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 .
Application Status
The Response to the Restriction Requirement filed on July 27, 2026 has been entered. Applicant’s election without traverse of the invention of Group I is acknowledged. Applicant submits that claims 1, 11, 31, 36, 42, 54, and 214-228 read on the elected invention.
The amended claims filed July 27, 2026 are acknowledged. Claims 1, 11, 31, 36, 42, 54, and 214-228 are pending. Claims 64, 98, 108, 114, 119, 128-129, 132, 139-140, 146, 168, 171, and 210 have been canceled. Claims 11, 31, 36, 42, and 54 are presently amended. No claims are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1, 11, 31, 36, 42, 54, and 214-228 are examined herein.
Specification
The disclosure is objected to because of the following informalities:
The numbering of the tables appearing throughout the specification is not presented in chronological order. For example, the first table to appear in the specification is labeled Table 6 (at page 37). Table 1 appears at page 221. The final table is Table 9B (at page 317), which appears after Table 60 (at page 315).
Applicant should correct the numbering of the tables in the disclosure such that the tables are numbered in order of their appearance. In addition, any in-text citations for each table should be corrected to reflect the updated table numbers.
Appropriate correction is required.
Claim Objections
Claims 42 and 217-218 are objected to because of the following informalities:
Claim 42 recites “or” in line 2 between “amino acid” and “polymer”, which is in addition to “or a combination thereof” at the end of the claim in lines 2-3. The extra “or” should be removed for clarity.
Appropriate correction is required.
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.
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.
(1) Claims 1, 11, 31, 36, 42, 54, 214-217, and 219-223 are rejected under 35 U.S.C. 103 as being unpatentable over McGovern (US 2018/0305459 A1; cited in IDS) in view of Kang (BioProcess International (2016) 14(4): 40-45), Parshad (US 2013/0028907 A1), and Arch (US 2015/0132311 A1; cited in IDS).
McGovern teaches methods of treating a subject with inflammatory bowel disease (IBD) (e.g., ) who is non-responsive to anti-TNF therapy with an inhibitor of TL1A, e.g., an anti-TL1A antibody (e.g., Abstract; ¶ 0012-0018, 0031-0037). In one embodiment of the invention, the anti-TL1A antibody comprises a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 150 (which shares 97.7% sequence identity to instant SEQ ID NO: 104 and comprises the HCDRs corresponding to instant SEQ ID NOs: 1, 2, and 6 or 7) and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 151 (which shares 99.3% sequence identity to instant SEQ ID NO: 203 and comprises the LCDRs corresponding to instant SEQ ID NOs: 10, 11, and 14), pertinent to claims 1 and 222-223. An antibody composition administered in a method of treatment would be recognized by those of ordinary skill in the art as being a pharmaceutical composition.
However, McGovern does not expressly teach that the pharmaceutical compositions of the invention comprise 10-50 mM (e.g., 20 mM) sodium acetate (NaOAc), 50-300 mM (e.g., 220 mM) sucrose, 10-100 mM (e.g., 40 mM) sodium chloride (NaCl), and 0.005-0.05% (e.g., 0.01%) polysorbate-20 (TWEEN™ 20), or a concentration of at least 95 mg/mL (e.g., 100, or 140, or 200 mg/mL).
Kang reviews formulation development for monoclonal antibodies (mAbs) and summarizes observations based on 37 commercial mAb formulations. Kang observed that acetate is among the most commonly used buffers, which keeps pH levels between 4.7 and 7.4 (e.g., page 40; Table 1), relevant to claims 1, 11, 54, 219-221, and 223. Kang teaches that sugars provide bulk and serve as a stabilizing agent in antibody formulations. Sucrose was found in 80% of lyophilized formulations and 30% of liquid formulations (e.g., page 40; Table 1). Kang further describes several stabilizers (e.g., sucrose and NaOAc) (e.g., page 40; Table 1), relevant to claims 1, 11, 42, 217, and 223. Kang teaches that 50% of formulations comprise NaCl, relevant to claims 1, 11, 36, 216, and 223. Polysorbate 80 and polysorbate 20 were noted among the most commonly used surfactants, pertinent to claims 1, 11, 31, 215, and 223. Kang teaches that in their platform approach, after selecting buffers to optimize for their desired pH, they will perform a screening study and choose one or two excipients from each of the categories of stabilizers (e.g., a sugar), surfactants, sodium chloride, amino acids, and antioxidants such as methionine (e.g., page 42). Following screening, during the in-depth evaluation of the most stabilizing buffer(s) and excipient(s), the mAb preparation is formulated at a target concentration and filled into the intended vial/stopper system (i.e., a container) to mimic a final-product configuration.
Parshad teaches, “high-concentration formulations of mAbs have been reported to result in increased viscosity thereby creating serious challenges for the manufacturability and injectability. … Papers have been published which show that NaCl may lower the viscosity and also to some extent control aggregation (EP 1981824). Sucrose has also shown to stabilise mAb against formation of aggregates by way of a preferential exclusion mechanism” (¶ 0004-0005). To address manufacturing and injectability challenges, Parshad formulated low-viscosity (<50 cP, e.g., between 1 and 10 cP), high-concentration antibody compositions that are suitable for subcutaneous administration and stable at room temperature, which have a protein concentration between 100 mg/mL and 300 mg/mL (e.g., Abstract; ¶ 0001, 0009-0015, 0043, 0054, 0215-0217), further relevant to claims 1 and 223. In embodiments of the invention, Parshad teaches that the total concentration of salt and buffer is 95 mM or lower. Parshad teaches the use of sodium chloride and sodium acetate as salts (e.g., at a concentration of 50 mM, or 40 mM, or 25 mM or lower) in the compositions of the invention (e.g., ¶ 0026-0031), further relevant to claims 1, 11, 36, 216, and 223. Parshad teaches the use of sucrose as a tonicity modifying agent, present in an amount between 50 mM and 250 mM (e.g., ¶ 0040-0041), further relevant to claims 1, 11, 42, 217, and 223. Parshad teaches the use of polysorbate-20 as a surfactant, at a concentration of 0.01% or below (e.g., ¶ 0036-0038), further relevant to claims 1, 11, 31, 215, and 223. Parshad further notes that the presence of additional ingredients including antioxidants should not adversely affect the overall stability of the pharmaceutical compositions of the invention (e.g., 0092).
Parshad additionally teaches that the final formulations were filled in cartridges at volumes between 0.5 mL to 5 mL (e.g., 3 mL or 0.6 mL as in Example 1; 1.5 mL as in Example 2), relevant to claim 214.
Arch further discloses pharmaceutical compositions comprising anti-TL1A antibodies, which have utility in the treatment of inflammatory bowel disease, ulcerative colitis, and other ailments (e.g., Abstract; claims 1, 10-12, and 16-20; ¶ 0604-0617). Arch discloses that antibodies of the invention may have a solubility of at least about 100 mg/mL, or at least about 150 mg/mL, or at least about 200 mg/mL, and a pH between 5.0 and 8.0 (e.g., ¶ 0011 at E60 and E62; ¶ 0859-0861), pertinent to claims 1 and 223. Arch further discloses that exemplary anti-TL1A antibody compositions of the invention comprise sodium acetate, a non-ionic surfactant such as 0.01% polysorbate-80 or polysorbate (TWEEN™) 20, isotonic agents such as sucrose and sodium chloride, and antioxidants such as methionine (e.g., ¶ 0859-0876; Examples 3, 8, 18; Table 38), further relevant to claims 1, 11, 31, 36, 42, 54, 215-217, 219-221, and 223. Arch teaches that surfactants maintain proper fluidity (e.g., ¶ 0869).
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described by McGovern, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) sodium acetate (NaOAc), 50-300 mM (e.g., 220 mM) sucrose, 10-100 mM (e.g., 40 mM) sodium chloride (NaCl), and 0.005-0.05% (e.g., 0.01%) polysorbate-20 (TWEEN™ 20), at a concentration of at least 95 mg/mL (e.g., 100 or 200 mg/mL), through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, as illustrated by Kang, there are a finite number of previously identified, predictably behaving options for buffers, surfactants, salts, and sugars available that one of ordinary skill in the art would reasonably expect to be successful based on their use in commercially available formulations. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and because Parshad and Arch provide a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein.
While McGovern, Kang, Parshad, and Arch do not expressly teach that the pharmaceutical compositions of the invention have a percentage aggregation of antibody that is less than about 5% of the total antibody in the composition (as set forth in claim 11), it is noted that products of identical composition cannot have mutually exclusive properties. A chemical composition and its properties are inseparable. In re Spada 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP § 2112.01.
(2) Claims 1, 11, 42, 218, and 223-224 are rejected under 35 U.S.C. 103 as being unpatentable over McGovern (US 2018/0305459 A1; supra) in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), and Arch (US 2015/0132311 A1; supra) as applied to claims 1, 11, 31, 36, 42, 54, 214-217, and 219-223 above, further in view of Bansal (WO 2016/109822 A1; cited in IDS) and Lacy (U.S. Patent No. 7,700,739; cited in IDS).
The teachings of McGovern, Kang, Parshad, and Arch are recited in the 35 U.S.C. § 103 rejection above.
However, McGovern does not expressly teach that the pharmaceutical compositions of the invention further comprise 50-300 mM or 25 mM L-methionine.
Bansal describes optimized aglycosylated therapeutic antibody formulations. Bansal teaches that methionine is an agent which can be included in a formulation of the invention to reduce viscosity and prevent antibody aggregation (e.g., page 2).
Lacy describes antibody formulations comprising against IL12/p40, which have utility in the treatment of ulcerative colitis, inflammatory bowel disease, and other ailments and are suitable for parenteral administration (e.g., col 3-14). Lacy teaches that 1-50 mM L-methionine can be incorporated into liquid and lyophilized dosage forms as a stabilizer (e.g., col 61).
Based on the further teachings of Bansal and Lacy, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to further modify the anti-TL1A antibody compositions described by McGovern such that L-methionine is present at a concentration within the range of 1-50 mM, e.g., 25 mM or 50 mM, determined through the process of routine optimization. The skilled artisan would have been motivated to do so because Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because Parshad teaches that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(3) Claims 1, 11, 31, 36, 42, 54, 214-217, 219-223, 225, and 227 are rejected under 35 U.S.C. 103 as being unpatentable over Watkins (US 2021/0122828 A1; filed December 2, 2020; cited in IDS) in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), and Arch (US 2015/0132311 A1; supra).
The applied reference of Watkins has a common Applicant (Prometheus Biosciences, Inc.) with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
Watkins discloses humanized anti-TL1A antibodies and pharmaceutical compositions comprising the same for treatment of IBD (e.g., Crohn’s disease or ulcerative colitis), which “possess features useful for therapeutic application such as low immunogenicity, and/or features that facilitate antibody manufacture, such as high percentage of monomeric fraction as measured by size-exclusion chromatography, and/or high expression” (¶ 0005) (e.g., Abstract; ¶ 0005, 0268-0286). In an exemplary embodiment, the anti-TL1A antibody comprises a VH having the amino acid sequence of SEQ ID NO: 104 (which shares 100% sequence identity to instant SEQ ID NO: 104 and comprises the HCDRs comprising instant SEQ ID NOs: 1, 2, and 7) and a VL having the amino acid sequence of SEQ ID NO: 201 (which shares 100% sequence identity with instant SEQ ID NO: 201 and comprises the LCDRs comprising instant SEQ ID NOs: 10, 11, and 12) (e.g., ¶ 0005-0008, 0277-0281), pertinent to claims 1, 223, 225, and 227.
Watkins further teaches antibodies comprising a VH comprising a HCDR1 comprising SEQ ID NO: 1, a HCDR2 comprising any one of SEQ ID NOs: 2-5, and a HCDR3 comprising any one of SEQ ID NOs: 6-9, and a VL comprising a LCDR1 comprising SEQ ID NO: 10, a LCDR2 comprising SEQ ID NO: 11, and a LCDR3 comprising any one of SEQ ID NO: 12-15 (e.g., ¶ 0010), which share 100% sequence identity to the respective HCDRs and LCDRs having the same sequence identifiers as instantly claimed (e.g., in claims 1 and 227).
Watkins teaches that the anti-TL1A antibodies of the invention “demonstrate advantageous viscosity and aggregation properties at high antibody concentrations (e.g. greater than 100 mg/mL or greater than 150 mg/mL). Notably, anti-TL1A antibodies provided herein are characterized by low viscosity (e.g. less than 10 mPa-s) and low aggregation (e.g. less than 5% high molecular weight species) at high concentrations (FIGS. 3A-3C)” (¶ 0276), relevant to claims 1, 11, 223, 225, and 227.
However, Watkins does not expressly teach that the pharmaceutical compositions of the invention comprise 10-50 mM (e.g., 20 mM) sodium acetate (NaOAc), 50-300 mM (e.g., 220 mM) sucrose, 10-100 mM (e.g., 40 mM) sodium chloride (NaCl), and 0.005-0.05% (e.g., 0.01%) polysorbate-20 (TWEEN™ 20).
The teachings of Kang, Parshad, and Arch are discussed in the 35 U.S.C. § 103 rejection above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described by Watkins, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) sodium acetate (NaOAc), 50-300 mM (e.g., 220 mM) sucrose, 10-100 mM (e.g., 40 mM) sodium chloride (NaCl), and 0.005-0.05% (e.g., 0.01%) polysorbate-20 (TWEEN™ 20), at a concentration of at least 95 mg/mL (e.g., 100 or 200 mg/mL), through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, as illustrated by Kang, there are a finite number of previously identified, predictably behaving options for buffers, surfactants, salts, and sugars available that one of ordinary skill in the art would reasonably expect to be successful based on their use in commercially available formulations. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and because Parshad and Arch provide a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein.
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
(4) Claims 1, 11, 42, 218, and 223-228 are rejected under 35 U.S.C. 103 as being unpatentable over Watkins (US 2021/0122828 A1; supra) in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), and Arch (US 2015/0132311 A1; supra) as applied to claims 1, 11, 31, 36, 42, 54, 214-217, 219-223, 225, and 227 above, further in view of Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The applied reference of Watkins has a common Applicant (Prometheus Biosciences, Inc.) with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
The teachings of Watkins, Kang, Parshad, and Arch are recited in the 35 U.S.C. § 103 rejections above.
Watkins does not expressly teach that the pharmaceutical compositions of the invention further comprise 50-300 mM or 25 mM L-methionine. However, this deficiency is remedied by Bansal and Lacy as set forth in the 35 U.S.C. § 103 rejection above.
Based on the further teachings of Bansal and Lacy, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to further modify the anti-TL1A antibody compositions described by Watkins such that L-methionine is present at a concentration within the range of 1-50 mM, e.g., 25 mM or 50 mM, determined through the process of routine optimization. The skilled artisan would have been motivated to do so because Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because Parshad teaches that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Double Patenting
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.
Non-Provisional Rejections
(1.1) Claims 1, 11, 31, 36, 42, 54, 214-221, and 223-226 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10,689,439 (cited in IDS) in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The reference patent claims a composition comprising an anti-TL1A antibody comprising heavy chain CDRs comprising SEQ ID NOs: 553, 554, and 565, respectively (which share 100% sequence identity to instant SEQ ID NOs: 1, 2, and 7, respectively) and light chain CDRs comprising the amino acid sequences of SEQ ID NOs: 569, 488, and 572, respectively (which share 100% sequence identity to instant SEQ ID NOs: 10-12, respectively) (e.g., patented claims 1-2, 4, 6, 12, and 18).
The reference patent does not disclose that the composition specifically comprises a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the reference patent, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(1.2) Claims 1, 222, and 227-228 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10,689,439 (cited in IDS) in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra) as applied to claims 1, 11, 31, 36, 42, 54, 214-221, and 223-226 above, further in view of Watkins (US 2021/0122828 A1; supra).
The teachings of the reference patent, Kang, Parshad, Bansal, and Lacy are recited in the non-statutory double patenting rejection above.
However, the reference patent does not disclose that the composition comprises a VH and VL comprising 100% sequence identity to instant SEQ ID NO: 104 and 201, respectively, or that the VH framework region comprises a human IGHV1-46*02 framework (or modified version thereof) and the VL framework region comprises a human IGKV3-20 framework (or modified version thereof), as set forth in the instant claims.
The teachings of Watkins are set forth in the 35 U.S.C. § 103 rejection above. In addition, Watkins sets forth that the humanized anti-TL1A antibodies of the invention comprise a VH framework region comprises a human IGHV1-46*02 framework or a modified version comprising less than 9 amino acid modifications thereof and the VL framework region comprises a human IGKV3-20 framework or a modified version comprising less than 9 amino acid modifications thereof (e.g., ¶ 0005-0006).
Based on the further teachings of Watkins, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the reference patent, wherein the antibody framework regions are modified such that the antibody comprises a VH having the amino acid sequence of SEQ ID NO: 104 and a VL having the amino acid sequence of SEQ ID NO: 201. The skilled artisan would have been motivated to do so because Watkins teaches that the antibodies of the invention have favorable therapeutic properties (e.g., low immunogenicity) and features that facilitate antibody manufacture (e.g., high expression and low percentage protein aggregation). There would have been a reasonable expectation of success because the antibodies claimed in the reference patent and by Watkins otherwise have identical heavy chain and light chain CDRs, and it was routine and conventional at the time of filing of the instantly claimed invention to optimize the framework regions of an antibody.
(2) Claims 223-224 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 10,332,174 (cited in IDS) in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The reference patent claims a composition comprising an anti-TL1A antibody or antigen-binding fragment thereof comprising three heavy chain CDRs and three light chain CDRs, and a pharmaceutically acceptable carrier.
The reference patent does not disclose that the composition specifically comprises a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the reference patent, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(3) Claims 223-224 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,292,848 (cited in IDS) in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The reference patent claims disclose an anti-TL1A antibody or antigen-binding fragment thereof comprising a heavy chain variable region (VH) having a human IGHV1-46*02 framework or a modified version thereof and a light chain variable region (VL) having a IGKV3-20 framework or a modified version thereof.
The reference patent does not expressly claim a pharmaceutical composition comprising said antibody, further comprising a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the reference patent, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(4.1) Claims 223-224 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-53 of U.S. Patent No. 11,136,386 (cited in IDS) in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The reference patent claims methods of treating moderately to severely active Crohn’s disease or ulcerative colitis by administering a generic anti-TL1A antibody or antigen-binding fragment thereof (e.g., patented claims 1-26).
The reference patent does not disclose that the pharmaceuticals compositions administered in said methods specifically comprise a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the reference patent, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(4.2) Claims 1, 11, 31, 36, 42, 54, and 214-222 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-53 of U.S. Patent No. 11,136,386 (cited in IDS) in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra) as applied to claims 223-224 above, further in view of McGovern (US 2018/0305459 A1; supra).
The teachings of the reference patent, Kang, Parshad, Bansal, and Lacy are recited in the non-statutory double patenting rejection above.
The reference patent does not claim that the anti-TL1A antibody comprises a combination of heavy chain and light chain CDRs such as set forth in claim 1. However, this deficiency is remedied by McGovern, the teachings of whom are set forth in the 35 U.S.C. § 103 rejection above.
Accordingly, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to substitute an anti-TL1A antibody such as that described by McGovern in the pharmaceutical composition administered in the treatment method of the patented claims. The skilled artisan would have been motivated to do so because McGovern teaches that the antagonist anti-TL1A antibodies of the invention similarly possess utility in the treatment of IBDs such as Crohn’s disease or ulcerative colitis. There would have been a reasonable expectation of success because the antibodies recited in the reference patent and by McGovern are functional equivalents known to be suitable for the same purpose.
(4.3) Claims 1, 11, 31, 36, 42, 54, 214-222, and 225-228 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-53 of U.S. Patent No. 11,136,386 (cited in IDS) in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra) as applied to claims 223-224 above, further in view of Watkins (US 2021/ 0122828 A1; supra).
The teachings of the reference patent, Kang, Parshad, Bansal, and Lacy are recited in the non-statutory double patenting rejection above.
The reference patent does not disclose that the composition comprises a VH and VL comprising 100% sequence identity to instant SEQ ID NO: 104 and 201, respectively, and the corresponding heavy chain and light chain CDRs thereof. However, this deficiency is remedied by Watkins, the teachings of whom are recited in the 35 U.S.C. § 103 and non-statutory double patenting rejections above.
Based on the further teachings of Watkins, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to substitute an anti-TL1A antibody such as that described by Watkins in the pharmaceutical composition administered in the treatment method of the patented claims. The skilled artisan would have been motivated to do so because Watkins teaches that the anti-TL1A antibodies of the invention have favorable therapeutic properties (e.g., low immunogenicity) and features that facilitate antibody manufacture (e.g., high expression and low percentage protein aggregation). There would have been a reasonable expectation of success because the antibodies recited in the reference patent and by Watkins are functional equivalents known to be suitable for the same purpose (i.e., treating IBDs such as Crohn’s disease or ulcerative colitis).
(5) Claims 1, 11, 31, 36, 42, 54, 214-224 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 12,540,358 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The reference patent claims a method of treating or preventing IBD that comprises administering an anti-TL1A antibody comprising a VH comprising SEQ ID NO: 356 (which shares 98.0% sequence identity to instant SEQ ID NO: 101 and comprises the HCDRs corresponding to instant SEQ ID NOs: 1, 2, and 7) and a VL comprising SEQ ID NO: 357 (which shares 99.3% sequence identity to instant SEQ ID NO: 203 and comprises the LCDRs corresponding to instant SEQ ID NOs: 10, 11, and 14). Alternatively, the anti-TL1A antibody or antigen-binding fragment thereof comprises VH CDRs of SEQ ID NOs: 346-348 (which share 100% sequence identity to instant SEQ ID NOs: 1, 2, and 6) and VL CDRs of SEQ ID NOs: 349-351 (which share 100% sequence identity to instant SEQ ID NOs: 10, 11, and 14) (e.g., patented claims 1-8).
The reference patent does not disclose that the pharmaceutical antibody compositions administered in the method specifically comprise a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the reference patent, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(6.1) Claims 223-224 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-45 of U.S. Patent No. 12,215,147 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The reference patent claims a method of treating IBD by administering a generic anti-TL1A antibody or antigen-binding fragment thereof (e.g., claims 1-23).
The reference patent does not disclose that the pharmaceutical antibody composition administered in the method specifically comprises a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the reference patent, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(6.2) Claims 1, 11, 31, 36, 42, 54, and 214-222 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-45 of U.S. Patent No. 12,215,147 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra) as applied to claims 223-224 above, further in view of McGovern (US 2018/0305459 A1; supra).
The teachings of the reference patent, Kang, Parshad, Bansal, and Lacy are recited in the non-statutory double patenting rejection above.
The reference patent does not claim that the anti-TL1A antibody comprises a combination of heavy chain and light chain CDRs such as set forth in claim 1. However, this deficiency is remedied by McGovern, the teachings of whom are set forth in the 35 U.S.C. § 103 rejection above.
Accordingly, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to substitute an anti-TL1A antibody such as that described by McGovern in the pharmaceutical composition administered in the treatment method of the patented claims. The skilled artisan would have been motivated to do so because McGovern teaches that the antagonist anti-TL1A antibodies of the invention similarly possess utility in the treatment of IBDs such as Crohn’s disease or ulcerative colitis. There would have been a reasonable expectation of success because the antibodies recited in the reference patent and by McGovern are functional equivalents known to be suitable for the same purpose.
(6.3) Claims 1, 11, 31, 36, 42, 54, 214-222, and 225-228 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-45 of U.S. Patent No. 12,215,147 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra) as applied to claims 223-224 above, further in view of Watkins (US 2021/ 0122828 A1; supra).
The teachings of the reference patent, Kang, Parshad, Bansal, and Lacy are recited in the non-statutory double patenting rejection above.
The reference patent does not disclose that the composition comprises a VH and VL comprising 100% sequence identity to instant SEQ ID NO: 104 and 201, respectively, and the corresponding heavy chain and light chain CDRs thereof. However, this deficiency is remedied by Watkins, the teachings of whom are recited in the 35 U.S.C. § 103 and non-statutory double patenting rejections above.
Based on the further teachings of Watkins, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to substitute an anti-TL1A antibody such as that described by Watkins in the pharmaceutical composition administered in the treatment method of the patented claims. The skilled artisan would have been motivated to do so because Watkins teaches that the anti-TL1A antibodies of the invention have favorable therapeutic properties (e.g., low immunogenicity) and features that facilitate antibody manufacture (e.g., high expression and low percentage protein aggregation). There would have been a reasonable expectation of success because the antibodies recited in the reference patent and by Watkins are functional equivalents known to be suitable for the same purpose (i.e., treating IBDs such as Crohn’s disease or ulcerative colitis).
(7) Claims 1, 11, 31, 36, 42, 54, and 214-228 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11,999,789 (cited in IDS) in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The reference patent claims an anti-TL1A antibody or antigen-binding fragment thereof that comprises a VH having the amino acid sequence of SEQ ID NO: 104 (which shares 100% sequence identity to instant SEQ ID NO: 104) and a VL comprising the amino acid sequence of SEQ ID NO: 201 (which shares 100% sequence identity to instant SEQ ID NO: 201).
The reference patent does not expressly disclose a pharmaceutical antibody composition that comprises a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the reference patent, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(8.1) Claims 223-224 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 10,633,449 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The reference patent claims methods of treating intestinal fibrosis or a TL1A-associated disease in a subject (e.g., Crohn’s disease, IBD), comprising the step of administering a therapeutically effective dosage of a generic blocking anti-TL1A antibody (e.g., patented claims 1, 10, 15, 17).
The reference patent does not disclose that the pharmaceutical antibody composition used to treat the subject comprises a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the reference patent, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(8.2) Claims 1, 11, 31, 36, 42, 54, and 214-222 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 10,633,449 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra) as applied to claims 223-224 above, further in view of McGovern (US 2018/0305459 A1; supra).
The teachings of the reference patent, Kang, Parshad, Bansal, and Lacy are recited in the non-statutory double patenting rejection above.
The reference patent does not claim that the anti-TL1A antibody comprises a combination of heavy chain and light chain CDRs such as set forth in claim 1. However, this deficiency is remedied by McGovern, the teachings of whom are set forth in the 35 U.S.C. § 103 rejection above.
Accordingly, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to substitute an anti-TL1A antibody such as that described by McGovern in the pharmaceutical composition administered in the treatment method of the patented claims. The skilled artisan would have been motivated to do so because McGovern teaches that the antagonist anti-TL1A antibodies of the invention similarly possess utility in the treatment of IBDs such as Crohn’s disease or ulcerative colitis. There would have been a reasonable expectation of success because the antibodies recited in the reference patent and by McGovern are functional equivalents known to be suitable for the same purpose.
(8.3) Claims 1, 11, 31, 36, 42, 54, 214-222, and 225-228 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 10,633,449 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra) as applied to claims 223-224 above, further in view of Watkins (US 2021/ 0122828 A1; supra).
The teachings of the reference patent, Kang, Parshad, Bansal, and Lacy are recited in the non-statutory double patenting rejection above.
The reference patent does not disclose that the composition comprises a VH and VL comprising 100% sequence identity to instant SEQ ID NO: 104 and 201, respectively, and the corresponding heavy chain and light chain CDRs thereof. However, this deficiency is remedied by Watkins, the teachings of whom are recited in the 35 U.S.C. § 103 and non-statutory double patenting rejections above.
Based on the further teachings of Watkins, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to substitute an anti-TL1A antibody such as that described by Watkins in the pharmaceutical composition administered in the treatment method of the patented claims. The skilled artisan would have been motivated to do so because Watkins teaches that the anti-TL1A antibodies of the invention have favorable therapeutic properties (e.g., low immunogenicity) and features that facilitate antibody manufacture (e.g., high expression and low percentage protein aggregation). There would have been a reasonable expectation of success because the antibodies recited in the reference patent and by Watkins are functional equivalents known to be suitable for the same purpose (i.e., treating IBDs such as Crohn’s disease or ulcerative colitis).
(9.1) Claims 223-224 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,434,296 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The reference patent claims methods of treating intestinal inflammation or fibrosis in a subject having an IBD such as Crohn’s disease, which comprises administering a therapeutically effective dosage of a generic anti-TL1A antibody (e.g., patented claims 1, 6, 11).
The reference patent does not disclose that the pharmaceutical antibody composition used to treat the subject comprises a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the reference patent, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(9.2) Claims 1, 11, 31, 36, 42, 54, and 214-222 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,434,296 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra) as applied to claims 223-224 above, further in view of McGovern (US 2018/0305459 A1; supra).
The teachings of the reference patent, Kang, Parshad, Bansal, and Lacy are recited in the non-statutory double patenting rejection above.
The reference patent does not claim that the anti-TL1A antibody comprises a combination of heavy chain and light chain CDRs such as set forth in claim 1. However, this deficiency is remedied by McGovern, the teachings of whom are set forth in the 35 U.S.C. § 103 rejection above.
Accordingly, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to substitute an anti-TL1A antibody such as that described by McGovern in the pharmaceutical composition administered in the treatment method of the patented claims. The skilled artisan would have been motivated to do so because McGovern teaches that the antagonist anti-TL1A antibodies of the invention similarly possess utility in the treatment of IBDs such as Crohn’s disease or ulcerative colitis. There would have been a reasonable expectation of success because the antibodies recited in the reference patent and by McGovern are functional equivalents known to be suitable for the same purpose.
(9.3) Claims 1, 11, 31, 36, 42, 54, 214-222, and 225-228 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,434,296 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra), as applied to claims 223-224 above, further in view of Watkins (US 2021/ 0122828 A1; supra).
The teachings of the reference patent, Kang, Parshad, Bansal, and Lacy are recited in the non-statutory double patenting rejection above.
The reference patent does not disclose that the composition comprises a VH and VL comprising 100% sequence identity to instant SEQ ID NO: 104 and 201, respectively, and the corresponding heavy chain and light chain CDRs thereof. However, this deficiency is remedied by Watkins, the teachings of whom are recited in the 35 U.S.C. § 103 and non-statutory double patenting rejections above.
Based on the further teachings of Watkins, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to substitute an anti-TL1A antibody such as that described by Watkins in the pharmaceutical composition administered in the treatment method of the patented claims. The skilled artisan would have been motivated to do so because Watkins teaches that the anti-TL1A antibodies of the invention have favorable therapeutic properties (e.g., low immunogenicity) and features that facilitate antibody manufacture (e.g., high expression and low percentage protein aggregation). There would have been a reasonable expectation of success because the antibodies recited in the reference patent and by Watkins are functional equivalents known to be suitable for the same purpose (i.e., treating IBDs such as Crohn’s disease or ulcerative colitis).
(10.1) Claims 223-224 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 12,590,160 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The reference patent claims a method of reversing intestinal fibrosis in a subject having IBD, which comprises administering a therapeutically effective dosage of a generic blocking anti-TL1A antibody (e.g., patented claims 1).
The reference patent does not disclose that the pharmaceutical antibody composition administered to the subject comprises a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the reference patent, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(10.2) Claims 1, 11, 31, 36, 42, 54, and 214-222 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 12,590,160 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra), further in view of McGovern (US 2018/0305459 A1; supra).
The teachings of the reference patent, Kang, Parshad, Bansal, and Lacy are recited in the non-statutory double patenting rejection above.
The reference patent does not claim that the anti-TL1A antibody comprises a combination of heavy chain and light chain CDRs such as set forth in claim 1. However, this deficiency is remedied by McGovern, the teachings of whom are set forth in the 35 U.S.C. § 103 rejection above.
Accordingly, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to substitute an anti-TL1A antibody such as that described by McGovern in the pharmaceutical composition administered in the treatment method of the patented claims. The skilled artisan would have been motivated to do so because McGovern teaches that the antagonist anti-TL1A antibodies of the invention similarly possess utility in the treatment of IBDs such as Crohn’s disease or ulcerative colitis. There would have been a reasonable expectation of success because the antibodies recited in the reference patent and by McGovern are functional equivalents known to be suitable for the same purpose.
(10.3) Claims 1, 11, 31, 36, 42, 54, 214-222, and 225-228 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 12,590,160 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra) further in view of Watkins (US 2021/ 0122828 A1; supra).
The teachings of the reference patent, Kang, Parshad, Bansal, and Lacy are recited in the non-statutory double patenting rejection above.
The reference patent does not disclose that the composition comprises a VH and VL comprising 100% sequence identity to instant SEQ ID NO: 104 and 201, respectively, and the corresponding heavy chain and light chain CDRs thereof. However, this deficiency is remedied by Watkins, the teachings of whom are recited in the 35 U.S.C. § 103 and non-statutory double patenting rejections above.
Based on the further teachings of Watkins, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to substitute an anti-TL1A antibody such as that described by Watkins in the pharmaceutical composition administered in the treatment method of the patented claims. The skilled artisan would have been motivated to do so because Watkins teaches that the anti-TL1A antibodies of the invention have favorable therapeutic properties (e.g., low immunogenicity) and features that facilitate antibody manufacture (e.g., high expression and low percentage protein aggregation). There would have been a reasonable expectation of success because the antibodies recited in the reference patent and by Watkins are functional equivalents known to be suitable for the same purpose (i.e., treating IBDs such as Crohn’s disease or ulcerative colitis).
Provisional Rejections
(1) Claims 223-224 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21-23, 26-32, 36-38, 43, and 50-51 of co-pending Application No. 15/931,452 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The co-pending reference application claims a method of treating an inflammatory bowel disease by administering an anti-TL1A antibody comprising three heavy chain CDRs and three light chain CDRs (e.g., co-pending claim 21, 26-32).
The co-pending reference application does not claim that the composition specifically comprises a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the co-pending claims, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(2) Claims 1, 11, 31, 36, 42, 54, and 214-224 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-6, 28-38, and 40 of co-pending Application No. 17/050,067 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The co-pending reference application claims a method of treating Crohn’s disease by administering an anti-TL1A antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 356 (which shares 100% sequence identity to instant SEQ ID NO: 104 and comprises the HCDRs of instant SEQ ID NOs: 1, 2, and 7) and a VL comprising the amino acid sequence of SEQ ID NO: 357 (which shares 99.3% sequence identity to instant SEQ ID NO: 203 and comprises the LCDRs of instant SEQ ID NOs: 10, 11, and 14) (e.g., co-pending claim 1).
The co-pending reference application does not claim that the composition specifically comprises a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the co-pending claims, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(3.1) Claims 223-224 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 12, 14, 17, 19, 28, 31, and 33-38 of co-pending Application No. 17/334,109 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The co-pending reference application claims methods of treating Crohn’s disease by administering a generic anti-TL1A antibody.
The co-pending reference application does not claim that the pharmaceutical antibody composition specifically comprises a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the co-pending claims, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(3.2) Claims 1, 11, 31, 36, 42, 54, and 214-222 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 12, 14, 17, 19, 28, 31, and 33-38 of co-pending Application No. 17/334,109 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra) as applied to claims 223-224 above, further in view of McGovern (US 2018/0305459 A1; supra).
The teachings of the co-pending reference application, Kang, Parshad, Bansal, and Lacy are recited in the non-statutory double patenting rejection above.
The co-pending reference application does not claim that the anti-TL1A antibody comprises a combination of heavy chain and light chain CDRs such as set forth in claim 1. However, this deficiency is remedied by McGovern, the teachings of whom are set forth in the 35 U.S.C. § 103 rejection above.
Accordingly, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to substitute an anti-TL1A antibody such as that described by McGovern in the pharmaceutical composition administered in the treatment method of the co-pending claims. The skilled artisan would have been motivated to do so because McGovern teaches that the antagonist anti-TL1A antibodies of the invention similarly possess utility in the treatment of IBDs such as Crohn’s disease or ulcerative colitis. There would have been a reasonable expectation of success because the antibodies recited in the reference patent and by McGovern are functional equivalents known to be suitable for the same purpose.
(3.3) Claims 1, 11, 31, 36, 42, 54, 214-222, and 225-228 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 12, 14, 17, 19, 28, 31, and 33-38 of co-pending Application No. 17/334,109 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra) as applied to claims 223-224 above, further in view of Watkins (US 2021/ 0122828 A1; supra).
The teachings of the co-pending reference application, Kang, Parshad, Bansal, and Lacy are recited in the non-statutory double patenting rejection above.
The co-pending claims do not disclose that the composition comprises a VH and VL comprising 100% sequence identity to instant SEQ ID NO: 104 and 201, respectively, and the corresponding heavy chain and light chain CDRs thereof. However, this deficiency is remedied by Watkins, the teachings of whom are recited in the 35 U.S.C. § 103 and non-statutory double patenting rejections above.
Based on the further teachings of Watkins, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to substitute an anti-TL1A antibody such as that described by Watkins in the pharmaceutical composition administered in the treatment method of the co-pending claims. The skilled artisan would have been motivated to do so because Watkins teaches that the anti-TL1A antibodies of the invention have favorable therapeutic properties (e.g., low immunogenicity) and features that facilitate antibody manufacture (e.g., high expression and low percentage protein aggregation). There would have been a reasonable expectation of success because the antibodies recited in the reference patent and by Watkins are functional equivalents known to be suitable for the same purpose (i.e., treating IBDs such as Crohn’s disease or ulcerative colitis).
(4.1) Claims 223-224 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 5-11, 13-14, 42, and 48-53 of co-pending Application No. 18/008,146 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The co-pending reference application claims methods that comprise administering a therapeutically effective amount of a generic anti-TL1A antibody to a subject having Crohn’s disease (e.g., co-pending claims 1 and 42).
The co-pending reference application does not claim that the pharmaceutical antibody composition specifically comprises a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the co-pending claims, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(4.2) Claims 1, 11, 31, 36, 42, 54, and 214-222 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 5-11, 13-14, 42, and 48-53 of co-pending Application No. 18/008,146 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra) as applied to claims 223-224 above, further in view of McGovern (US 2018/0305459 A1; supra).
The teachings of the co-pending reference application, Kang, Parshad, Bansal, and Lacy are recited in the non-statutory double patenting rejection above.
The co-pending reference application does not claim that the anti-TL1A antibody comprises a combination of heavy chain and light chain CDRs such as set forth in claim 1. However, this deficiency is remedied by McGovern, the teachings of whom are set forth in the 35 U.S.C. § 103 rejection above.
Accordingly, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to substitute an anti-TL1A antibody such as that described by McGovern in the pharmaceutical composition administered in the treatment method of the co-pending claims. The skilled artisan would have been motivated to do so because McGovern teaches that the antagonist anti-TL1A antibodies of the invention similarly possess utility in the treatment of IBDs such as Crohn’s disease or ulcerative colitis. There would have been a reasonable expectation of success because the antibodies recited in the reference patent and by McGovern are functional equivalents known to be suitable for the same purpose.
(4.3) Claims 1, 11, 31, 36, 42, 54, 214-222, and 225-228 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 5-11, 13-14, 42, and 48-53 of co-pending Application No. 18/008,146 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra) as applied to claims 223-224 above, further in view of Watkins (US 2021/ 0122828 A1; supra).
The teachings of the co-pending reference application, Kang, Parshad, Bansal, and Lacy are recited in the non-statutory double patenting rejection above.
The co-pending claims do not disclose that the composition comprises a VH and VL comprising 100% sequence identity to instant SEQ ID NO: 104 and 201, respectively, and the corresponding heavy chain and light chain CDRs thereof. However, this deficiency is remedied by Watkins, the teachings of whom are recited in the 35 U.S.C. § 103 and non-statutory double patenting rejections above.
Based on the further teachings of Watkins, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to substitute an anti-TL1A antibody such as that described by Watkins in the pharmaceutical composition administered in the treatment method of the co-pending claims. The skilled artisan would have been motivated to do so because Watkins teaches that the anti-TL1A antibodies of the invention have favorable therapeutic properties (e.g., low immunogenicity) and features that facilitate antibody manufacture (e.g., high expression and low percentage protein aggregation). There would have been a reasonable expectation of success because the antibodies recited in the reference patent and by Watkins are functional equivalents known to be suitable for the same purpose (i.e., treating IBDs such as Crohn’s disease or ulcerative colitis).
(5) Claims 223-224 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15, 17-20, and 58 of co-pending Application No. 18/008,150 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The co-pending reference application claims a method of treating or preventing a disease or condition of gastrointestinal tissue in a subject, comprising the step of administering anti-TL1A antibody A100 (e.g., claims 1, 4, 6-9, 19-20).
The co-pending reference application does not claim that the pharmaceutical antibody composition administered in the method specifically comprises a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the co-pending claims, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(6) Claims 1, 11, 31, 36, 42, 54, and 214-228 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 7, 9, 12-13, 15-16, 18-20, 22, 26-28, 47, 80, 85, and 90 of co-pending Application No. 18/316,811 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The co-pending reference application claims a method of treating Crohn’s disease or ulcerative colitis in a subject, which comprises administering an anti-TL1A antibody comprising a VH having the amino acid sequence of SEQ ID NO: 104 (which shares 100% sequence identity to instant SEQ ID NO: 104) and a VL having the amino acid sequence of SEQ ID NO: 201 (which shares 100% sequence identity to instant SEQ ID NO: 201).
The co-pending reference application does not claim that the pharmaceutical antibody composition administered in the method specifically comprises a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the co-pending claims, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(7.1) Claims 223-224 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 9, 12-15, 51-59 of co-pending Application No. 18/326,912 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The co-pending reference application claims methods of treating Crohn’s disease by administering a generic anti-TL1A antibody (e.g., claims 1, 15).
The co-pending reference application does not claim that the pharmaceutical antibody composition administered in the method specifically comprises a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the co-pending claims, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(7.2) Claims 1, 11, 31, 36, 42, 54, and 214-222 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 9, 12-15, 51-59 of co-pending Application No. 18/326,912 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra) as applied to claims 223-224 above, further in view of McGovern (US 2018/0305459 A1; supra).
The teachings of the co-pending reference application, Kang, Parshad, Bansal, and Lacy are recited in the non-statutory double patenting rejection above.
The co-pending reference application does not claim that the anti-TL1A antibody comprises a combination of heavy chain and light chain CDRs such as set forth in claim 1. However, this deficiency is remedied by McGovern, the teachings of whom are set forth in the 35 U.S.C. § 103 rejection above.
Accordingly, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to substitute an anti-TL1A antibody such as that described by McGovern in the pharmaceutical composition administered in the treatment method of the co-pending claims. The skilled artisan would have been motivated to do so because McGovern teaches that the antagonist anti-TL1A antibodies of the invention similarly possess utility in the treatment of IBDs such as Crohn’s disease or ulcerative colitis. There would have been a reasonable expectation of success because the antibodies recited in the reference patent and by McGovern are functional equivalents known to be suitable for the same purpose.
(7.3) Claims 1, 11, 31, 36, 42, 54, 214-222, and 225-228 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 9, 12-15, 51-59 of co-pending Application No. 18/326,912 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra) as applied to claims 223-224 above, further in view of Watkins (US 2021/0122828 A1; supra).
The teachings of the co-pending reference application, Kang, Parshad, Bansal, and Lacy are recited in the non-statutory double patenting rejection above.
The co-pending claims do not disclose that the composition comprises a VH and VL comprising 100% sequence identity to instant SEQ ID NO: 104 and 201, respectively, and the corresponding heavy chain and light chain CDRs thereof. However, this deficiency is remedied by Watkins, the teachings of whom are recited in the 35 U.S.C. § 103 and non-statutory double patenting rejections above.
Based on the further teachings of Watkins, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to substitute an anti-TL1A antibody such as that described by Watkins in the pharmaceutical composition administered in the treatment method of the co-pending claims. The skilled artisan would have been motivated to do so because Watkins teaches that the anti-TL1A antibodies of the invention have favorable therapeutic properties (e.g., low immunogenicity) and features that facilitate antibody manufacture (e.g., high expression and low percentage protein aggregation). There would have been a reasonable expectation of success because the antibodies recited in the reference patent and by Watkins are functional equivalents known to be suitable for the same purpose (i.e., treating IBDs such as Crohn’s disease or ulcerative colitis).
(8) Claims 1, 11, 31, 36, 42, 54, and 214-228 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 204-217 of co-pending Application No. 18/546,947. Although the claims at issue are not identical, they are not patentably distinct from each other because the treatment method recited in the co-pending claims necessarily requires possession of the pharmaceutical composition used in said method.
The co-pending reference application claims a method of treating systemic sclerosis-associated interstitial lung disease in a subject, comprising administering an anti-TL1A antibody comprising a VH comprising SEQ ID NO: 104 (which shares 100% sequence identity with instant SEQ ID NO: 104) and a VL comprising the amino acid sequence of SEQ ID NO: 201 (which shares 100% sequence identity with instant SEQ ID NO: 201). Co-pending claim 205 recites that the pharmaceutical antibody composition administered in the method comprises the antibody at a concentration of about 150 mg/L to about 250 mg/mL, relevant to claims 1, 222-223, 225, and 227. Co-pending claim 206 recites that the composition has a total volume of about 0.5 mL to about 1.5 mL; a viscosity of less than about 20 cP; or a percentage aggregation of anti-TL1A antibody of less than about 2% as measured by size exclusion chromatography, pertinent to claims 1, 11, and 214.
Regarding claims 1, 31, 36, 42, 54, and 215-221, co-pending claims 207-208 recite that the pharmaceutical composition comprises a non-ionic surfactant, e.g., polysorbate-20, at a concentration of about 0.005% to 0.05%; a salt, e.g., NaCl, at a concentration of 10-100 mM; a stabilizer at a concentration of about 50 mM to about 300 mM, e.g., sucrose or L-methionine; and a buffering agent, e.g., acetate, at a concentration of about 10 mM to about 50 mM; and that the pH is 5.3. Regarding claims 223-228, co-pending claims 207-208 further recites that the pharmaceutical composition comprises 20 mM sodium acetate, 220 mM sucrose, 40 mM NaCl, 0.01% (v/v) polysorbate-20, and 25 mM L-methionine, at pH 5.3.
(9.1) Claims 1, 11, 31, 36, 42, 54, 214-221, and 223-224 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 52 and 70-87 of co-pending Application No. 18/557,551 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The co-pending reference application claims methods that comprise administering an anti-TL1A antibody comprising VH CDRs of SEQ ID NOs: 1, 2, and 6 (which share 100% sequence identity to instant SEQ ID NOs: 1, 2, and 6) and VL CDRs of SEQ ID NOs: 10-12 (which share 100% sequence identity to instant SEQ ID NO: 10-12) to a subject with an inflammatory disease (e.g., Crohn’s disease or ulcerative colitis).
The co-pending reference application does not claim that the pharmaceutical composition antibody compositions administered in the methods specifically comprise a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the co-pending claims, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(9.2) Claims 1 and 222 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 52 and 70-87 of co-pending Application No. 18/557,551 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra) as applied to claims 1, 11, 31, 36, 42, 54, 214-221, and 223-224 above, further in view of Watkins (US 2021/0122828 A1; supra).
The teachings of the co-pending reference application, Kang, Parshad, Bansal, and Lacy are recited in the non-statutory double patenting rejection above.
The co-pending reference application does not disclose that the composition comprises the VH framework region of the anti-TL1A antibody comprises a human IGHV1-46*02 framework (or modified version thereof) and that the VL framework region of said antibody comprises a human IGKV3-20 framework (or modified version thereof), as set forth in the instant claims.
The teachings of Watkins are set forth in the 35 U.S.C. § 103 and non-statutory double patenting rejections above.
Based on the further teachings of Watkins, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the co-pending reference application, wherein the antibody framework regions are modified such that the antibody comprises a VH framework region of the anti-TL1A antibody comprises a human IGHV1-46*02 framework (or modified version thereof) and a VL framework region of said antibody comprises a human IGKV3-20 framework (or modified version thereof). The skilled artisan would have been motivated to do so because Watkins teaches that the antibodies of the invention have favorable therapeutic properties (e.g., low immunogenicity) and features that facilitate antibody manufacture (e.g., high expression and low percentage protein aggregation). There would have been a reasonable expectation of success because the antibodies claimed in the co-pending reference application and by Watkins otherwise have identical heavy chain and light chain CDRs, and it was routine and conventional at the time of filing of the instantly claimed invention to optimize the framework regions of an antibody.
(10) Claims 1, 11, 31, 36, 42, 54, and 214-228 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of co-pending Application No. 18/645,261 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The co-pending reference application claims methods of treating an IBD (e.g., Crohn’s disease or ulcerative colitis) in which a subject is administered an anti-TL1A antibody comprising a VH comprising the amino acid sequence of SEQ ID NO: 104 (which shares 100% sequence identity to instant SEQ ID NO: 104) and a VL comprising the amino acid sequence of SEQ ID NO: 201 (which shares 100% sequence identity to instant SEQ ID NO: 201.
The co-pending reference application does not claim that the pharmaceutical antibody composition administered in the method specifically comprises a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the co-pending claims, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(11) Claims 1, 11, 31, 36, 42, 54, and 214-228 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4, 6-8, 12, 16, 21, 28, 30-31, 36, 42, 46, and 64-65 of co-pending Application No. 18/724,826 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The co-pending reference application claims pharmaceutical composition comprising an anti-TL1A antibody comprising an identical combination of heavy chain and light chain CDRs as set forth in instant claims 1 and 225, and comprising the same framework and/or VH/VL sequences/structures as set forth in instant claims 222 and 227, as well as a method of treating an inflammatory disease by administering the same (e.g., co-pending claims 1, 6, 12, 16, 28, 30-31, 36, 42, 64).
The co-pending reference application does not claim that the pharmaceutical composition specifically comprises a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody pharmaceutical composition such as that described in the co-pending claims, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(12) Claims 1, 11, 31, 36, 42, 54, and 214-228 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-4, 6, 10, 21, 40, 42, 83, 102-103, 112, 115, 132, 135, 142 of co-pending Application No. 19/129,758 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The co-pending reference application claims methods of treating an inflammatory disorder that comprise administering an anti-TL1A antibody comprising an identical combination of heavy chain and light chain CDR sequences as set forth in instant claim 1 and/or comprise a VH having the amino acid sequence of SEQ ID NO: 104 (which shares 100% sequence identity to instant SEQ ID NO: 104) and a VL comprising the amino acid sequence of SEQ ID NO: 201 (which share 100% sequence identity to instant SEQ ID NO: 201) (e.g., co-pending claims 1, 102-103, 112, 115).
The co-pending reference application does not claim that the pharmaceutical antibody composition administered in the method specifically comprises a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the co-pending claims, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(13) Claims 1, 11, 31, 36, 42, 54, and 214-228 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4, 6-8, 12, 16, 21, 28, 30-31, 36, 41-42, 46, 67-68 of co-pending Application No. 19/137,697 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The co-pending reference application claims a pharmaceutical composition comprising an anti-TL1A antibody comprising an identical combination of heavy chain and light chain CDRs as set forth in instant claims 1 and 225, and comprising the same framework and/or VH/VL sequences/structures as set forth in instant claims 222 and 227, as well as a method of treating an inflammatory disease by administering the same (e.g., co-pending claims 1, 12, 16, 30-31, 36, 42, 67).
The co-pending reference application does not claim that the pharmaceutical composition specifically comprises a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the co-pending claims, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(14) Claims 1, 11, 31, 36, 42, 54, and 214-228 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4, 6-8, 12, 16, 21, 28, 30-31, 36, 41-42, 46, 60-61 of co-pending Application No. 19/145,064 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The co-pending reference application claims a pharmaceutical composition comprising an anti-TL1A antibody comprising an identical combination of heavy chain and light chain CDRs as set forth in instant claims 1 and 225, and comprising the same framework and/or VH/VL sequences/structures as set forth in instant claims 222 and 227, as well as a method of treating an inflammatory disease by administering the same (e.g., co-pending claims 1, 12, 16, 28, 30-31, 36, 42, 60).
The co-pending reference application does not claim that the pharmaceutical composition specifically comprises a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the co-pending claims, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(15) Claims 1, 11, 31, 36, 42, 54, and 214-228 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4, 6-8, 12, 16, 21, 28, 30-31, 36, 41-42, 46, 55, 58-59 of co-pending Application No. 19/145,066 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The co-pending reference application claims a pharmaceutical composition comprising an anti-TL1A antibody comprising an identical combination of heavy chain and light chain CDRs as set forth in instant claims 1 and 225, and comprising the same framework and/or VH/VL sequences/structures as set forth in instant claims 222 and 227, as well as a method of treating an inflammatory disease by administering the same (e.g., co-pending claims 1, 12, 16, 28, 30-31, 36, 42, 58).
The co-pending reference application does not claim that the pharmaceutical composition specifically comprises a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the co-pending claims, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(16.1) Claims 1, 11, 31, 36, 42, 54, 214-217, 219-223, 225, and 227 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-199 of co-pending Application No. 19/157,152.
The co-pending reference application claims methods of treatment comprising the step of administering a pharmaceutical composition comprising an anti-TL1A antibody (e.g., co-pending claims 1-11). Co-pending claims 12-15 recite that the concentration of antibody is greater than 150 mg/mL or is about 150 mg/ml to about 250 mg/mL, pertinent to claims 1, 223, 225, and 227. Co-pending claims 18-21 recite that the total volume is less than or equal to 2.0 mL, relevant to claim 214. Co-pending claims 22-24 recite that the viscosity is less than 20 cP, further relevant to claim 1. Co-pending claims 25-26 recites that the percentage antibody aggregation in the pharmaceutical composition is less than about 5%, relevant to claim 11.
Co-pending claims 27-31 recite that the composition comprises about 0.01% to about 0.02% polysorbate-20, relevant to claims 1, 11, 31, 215, 223, 225, and 227. Co-pending claims 32-38 recite that the pharmaceutical composition comprises about 10 mM to about 100 mM NaCl, or about 40 mM NaCl, pertinent to claims 1, 11, 36, 216, 223, 225, and 227. Co-pending claims 39-46 recite that the pharmaceutical composition comprises sucrose as a stabilizer, at a concentration of about 50-300 mM or about 200-280 mM or 220-240 mM, relevant to claims 1, 11, 42, 217, 223, 225, and 227. Co-pending claims 47-51 recite that the pharmaceutical composition comprises acetate buffer at a concentration of about 10-50 mM or about 20 mM, relevant to claims 1, 11, 54, 219, 223, 225, and 227. Co-pending claims 52-55 recite that the pharmaceutical composition has a pH of about 4.5-7.5, or about 5.3, relevant to claims 1, 220-221, 223, 225, and 227. Co-pending claims 196-199 recite that the anti-TL1A antibody comprises an identical combination of heavy chain and light chain CDRs as set forth in claims 1 and 225, and/or a VH comprising the amino acid sequence of SEQ ID NO: 104 (which shares 100% sequence identity to instant SEQ ID NO: 104) and a VL comprising the amino acid sequence of SEQ ID NO: 201 (which shares 100% sequence identity to instant SEQ ID NO: 201) as set forth in claims 222, 225, and 227.
(16.2) Claims 1, 11, 42, 218, and 223-228 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-199 of co-pending Application No. 19/157,152 as applied to claims 1, 11, 31, 36, 42, 54, 214-217, 219-223, 225, and 227 above, further in view of Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The teachings of the co-pending reference application are recited in the provisional NSDP rejection (16.1) above.
The co-pending reference application does not claim that the pharmaceutical composition specifically comprises L-methionine, formulated as set forth in the instant claims. However, this deficiency is remedied by Bansal and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Based on the further teachings of Bansal and Lacy, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to modify the anti-TL1A antibody formulation described in the co-pending claims, such that the formulation further comprises 1-50 mM, e.g., 25 mM or 50 mM L-methionine, as determined through the process of routine optimization. The skilled artisan would have been motivated to do so because Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success as Lacy provides a proof-of-concept that L-methionine can be successfully incorporated into antibody-containing pharmaceutical compositions.
(17.1) Claims 1, 11, 31, 36, 42, 54, 215-223, 225, and 227 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 13, 20, 25-26, 39, 42, 47, 54, 62, 66, 70, 74, 113-114, 118, 125, 128, 131, 138-139, 145, 178, 181, 221, and 225-227 of co-pending Application No. 19/157,176.
The co-pending reference application claims methods of treatment wherein an anti-TL1A antibody pharmaceutical composition is administered to a subject in need thereof, wherein the anti-TL1A antibody comprises an identical combination of heavy chain and light chain CDRs as set forth in instant claims 1 and 225, and comprises the same framework and/or VH/VL sequences/structures as set forth in instant claims 222 and 227 (e.g., co-pending claims 1, 25-26, 113, 118, 221, 225-226). Co-pending claims 25-26 and 39 recite that the percentage antibody aggregation in the composition is less than 5%, pertinent to claim 11. Co-pending claims 25-26, 42, 47, 54, and 62 further recite that the pharmaceutical composition has a viscosity of less than about 20 cP and a concentration greater than about 95 mg/mL, and further comprises 0.005% to 0.05% surfactant (polysorbate-20), 10-100 mM salt (NaCl), 50-300 mM stabilizer (sucrose or L-methionine), and 10-50 mM of buffering agent (acetate), pertinent to claims 1, 11, 31, 36, 42, 54, and 215-219. Co-pending claim 66 recites that the composition has a pH of about 5.3, pertinent to claims 1, 220-221, 223, 225, and 227.
(17.2) Claims 1, 214, and 223-228 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 13, 20, 25-26, 39, 42, 47, 54, 62, 66, 70, 74, 113-114, 118, 125, 128, 131, 138-139, 145, 178, 181, 221, and 225-227 of co-pending Application No. 19/157,176 as applied to claims 1, 11, 31, 36, 42, 54, 215-223, 225, and 227 above, further in view of Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The teachings of the co-pending reference application are recited in the provisional NSDP rejection (17.1) above.
The co-pending reference application does not claim that the composition has a total volume between 0.5-5 mL or that the formulation comprises about 25 mM L-methionine. However, these deficiencies are remedied by Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Based on the further teachings of Parshad, Bansal, and Lacy, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to modify the anti-TL1A antibody formulation described in the co-pending claims, such that the formulation further comprises 25 mM L-methionine, as determined through the process of routine optimization. The skilled artisan would have been motivated to do so because Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. Furthermore, formulating the total volume at 0.5-5 mL would enable one to readily administer the pharmaceutical composition in a method of treatment. There would have been a reasonable expectation of success as Parshad teaches that the addition of an antioxidant such as L-methionine does not impact the stability of the composition, and Lacy provides a proof-of-concept that L-methionine can be successfully incorporated into antibody-containing pharmaceutical compositions.
(18.1) Claims 1, 11, 31, 36, 42, 54, 214-217, 219-223, 225, and 227 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-201 of co-pending Application No. 19/157,273.
The co-pending reference application claims methods of treatment comprising the step of administering a pharmaceutical composition comprising an anti-TL1A antibody (e.g., co-pending claims 1-12). Co-pending claims 13-17 recite that the antibody is administered as a pharmaceutical composition with a concentration of antibody that is greater than 150 mg/mL or is about 150 mg/ml to about 250 mg/mL, pertinent to claims 1, 223, 225, and 227. Co-pending claims 20-23 recite that the total volume is less than or equal to 2.0 mL, relevant to claim 214. Co-pending claims 24-26 recite that the viscosity is less than 20 cP, further relevant to claim 1. Co-pending claims 27-28 recites that the percentage antibody aggregation in the pharmaceutical composition is less than about 5%, relevant to claim 11.
Co-pending claims 29-33 recite that the composition comprises about 0.01% to about 0.02% polysorbate-20, relevant to claims 1, 11, 31, 215, 223, 225, and 227. Co-pending claims 34-40 recite that the pharmaceutical composition comprises about 10 mM to about 100 mM NaCl, or about 40 mM NaCl, pertinent to claims 1, 11, 36, 216, 223, 225, and 227. Co-pending claims 41-48 recite that the pharmaceutical composition comprises sucrose as a stabilizer, at a concentration of about 50-300 mM or about 200-280 mM or 220-240 mM, relevant to claims 1, 11, 42, 217, 223, 225, and 227. Co-pending claims 49-53 recite that the pharmaceutical composition comprises acetate buffer at a concentration of about 10-50 mM or about 20 mM, relevant to claims 1, 11, 54, 219, 223, 225, and 227. Co-pending claims 54-57 recite that the pharmaceutical composition has a pH of about 4.5-7.5, or about 5.3, relevant to claims 1, 220-221, 223, 225, and 227.
Co-pending claims 198-201 recite that the anti-TL1A antibody comprises an identical combination of heavy chain and light chain CDRs as set forth in claims 1 and 225, and/or a VH comprising the amino acid sequence of SEQ ID NO: 104 (which shares 100% sequence identity to instant SEQ ID NO: 104) and a VL comprising the amino acid sequence of SEQ ID NO: 201 (which shares 100% sequence identity to instant SEQ ID NO: 201) as set forth in claims 222, 225, and 227.
(18.2) Claims 1, 11, 42, 218, and 223-228 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-201 of co-pending Application No. 19/157,273 as applied to claims 1, 11, 31, 36, 42, 54, 214-217, 219-223, 225, and 227 above, further in view of Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The teachings of the co-pending reference application are recited in the provisional NSDP rejection (18.1) above.
The co-pending reference application does not claim that the pharmaceutical composition specifically comprises L-methionine, formulated as set forth in the instant claims. However, this deficiency is remedied by Bansal and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Based on the further teachings of Bansal and Lacy, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to modify the anti-TL1A antibody formulation described in the co-pending claims, such that the formulation further comprises 1-50 mM, e.g., 25 mM, L-methionine, as determined through the process of routine optimization. The skilled artisan would have been motivated to do so because Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success as Lacy provides a proof-of-concept that L-methionine can be successfully incorporated into antibody-containing pharmaceutical compositions.
(19.1) Claims 1, 11, 31, 36, 42, 54, 214-217, 219-223, 225, and 227 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-201 of co-pending Application No. 19/157,282.
The co-pending reference application claims methods of treatment comprising the step of administering a pharmaceutical composition comprising an anti-TL1A antibody (e.g., co-pending claims 1-12). Co-pending claims 13-17 recite that the antibody is administered as a pharmaceutical composition with a concentration of antibody that is greater than 150 mg/mL or is about 150 mg/ml to about 250 mg/mL, pertinent to claims 1, 223, 225, and 227. Co-pending claims 20-23 recite that the total volume is less than or equal to 2.0 mL, relevant to claim 214. Co-pending claims 24-26 recite that the viscosity is less than 20 cP, further relevant to claim 1. Co-pending claims 27-28 recites that the percentage antibody aggregation in the pharmaceutical composition is less than about 5%, relevant to claim 11.
Co-pending claims 29-33 recite that the composition comprises about 0.01% to about 0.02% polysorbate-20, relevant to claims 1, 11, 31, 215, 223, 225, and 227. Co-pending claims 34-40 recite that the pharmaceutical composition comprises about 10 mM to about 100 mM NaCl, or about 40 mM NaCl, pertinent to claims 1, 11, 36, 216, 223, 225, and 227. Co-pending claims 41-48 recite that the pharmaceutical composition comprises sucrose as a stabilizer, at a concentration of about 50-300 mM or about 200-280 mM or 220-240 mM, relevant to claims 1, 11, 42, 217, 223, 225, and 227. Co-pending claims 49-53 recite that the pharmaceutical composition comprises acetate buffer at a concentration of about 10-50 mM or about 20 mM, relevant to claims 1, 11, 54, 219, 223, 225, and 227. Co-pending claims 54-57 recite that the pharmaceutical composition has a pH of about 4.5-7.5, or about 5.3, relevant to claims 1, 220-221, 223, 225, and 227.
Co-pending claims 198-201 recite that the anti-TL1A antibody comprises an identical combination of heavy chain and light chain CDRs as set forth in claims 1 and 225, and/or a VH comprising the amino acid sequence of SEQ ID NO: 104 (which shares 100% sequence identity to instant SEQ ID NO: 104) and a VL comprising the amino acid sequence of SEQ ID NO: 201 (which shares 100% sequence identity to instant SEQ ID NO: 201) as set forth in claims 222, 225, and 227.
(19.2) Claims 1, 11, 42, 218, and 223-228 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-201 of co-pending Application No. 19/157,282 as applied to claims 1, 11, 31, 36, 42, 54, 214-217, 219-223, 225, and 227 above, further in view of Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The teachings of the co-pending reference application are recited in the provisional NSDP rejection (19.1) above.
The co-pending reference application does not claim that the pharmaceutical composition specifically comprises L-methionine, formulated as set forth in the instant claims. However, this deficiency is remedied by Bansal and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Based on the further teachings of Bansal and Lacy, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to modify the anti-TL1A antibody formulation described in the co-pending claims, such that the formulation further comprises 1-50 mM, e.g., 25 mM, L-methionine, as determined through the process of routine optimization. The skilled artisan would have been motivated to do so because Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success as Lacy provides a proof-of-concept that L-methionine can be successfully incorporated into antibody-containing pharmaceutical compositions.
(20) Claims 223-224 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of co-pending Application No. 19/336,225 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The co-pending reference application claims a method of treating IBD that comprises administering a neutralizing anti-TL1A antibody comprising three defined heavy chain CDRs and three defined light chain CDRs (e.g., co-pending claims 12-19).
The co-pending reference application does not claim that the pharmaceutical antibody composition administered in the method specifically comprises a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the co-pending claims, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(21) Claims 223-224 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 10-15, 17, 19-20, 22-23, and 25-32 of co-pending Application No. 19/418,272 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The co-pending reference application claims a method of decreasing activity or expression of TL1A in a subject having IBD, Crohn’s disease, or ulcerative colitis, which comprises administering an anti-TL1A antibody set forth in Table 1 (pages 47-48) of the co-pending specification (e.g., claims 19, 23, 25).
The co-pending reference application does not claim that the pharmaceutical antibody composition administered in the method specifically comprises a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the co-pending claims, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
(22) Claims 1, 11, 31, 36, 42, 54, and 214-228 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 7-8, 11, 14-15, 31, 43, 47, 61-62, 66, 76, 95, and 98 of co-pending Application No. 19/485,687 in view of Kang (BioProcess International (2016) 14(4): 40-45; supra), Parshad (US 2013/0028907 A1; supra), Bansal (WO 2016/109822 A1; supra) and Lacy (U.S. Patent No 7,700,739; supra).
The co-pending reference application claims a method of treating an inflammatory disease by administering an inhibitor of TL1A, wherein said inhibitor is an anti-TL1A antibody comprising an identical combination of heavy chain and light chain CDRs as set forth in instant claims 1 and 225, and comprising the same framework and/or VH/VL sequences/structures as set forth in instant claims 222 and 227 (e.g., co-pending claims 1, 66, 76).
The co-pending reference application does not claim that the pharmaceutical antibody composition administered in said treatment method specifically comprises a surfactant, a salt, a stabilizer, and a buffering agent which are formulated as set forth in the instant claims. However, this deficiency is remedied by Kang, Parshad, Bansal, and Lacy, the teachings of whom are set forth in the 35 U.S.C. § 103 rejections above.
Taken together, it would have been obvious to one of ordinary skill in the art, before the filing date of the instantly claimed invention, to arrive an anti-TL1A antibody formulation comprising an anti-TL1A antibody such as that described in the co-pending claims, wherein the formulation further comprises 10-50 mM (e.g., 20 mM) NaOAc, 50-300 mM of a stabilizer (e.g., 220 mM sucrose), 10-100 mM (e.g., 40 mM) NaCl, 0.01% (v/v) polysorbate-20, and 25-50 mM L-methionine, and wherein the pH is 5.3, through the process of routine optimization. The skilled artisan would have been motivated to do so because Kang teaches that (1) commonly used buffers such as acetate keep pH levels of antibody formulations between 4.7 and 7.4, without significantly influencing the mAb’s stability; (2) polysorbate-20 is among the most common surfactants used in antibody formulations; and (3) sugars (e.g., sucrose) provide bulk for lyophilized formulations and serve as stabilizing agents for therapeutic proteins. Further, Bansal teaches that antioxidant methionine reduces viscosity and prevents antibody aggregation, which are both advantageous in the formulation of antibody-containing pharmaceutical compositions, and Lacy further provides that L-methionine can act as a stabilizer. There would have been a reasonable expectation of success because one of ordinary skill in the art would have recognized that each of the possible excipients within each category (surfactants, sugars, salts, buffers) have utility for the same respective purposes and are functionally equivalent variants, and Parshad provides a proof-of-concept that these components may be combined to formulate stable, low-viscosity antibody compositions comprising a higher concentration (e.g., 100 mg/mL or 200 mg/mL) of protein, and that the inclusion of an antioxidant does not impact the overall stability of pharmaceutical antibody compositions.
Conclusion
No claims are allowed.
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/ELIZABETH A SHUPE/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
