65% or less than about 60% or less than 50%.”
“The term used "Size variants" refers to LMW, HMW, or aggregates.”
“The term used "low molecular weight" or "LMW" species which is a protein backbone-truncated fragments & considered as product-related impurities that contribute to the size heterogeneity of antibody. LMW species often have low or substantially reduced activity relative to the monomeric form of the antibody and can lead to immunogenicity or potentially impact pharmacokinetic properties in vivo. As a result, LMW species are considered critical quality attributes that are routinely monitored during drug development and as part of release testing of purified drug product during manufacturing. The LMW has molecular weight selected from 23kDa, 24kDa, 25kDa, 26kDa, 30kDa, 35kDa, 40kDa, 45kDa, 50kDa, 55kDa, 60kDa, 65kDa, 70kDa, 75kDa, 80kDa, 85kDa, 90kDa, 95kDa, 100kDa, 105kDa, 110kDa, 115kDa, 120kDa, 125kDa, 126kDa, and 127kDa. In certain embodiment the LMW is selected from LC, HC, HH, and 2HL1. The term "Light Chain" or "LC" of an antibody having a weight of 25 kDa is light or L chain. A typical antibody contains two light chain, lambda () and kappa (k). An antibody either has к chains or λ chains, never one of each. There is no functional difference has been found between antibodies having r or K light chains, and either type of light chain can be found in antibodies of any of the five major classes. The ratio of the two types of light chain varies from species to species. However, sometime protein mixture comprises only one LC which is considered LMW impurity.
The term "Heavy Chain" or "HC" of an antibody having a weight of 50 kDa each is a heavy or H chain. There are several different types of heavy chain that define the class or isotype of an antibody. These heavy chain types vary between different animals. The heavy chains contain a series of immunoglobulin domains with one variable domain (VH) for binding an antigen and constant domains (CH1, CH2, etc.). The heavy chains with α and γ have approximately 450 amino acids and the heavy chains with µ and ε have approximately 550 amino acids. However, sometime protein mixture comprises only one HC which is considered LMW impurity.
The term "Two Heavy One Light Chain" or "2H1L" or "H2L" in antibody species possess a single light chain. The 2H1L species of antibody forms due to the ß-elimination of a heavy chain cysteine residue, forming the inter-heavy and light chain disulfide bond, that leads to the formation of H2L species.
It is unclear what is encompassed by the terms “one or more variants”, low molecular weight species, low molecular weights, basic variants, LC, HC, HH, 2H1L, LC variant, HC variant, HH variant and 2H1L variant. These definitions in the specification are not limited to “one or more variants”, low molecular weight species, low molecular weights, basic variants, LC, HC, HH and 2H1L of Omalizumab and that needs to be clear in the claims.
It is unclear what is meant by the term “purity of omalizumab” particularly when read in the light of the recitation “wherein the basic variants are present in any amount of 10.80% or less” in claim 3. How can the purity of omalizumab be 96% with 10.8% basic variants. The specification specifically teaches that the purity of the composition is related to the removal of impurities of which the basic variants are one. “In an embodiment, the present invention provides simple, scalable, CHT process to remove at least one impurity selected from LMW, and basic variant, by using phosphate elution gradient without using NaCl, CaCl2, or any other additives.” (In particular, specification on page 3, lines 1-3, pages 11-12, whole document). Taken a step further it also becomes unclear whether the compositions of claims 1-2 and claims dependent thereupon may also include acid and/or basic variants or if the only variants permissible in the composition are LC, HC, HH, 2H1L and combinations thereof. It is unclear whether or not the term omalizumab is limited to the antibody with no acidic variants thereof, no basic variants thereof and no size variants thereof.
Correction is required.
18. 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.
Independent claims 1-3 are directed to:
1. A pharmaceutical composition comprising Omalizumab and one or more variants, wherein the one or more variant(s) are low-molecular-weight-species (LMWs) selected from LC, HC, HH, and 2H1L, wherein the 2H1L variant is present in an amount of 2.4% or less determined by capillary electrophoresis sodium dodecyl sulfate (CE- SDS); wherein the purity of Omalizumab in the composition is at least 96%, as determined by CE-SDS.
2. A pharmaceutical composition comprising Omalizumab and one or more variants, wherein the one or more variant(s) are low-molecular-weight-species (LMWs) selected from LC, HC, HH, and 2H1L, wherein the HC variant is present in an amount of 0.3% or less determined by capillary electrophoresis sodium dodecyl sulfate (CE-SDS);wherein the purity of Omalizumab in the composition is at least 96%, as determined by CE-SDS.
3. A pharmaceutical composition comprising Omalizumab and one or more variants, wherein the variant(s) are selected from low-molecular-weights (LMWs) and basic variant(s) wherein the low-molecular-weights (LMWs) are present in an amount of 0.4% or less determined by size exclusion-high performance liquid chromatography (SE- HPLC); wherein the basic variant(s) are present in an amount of 10.80% or less determined by cation exchange high performance liquid chromatography (CEX-HPLC);wherein the purity of Omalizumab is more than 96%, as determined by SE-HPLC; wherein the process is performed at large scale at 200L.
19. Claims 1-12, 22-23 and 25-28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by the XOLAIR® (omalizumab) product insert (IDS filed on 02/09/2026; Reference C6) as evidenced by Sutton et al. (PTO-892; Reference U) and Wang et al. (IDS filed on 02/09/2026; Reference C4).
The omalizumab product catalog teaches on page 1:
XOLAIR® (omalizumab) injection, for subcutaneous use XOLAIR® (omalizumab) for injection, for subcutaneous use
Initial U.S. Approval: 2003
The omalizumab product catalog teaches on pages 20-21:
Omalizumab is a recombinant DNA-derived humanized IgG1κ monoclonal antibody that selectively binds to human immunoglobulin E (IgE). The antibody has a molecular weight of approximately 149 kiloDaltons. XOLAIR is produced by a Chinese hamster ovary cell suspension culture.
XOLAIR (omalizumab) is administered as a subcutaneous (SC) injection and is available in prefilled syringe, autoinjector and in vials.
XOLAIR Injection (Prefilled Syringe or Autoinjector) XOLAIR (omalizumab) injection is supplied as a sterile, preservative-free, clear to slightly opalescent and colorless to pale brownish-yellow solution for subcutaneous injection.
XOLAIR (omalizumab) injection is available as a single-dose prefilled syringe or a singledose autoinjector.
Each 75 mg prefilled syringe or autoinjector delivers 75 mg omalizumab in 0.5 mL and contains arginine hydrochloride (21.05 mg), histidine (0.68 mg), L-histidine hydrochloride monohydrate (1.17 mg), and polysorbate 20 (0.2 mg) in Sterile Water for Injection (SWFI), USP.
Each 150 mg prefilled syringe or autoinjector delivers 150 mg omalizumab in 1 mL and contains arginine hydrochloride (42.1 mg), histidine (1.37 mg), L-histidine hydrochloride monohydrate (2.34 mg), and polysorbate 20 (0.4 mg) in SWFI, USP.
Each 300 mg prefilled syringe or autoinjector delivers 300 mg omalizumab in 2 mL and contains arginine hydrochloride (84.2 mg), histidine (2.74 mg), L-histidine hydrochloride monohydrate (4.68 mg), and polysorbate 20 (0.8 mg) in SWFI, USP.
The needle cap of the XOLAIR 75 mg/0.5 mL and 150 mg/mL prefilled syringe contains a derivative of natural rubber latex which may cause allergic reactions in latex sensitive individuals [see How Supplied/Storage and Handling (16)].
The XOLAIR autoinjector is not made with natural rubber latex
XOLAIR for Injection (Vial) XOLAIR (omalizumab) for injection is a sterile, white, preservative free, lyophilized powder in a single-dose vial. After reconstitution with 1.4 mL of Sterile Water for Injection, USP, the vial contains 150 mg of omalizumab per 1.2 mL of reconstituted solution for subcutaneous injection. Each 1.2 mL of reconstituted solution also contains histidine (1.3 mg), L-histidine hydrochloride monohydrate (2.1 mg), polysorbate 20 (0.4 mg) and sucrose (108 mg).
Sutton et al. is being used as an evidentiary reference to show that omalizumab (Xolair) is 98.7% monomer with .5% low molecular weight species as measured by SE-PLPLC. (In particular, Table V, whole document).
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666
1430
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491
1075
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Wang et al. is being used as an evidentiary reference for its teaching that omalizumab
charge variants when analyzed using CEX-HPLC show that the percentage of acid component was 8.2% ± .8%. (In particular, page 9, left column, whole document).
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696
729
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As such, the recitation of “wherein the pharmaceutical composition comprises the basic variants are about 10.80% or less determined by cation exchange high performance liquid chromatography” of claim 3 is inherent in the omalizumab product. While the omalizumab product insert reference is silent about these functional limitations, the omalizumab product is the same as the claimed pharmaceutical composition. Applicant is reminded that no more of the reference is required than that it sets forth the substance of the invention. The claimed functional limitations would be inherent properties of the referenced omalizumab composition. Products of identical chemical composition can not have mutually exclusive properties. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. In re Spada 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01.
The recitations of omalizumab purity of more than 96% of claims 1-3, more than 97% of claim 22, more than 98% of claims 23 and more than 99% of claims 1-7 and 12 are inherent in the omalizumab product.
The recitations of “wherein the pharmaceutical composition is prepared at 50L scale” of claims 25 and 27; and “wherein the pharmaceutical composition is prepared at 200L scale” of claims 3, 26 and 28 are included in this rejection because the patentability of a product does not depend on its method of production. In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985) See MPEP 2113.
Claims 2 and 8-12 are included in this rejection because since the office does not have a laboratory to test the reference antibodies using a different method, it is Applicant's burden to show that the reference antibody analyzed as taught in Sutton et al by SE-HPLC in Figure 4 does not comprise the particular low molecular weight variants LC, HC, HH and 2H1L in the amounts recited in the claim as determined by capillary electrophoresis sodium dodecyl sulfate (CE-SDS). See In re Best, 195 USPQ 430, 433 (CCPA 1977); In re Marosi, 218 USPQ 289, 292-293 (Fed. Cir. 1983); and In re Fitzgerald et al., 205 USPQ 594 (CCPA 1980).
The reference teachings anticipate the claimed invention.
20. 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.
21. Claims 1-28 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent Application Publication 2008/0167450 (IDS filed on 07/28/2025; Reference A15).
U.S. Patent Application Publication 2008/0167450 teaches purifying XOLAIR (omalizumab) using protein A and eluting with a pH gradient including as part of a manufacturing scale process to remove dimers and aggregates. (In particular, claims, whole document). The reference teaches that a variety of chromatographic methods can be performed subsequent to protein A and include size exclusion chromatography for native protein size, ion exchange, hydrophobic, reverse-phase based on solubility separation, dye binding and other chromatographic methods to characterize proteins (In particular, paragraph [0058] The reference specifically teaches that chromatography ceramic hydroxyapatite chromatography can be used to purify the reference antibodies to remove dimers and aggregates (In particular, paragraph [0061]; that anion exchange chromatography can be used for polishing (In particular, paragraph [0059]); and that viral inactivation can follow protein A chromatography for optimization. (In particular, paragraph [0057)
It would have been obvious to one of ordinary skill in the art at the time of invention to have used the purification techniques taught in U.S. Patent Application Publication 2008/0167450 to purify XOLAIR (omalizumab) as also taught in the reference. The process of purifying XOLAIR (Omalizumab) would have removed the impurities of the antibody composition leaving only the monomer with a complete lack of low molecular weight species and basic variants because the specification teaches on pages 14-15, 22, 24 and throughout the specification that these are the exact techniques that result in the pharmaceutical compositions as claimed which are enriched with omalizumab and substantially free of impurities HMW, LMW and basic variants. (In particular, specification at page 24, lines 18-20, whole document).
From the reference teachings, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the reference, especially in the absence of evidence to the contrary.
22. No claim is allowed.
23. Any inquiry concerning this communication or earlier communications from the examiner should be directed to NORA MAUREEN ROONEY whose telephone number is (571)272-9937. The examiner can normally be reached on M-F from 8:00am to 4:30pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner' s supervisor, Misook Yu, can be reached at telephone number (571) 272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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March 20, 2026
/Nora M Rooney/
Primary Examiner, Art Unit 1641
Prosecution Insights