DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendment
The preliminary amendment filed 07/19/2024 is acknowledged. Claims 3-11, 13-16, 19 and 22 are amended and claims 17, 18 and 21 are newly canceled. No restriction is being imposed in this case. Claims 1-16, 19, 20, 22 and 23 are under examination.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. The priority date of the instant claims is 10/15/2021.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 5 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. Description of examples or preferences is properly set forth in the specification rather than the claims. If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim (see MPEP 2173.05(d)). Regarding claim 5, the phrase “preferably” renders the claim indefinite because it is unclear whether the limitation, “about 40-60 mg/ml” following the phrase is part of the claimed invention or meant only to illustrate a range within the 0.5-200 mg/ml range.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 19 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
Claim 19 recites a method of treating OX40-associated disease in a subject in need thereof comprising administering the pharmaceutical formulation of claim 1. Claim 1, from which claim 19 depends, stipulates that the pharmaceutical composition comprises a monoclonal anti-OX40 antibody. Using the instant specification as a lexicon, the encompassed monoclonal anti-OX40 antibody is an antagonist antibody that “can block the binding of OX40 ligand to OX40 to prevent the trimerization of OX40, and hence to inhibit T cell activation and related inflammatory responses induced by OX40 activation (see paragraphs [00146]-[00146]). Thus, the specification discloses a limited number of antagonist anti-OX40 antibodies. Using the instant specification as a lexicon, the patient population of claim 19 encompass those requiring treatment with either an OX40 agonist or antagonist (see paragraph [00168]).
To provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. The specification discloses antagonist antibodies comprising the heavy chain CDRs set forth in SEQ ID NOs: 1-3 and have the heavy chain variable regions selected from the group consisting of SEQ ID NOs: 7, 9 and 10 and comprising light chain CDRs set forth in SEQ ID NOs: 4-6 and have the light chain variable regions selected from the group consisting of SEQ ID NOs: 8, 11 and 12. The specifications does not provide any guidance in terms of the structure of antibodies that agonize OX40, however. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). With the exception of treating conditions that require treatment with an antagonist OX40 monoclonal antibody the skilled artisan cannot envision the detailed chemical structure of the antibodies that would be required for treating illnesses that require an agonist antibody and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Notice for all US Patent Applications filed on or after March 16, 2013: 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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 16, 19, 20, 22 and 23 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lamhamedi-Cherradi et al. (WO2008106116). Lamhamedi-Cherradi et al. teach an antagonist antibody that binds to human OX40, wherein said antibody is monoclonal (see claims 1, 18). Lamhamedi-Cherradi et al. teach that the monoclonal anti-OX40 antibody comprises a buffer, which can be a citrate buffer, a stabilizer, which can be trehalose, mannitol, sorbitol, xylitol or sucrose and a surfactant, which can be polysorbate 80 or polysorbate 20 (see paragraphs [00192]-[00195]), thereby meeting the limitation of claim 1. Lamhamedi-Cherradi et al. also teaches treating an OX40 mediated disorder such as an inflammatory or autoimmune disease comprising administering said anti-OX40 antibody subcutaneously or intravenously, as well as a kit comprising said antibody formulation (claims 26-30; claims 43-44 and paragraphs [00223], [00236]), thereby meeting the limitations of claims 16, 19, 20, 22 and 23.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 5-12, 16, 19, 20, 22 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Lamhamedi-Cherradi et al. (WO2008106116) in view of Le (WO2016044334). The first factor to consider when making a rejection under 35 U.S.C. 103(a) is to determine the scope and contents of the prior art. Lamhamedi-Cherradi et al. teach an antagonist antibody that binds to human OX40, wherein said antibody is monoclonal (see claims 1, 18). Lamhamedi-Cherradi et al. teach that the monoclonal anti-OX40 antibody comprises a buffer, which can be a citrate buffer, a stabilizer, which can be trehalose, mannitol, sorbitol, xylitol or sucrose and a surfactant, which can be polysorbate 80 or polysorbate 20 (see paragraphs [00192]-[00195]), thereby meeting the limitation of claim 1. Lamhamedi-Cherradi et al. also teaches treating an OX40 mediated disorder such as an inflammatory or autoimmune disease comprising administering said anti-OX40 antibody subcutaneously or intravenously, as well as a kit comprising said antibody formulation (claims 26-30; claims 43-44 and paragraphs [00223], [00236]), thereby meeting the limitations of claims 16, 19, 20, 22 and 23.
The second factor to consider is to ascertain the differences between the prior art and the instant claims. Lamhamedi-Cherradi et al. do not teach the concentrations of antibody, buffer, stabilizer or surfactant or the overall pH of the formulation. Le teaches stable antibody formulations for antibodies that resist denaturation, degradation, precipitation and chemical instability during storage (see paragraphs [0004]; [0054]). Le teaches the concentration of the antibody may be between 30-90 mg/ml, including 50, 55 and 60 mg/ml (see paragraphs [0010]; [0239]); a pH of about 5.5-6.5 (see paragraph [0013]); a histidine buffer in a concentration of about 15-100 mM (see paragraphs [0011], [0019]), which overlaps with the amount recited in claim 7; trehalose as a stabilizer at different concentrations, for instance 2.0%, 4.0% and 8.0% w/v (see paragraph [0040]), also sucrose may be substituted for trehalose at a concentration of 6% w/v (see paragraphs [0245]; [0261]); and a surfactant such as polysorbate 20 or 80 at a concentration ranging from about 0.01%-0.1% w/v, including 0.02%-0.06%, 0.03% to 0.05% or 0.04% (see paragraphs [0067]; [0246]), thus meeting concentration limitations set forth in claims 5-12).
It would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention to modify the teachings of Lamhamedi-Cherradi et al. by using the pH and the concentrations of antibody, buffer, stabilizer and surfactant taught by Le because Le teaches how to formulate antibodies for increased stability and reduced degradation during storage (see paragraph [0250]). The person of ordinary skill in the art would have been motivated to increase storage and reduce aggregates because “proteins are larger and more complex than traditional organic and inorganic drugs [and for] a protein to remain biologically active, a formulation must preserve intact the conformational integrity of at least a core sequence of the protein's amino acids while at the same time protecting the protein's multiple functional groups from degradation” see paragraph [0004] of Le. Furthermore, the person of ordinary skill in the art could have reasonably expected success because the reference by Le “provide[s] stable aqueous pharmaceutical formulations” of monoclonal antibodies (see paragraph [0006]) and the skill in the art of antibody formulation was high.
Thus, the claims do not contribute anything non-obvious over the prior art.
Claims 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over Lamhamedi-Cherradi et al. and Le as applied to claims 1, 5-12, 16, 19, 20, 22 and 23 above, and further in view of Igawa (US 10,022,319, issued 07/17/2018). The first factor to consider when making a rejection under 35 U.S.C. 103(a) is to determine the scope and contents of the prior art. The combined teachings of Lamhamedi-Cherradi et al. and Le and how they meet the limitations of claims 1, 5-12, 16, 19, 20, 22 and 23 are outlined above in the preceding rejection and are hereby incorporated. The second factor to consider is to ascertain the differences between the prior art and the instant claims. The combined teachings of Lamhamedi-Cherradi et al. and Le do not teach that the buffer is glutamic acid & histidine buffer or aspartic acid & histidine buffer.
Igawa teaches a method for suppressing aggregation formation during storage of an antibody-comprising formulation by using aspartic acid or glutamic acid as a counter ion species to a histidine buffer in the formulation, wherein the pH of the formulation is 5.5 to 6.5, and wherein the concentration is 50 mg/ml (see claims 16 and 17). It would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention to modify the teachings of Lamhamedi-Cherradi et al. and Le by combining glutamic acid or aspartic acid to histidine buffer because Igawa teaches the addition of aspartic acid or glutamic acid result in “significantly higher stabilization effect” (see column 2, lines 44-67). The person of ordinary skill in the art would have been motivated to add glutamic acid or aspartic acid to histidine buffer as a counter-ion because it improves the formulation for subcutaneous administration (see column 4, lines 18-35):
The present invention provides antibody-containing formulations that are superior in stability. The present invention can also provide highly-concentrated antibody-containing formulations by suppressing the aggregation formation in liquid and frozen formulations. The highly-concentrated antibody-containing formulations of the present invention can be stably stored in liquid or in frozen condition for a long period. Furthermore, the formulations of the present invention have an improved stability against freeze-thawing stress. In addition, in terms of osmotic pressure, stabilization can be achieved without increasing osmotic pressure, by using aspartic acid and glutamic acid rather than the conventionally used hydrochloric acid and acetic acid as counter-ion species to histidine, arginine, or tris(hydroxymethyl) aminomethane. It is advantageous to achieve stabilization without increasing the osmotic pressure, when one intends to produce almost isotonic, stable formulations, such as formulations for subcutaneous (SC) administration.
Furthermore, the person of ordinary skill in the art could have reasonably expected success because the skill in the art of antibody formulation was high.
Thus, the claims do not contribute anything non-obvious over the prior art.
Claims 1-4 are rejected under 35 U.S.C. 103 as being unpatentable over Yang et al. (WO2021209019, effectively filed 04/16/2021, prior to the instant effective filing date) in view of Le (WO2016044334). The first factor to consider when making a rejection under 35 U.S.C. 103(a) is to determine the scope and contents of the prior art. Yang et al. teach an anti-OX40 antibody having the identical heavy chain sequences set forth in SEQ ID NOs: 1-3 and light chain sequences set forth in SEQ ID NOs: 4-6, as well as a N297A variant in the Fc region. See the alignment between instant SEQ ID NOs: 1-3 and SEQ ID NO: 3 of Yang and colleagues:
Query Match 87.6%; Score 173.4; Length 120;
Best Local Similarity 41.8%;
Matches 33; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 SYWVD--------------NIYPSDSETHYNQKFKD------------------------ 22
||||| |||||||||||||||||
Db 31 SYWVDWVRQAPGQGLEWIGNIYPSDSETHYNQKFKDRVTMTVDTSTSTVYMELSSLRSED 90
Qy 23 --------SYGYYGTWFAY 33
|||||||||||
Db 91 TAVYYCARSYGYYGTWFAY 109
SEQ ID NO: 3 of Yang et al. also shares 100% sequence identity with instant SEQ ID NO: 9 (see p. 49). The alignment between instant SEQ ID NOs: 4-6 and SEQ ID NO: 9 of Yang is as follows:
Query Match 84.7%; Score 136.3; Length 111;
Best Local Similarity 39.7%;
Matches 31; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 RASESVDSSGNSFMH---------------RASNLES----------------------- 22
||||||||||||||| |||||||
Db 24 RASESVDSSGNSFMHWYQQKPGQPPKLLIYRASNLESGIPDRFSGSGSGTDFTLTISSVQ 83
Qy 23 ---------QQSNEDPWT 31
|||||||||
Db 84 AEDVAVYYCQQSNEDPWT 101
SEQ ID NO: 9 of Yang et al. also shares 100% sequence identity with instant SEQ ID NO: 11 (see p. 49).
The second factor to consider is to ascertain the differences between the prior art and the instant claims. Yang et al. do not teach the anti-OX40 antibody is formulated with a buffer, stabilizer or surfactant of. Le teaches stable antibody formulations for antibodies that resist denaturation, degradation, precipitation and chemical instability during storage (see paragraphs [0004]; [0054]). Le teaches a histidine buffer in a concentration of about 15-100 mM (see paragraphs [0011], [0019]); trehalose or sucrose as a stabilizer (see paragraphs [0040]; [0245]; [0261]) and a surfactant such as polysorbate 20 or 80 (see paragraphs [0067]; [0246]). It would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention to modify the teachings of Yang et al. by using the buffers, stabilizers and surfactants taught by Le because Le teaches how to formulate antibodies for increased stability and reduced degradation during storage (see paragraph [0250]). The person of ordinary skill in the art would have been motivated to increase storage and reduce aggregates because “proteins are larger and more complex than traditional organic and inorganic drugs [and for] a protein to remain biologically active, a formulation must preserve intact the conformational integrity of at least a core sequence of the protein's amino acids while at the same time protecting the protein's multiple functional groups from degradation” see paragraph [0004] of Le. Furthermore, the person of ordinary skill in the art could have reasonably expected success because the reference by Le “provide[s] stable aqueous pharmaceutical formulations” of monoclonal antibodies (see paragraph [0006]) and the skill in the art of antibody formulation was high.
Thus, the claims do not contribute anything non-obvious over the prior art.
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.
19/505,204
Claims 1-16, 19, 20, 22 and 23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-61 of copending Application No. 19/505,204 in view of Lamhamedi-Cherradi et al. (WO2008106116) and Le (WO2016044334). The claims of the reference application are drawn to a method of treating alopecia areata in a subject comprising administering to the subject by intravenous infusion a therapeutically effective amount of an anti-OX40 antibody or antigen-binding fragment thereof comprising a light chain variable region (VL) comprising VL CDR1, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs: 1, 2, and 3, respectively; and a heavy chain variable region (VH) comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs:4, 5 and 6, respectively, wherein the VL has the amino acid sequence of SEQ ID NO:7, 9, or 10, and the VH has the amino acid sequence of SEQ ID NO:8, 11, or 12, wherein the anti-OX40 antibody comprises the CH region of human IgG1 with N297A substitution.
The differences between the claim sets are as follows. The claims of the reference application are drawn to treatment methods rather than the antibody composition; however, the claims of the reference application encompass the same antibody. Further, the claims of the reference application are more detailed with respect to the full amino acid structure of the antibody, however the species anticipates the genus. Finally, the claims of the reference application do not recite the details of the instantly claimed antibody formulation.
Regarding the antibody formulation, Lamhamedi-Cherradi et al. teach a monoclonal antagonist antibody that binds to human OX40 that is formulated with a buffer, which can be a citrate buffer, a stabilizer, which can be trehalose, mannitol, sorbitol, xylitol or sucrose, and a surfactant, which can be polysorbate 80 or polysorbate 20, as well as a kit comprising said antibody formulation (see claims 1, 18, 43, 44; paragraphs [00192]-[00195]; [00223], [00236]). Le teaches stable antibody formulations for antibodies that resist denaturation, degradation, precipitation and chemical instability during storage (see paragraphs [0004]; [0054]). Le teaches the concentration of the antibody may be between 30-90 mg/ml, including 50, 55 and 60 mg/ml (see paragraphs [0010]; [0239]); a pH of about 5.5-6.5 (see paragraph [0013]); a histidine buffer in a concentration of about 15-100 mM (see paragraphs [0011], [0019]); trehalose as a stabilizer at different concentrations, for instance 2.0%, 4.0% and 8.0% w/v (see paragraph [0040]), also sucrose may be substituted for trehalose at a concentration of 6% w/v (see paragraphs [0245]; [0261]); and a surfactant such as polysorbate 20 or 80 at a concentration ranging from about 0.01%-0.1% w/v, including 0.02%-0.06%, 0.03% to 0.05% or 0.04% (see paragraphs [0067]; [0246]).
It would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention to formulate the antibody according to the pH and the concentrations of antibody, buffer, stabilizer and surfactant taught by Lamhamedi-Cherradi et al. and Le because they teach how to formulate antibodies for increased stability and reduced degradation during storage (see paragraph [0250]). The person of ordinary skill in the art would have been motivated to increase storage and reduce aggregates because “proteins are larger and more complex than traditional organic and inorganic drugs [and for] a protein to remain biologically active, a formulation must preserve intact the conformational integrity of at least a core sequence of the protein's amino acids while at the same time protecting the protein's multiple functional groups from degradation” see paragraph [0004] of Le. Furthermore, the person of ordinary skill in the art could have reasonably expected success because the teachings “provide stable aqueous pharmaceutical formulations” of monoclonal antibodies (see paragraph [0006] of Le) and the skill in the art of antibody formulation was high.
Thus, when read in light of the prior art teachings of Lamhamedi-Cherradi et al. and Le, the instant claims are not patentably distinct from those of the reference application.
This is a provisional nonstatutory double patenting rejection.
19,621,166
Claims 1-16, 19, 20, 22 and 23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-63 of copending Application No. 19,621,166 in view of Le (WO2016044334). The claims of the reference application are drawn to a pharmaceutical composition comprising (A) an anti-OX40 antibody or antigen-binding fragment thereof comprising (1) a light chain variable region (VL) comprising VL CDRI, VL CDR2, and VL CDR3 having the amino acid sequences of SEQ ID NOs:1, 2, and 3, respectively; and(2) a heavy chain variable region (VH) comprising VH CDR1, VH CDR2, and VH CDR3 having the amino acid sequences of SEQ ID NOs:4, 5 and 6, respectively; and (B) a pharmaceutically acceptable carrier comprising a glutamic/histidine buffer, proline, and polysorbate 80, wherein the VL has the amino acid sequence of SEQ ID NO: 7, 9, or 10, and the VH has the amino acid sequence of SEQ ID NO: 8, 11, or 12, wherein the anti-OX40 antibody is a humanized IgG1 antibody with a N297A substitution, wherein the anti-OX40 antibody or antigen-binding fragment is at a concentration ranging from 80 to 180 mg/mL, wherein the glutamic/histidine buffer is at a concentration ranging from 10 to 50 mM, wherein the polysorbate 80 is at a concentration ranging from 0.0-0.03% (w/v), wherein the pH ranges from 4.8 to 6.8, from 5.0 to 6.5, from 5.0 to 6.0 or from 5.0 to 5.8, and a kit therefor. Finally, the claims of the reference application recite a method of treating an OX40-associated disease comprising administering a therapeutically effective amount of said pharmaceutical composition.
The differences between the instant claims and those of the reference application are as follows. The claims of the reference application are more detailed with respect to the full amino acid structure of the antibody, however the species anticipates the genus. In addition, the claims of the reference application do not mention the same stabilizers as those of the instant claims. Le teaches formulating antibodies into stable liquid formulations in which the concentration of the antibody may be between 30-90 mg/ml, including 50, 55 and 60 mg/ml (see paragraphs [0010]; [0239]); a pH of about 5.5-6.5 (see paragraph [0013]); trehalose as a stabilizer at different concentrations, for instance 2.0%, 4.0% and 8.0% w/v (see paragraph [0040]), also sucrose may be substituted for trehalose at a concentration of 6% w/v (see paragraphs [0245]; [0261]); and a surfactant such as polysorbate 20 or 80 at a concentration ranging from about 0.01%-0.1% w/v, including 0.02%-0.06%, 0.03% to 0.05% or 0.04% (see paragraphs [0067]; [0246]).
It would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention to formulate the antibody according to the pH using the trehalose or sucrose as a stabilizer as taught by Le because they result in formulations having increased stability and reduced degradation during storage (see paragraph [0250]). The person of ordinary skill in the art would have been motivated to increase storage and reduce aggregates because “proteins are larger and more complex than traditional organic and inorganic drugs [and for] a protein to remain biologically active, a formulation must preserve intact the conformational integrity of at least a core sequence of the protein's amino acids while at the same time protecting the protein's multiple functional groups from degradation” see paragraph [0004] of Le. Furthermore, the person of ordinary skill in the art could have reasonably expected success because the teachings “provide stable aqueous pharmaceutical formulations” of monoclonal antibodies (see paragraph [0006] of Le) and the skill in the art of antibody formulation was high.
Thus, when read in light of the prior art teachings of Le, the instant claims are not patentably distinct from those of the reference application.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA M BORGEEST whose telephone number is (571)272-4482. The examiner can normally be reached M-F 9-5:30 EDT.
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/CHRISTINA M BORGEEST/Primary Examiner, Art Unit 1675
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