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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 01/29/2026 has been entered.
Claims 50, 53, 76, 77, 79 and 80 are amended; claims 54, 57, 58, 61, 62, 65, 66, 69, 70, 73-75, 78 and 81-83 are newly canceled and claims 84 and 85 are new.
Claims 50, 53, 76, 77, 79, 80, 84 and 85 are under examination.
Objections/Rejections Withdrawn
Any previous rejections over claims 54, 57, 58, 61, 62, 65, 66, 69, 70, 73-75, 78 and 81-83 are hereby withdrawn in response to Applicant’s cancelation of those claims.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Objections
The objection to claims 77 and 80 for minor informalities is withdrawn in response to Applicant’s amendment to the claims deleting the extra sentence.
Claim Rejections - 35 USC § 112(d)
The rejection of claim 80 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends is withdrawn in response to Applicant’s amendment of claim 80 to delete a single dose of 120 mg of galcanezumab-gnlm, which did not properly limit independent claim 53.
Claim Rejections - 35 USC § 112(a)
The rejection of claims 77 and 80 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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in response to Applicant’s amendment. Specifically, the claims have deleted reference to the prefilled syringe or pen comprising the recited anti-CGRP antibody in a pH range of 5.3-6.3, which did not have explicit, implicit or inherent support in the instant specification.
Claim Rejections - 35 USC § 103
The rejection of claims 50 and 76 as being unpatentable over Bigal et al. (US2015/0266948, effectively filed 03/21/2014), Kaisheva (US2003/0138417 and Allan et al. (US20110305711—on IDS filed 03/17/2022) is withdrawn in response to Applicant’s amendment and upon further consideration. Independent claim 50 recites preventing episodic or chronic migraine comprising administering an anti-CGRP antibody subcutaneously at a loading dose of 240 mg followed by monthly subcutaneous doses of 120 mg of an anti-CGRP antibody as set forth in SEQ ID NOs: 3 and 4, wherein the antibody is present in the pharmaceutical composition at a concentration of 120 mg/mL, has a pH ranging from about 5.7 to 6.0 and comprises
A histidine buffer at a concentration of about 10 mM;
NaCl at at concentration of about 150 mM; and
Polysorbate 80 at a concentration of about 0.05% (w/v).
Bigal et al. teach treating migraines and cluster headaches comprising administering an anti-CGRP antibody at doses ranging from 100-2000 mg (see abstract; paragraphs [0015], [0019]; [0179]; claims 1-2, 42). While Bigal et al. suggest loading and maintenance doses, (see paragraphs [0187]; [0203]-[0204]), these suggest more than 1,600 possible loading/maintenance dose combinations. See also pages 5-6 of the Remarks filed 01/29/2026. There is nothing in Bigal et al. that specifically points to selecting a loading dose of 240 mg and a monthly dose of 120 mg.
Double Patenting
The rejection of claims 50 and 76 on the ground of nonstatutory double patenting as being unpatentable over the following is withdrawn in response to Applicant’s amendment and upon further consideration.
Claims 1-8 of U.S. Patent No. 9,073,991 in view of Bigal et al. and Kaisheva.
Claims 1-7 of U.S. Patent No. 9,505,838 in view of Bigal et al. and Kaisheva.
As with the rejection under 35 USC 103, there is nothing in the claims of either of the reference patents in combination with Bigal et al. and Kaisheva that specifically points to selecting a loading dose of 240 mg and a monthly dose of 120 mg.
Rejections Maintained/New Rejection
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.
The rejection of claims 53 and 79 as being unpatentable over Bigal et al. (US2015/0266948, effectively filed 03/21/2014), Kaisheva (US2003/0138417 and Allan et al. (US20110305711—on IDS filed 03/17/2022) is maintained for reasons of record and the following. In addition, claims 77, 80 and 85 are hereby included in this rejection. Amended claim 53 recites a method to treat cluster headache comprising administering a monthly subcutaneous dose of 300 mg of an anti-CGRP antibody in a pharmaceutical formulation comprising histidine buffer at a concentration of about 10 mM, NaCl at a concentration of about 150 mM, PS-80 at a concentration of about 0.05% (w/v), and having a pH of about 5.7 to 6.0, wherein the anti-CGRP antibody comprises a LC given by the amino acid sequence of SEQ ID NO: 3 and a HC given by the amino acid sequence of SEQ ID NO: 4 and is present in the formulation at a concentration of 100 mg/ml. New claim 85 recites that the pH of the formulation is about 5.8.
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. Bigal et al. teach treating migraines and cluster headaches comprising administering an anti-CGRP antibody at doses ranging from 100-2000 mg (see abstract; paragraphs [0015], [0019]; [0179; claims 1-2, 42). Bigal et al. suggests an “exemplary dosing regimen” of 300 mg once monthly (see paragraph [0187]). While this passage of Bigal and colleagues suggests about 15 monthly doses, one having ordinary skill in the art could envisage this species within the genus, which is not large (see MPEP 2144.08(II)(A)(4)(a)). Bigal et al. suggest that the antibody may be formulated at concentrations ranging from 10 mg/mL to 250 mg/mL (see paragraph [0167]). Bigal et al. contemplates an anti-CGRP pharmaceutical formulation at a pH of 5.5 or 6.0 that comprises histidine, NaCl and polysorbate 80 (PS-80) in a prefilled syringe (see paragraphs [0151]-[0152]; [0166]-[0167]; [0173]; [0175]-[0176]; [0179]; [0180]; [0183]; [0186]-[0188]). Bigal et al. teach histidine is present concentrations of 1-20mM, 20mM, or 0.1-100mM (see paragraph [0151]), which encompasses the recited amount of 10 mM in amended claim 53. See MPEP 2144.04(I), which states that “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”.
The second factor to consider is to ascertain the differences between the prior art and the instant claims. Bigal et al. do not teach the concentrations of the NaCl or PS-80, although they do suggest PS-80 concentrations of 0.1, 0.15, 0.2, 0.25 and 0.3 mg/ml (see paragraphs [0151]; [0167]-[0169]; [0171]; [0174]-[0179]; [0181]; [0184]-[0186]), which represents 0.01% (w/v), 0.015 (w/v), 0.02 (w/v), 0.025 (w/v) and 0.03% (w/v). Further, Bigal et al. do not explicitly teach the anti-CGRP antibody comprising the full light chain set forth in SEQ ID NO: 3 and the full heavy chain set forth in SEQ ID NO: 4, although the antibody disclosed therein is encompassed by the instant antibody comprising SEQ ID NOs: 3 and 4, respectively:
US-17-554-713-3
Query Match 100.0%; Score 565; DB 1; Length 214;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCRASKDISKYLNWYQQKPGKAPKLLIYYTSGYHSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTITCRASKDISKYLNWYQQKPGKAPKLLIYYTSGYHSGVPS 60
Qy 61 RFSGSGSGTDFTLTISSLQPEDFATYYCQQGDALPPTFGGGTKVEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLQPEDFATYYCQQGDALPPTFGGGTKVEIK 107
US-17-554-713-4
Query Match 100.0%; Score 627; DB 1; Length 445;
Best Local Similarity 100.0%;
Matches 119; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGSSVKVSCKASGYTFGNYWMQWVRQAPGQGLEWMGAIYEGTGKTVY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGSSVKVSCKASGYTFGNYWMQWVRQAPGQGLEWMGAIYEGTGKTVY 60
Qy 61 IQKFADRVTITADKSTSTAYMELSSLRSEDTAVYYCARLSDYVSGFGYWGQGTTVTVSS 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 IQKFADRVTITADKSTSTAYMELSSLRSEDTAVYYCARLSDYVSGFGYWGQGTTVTVSS 119
(i) Regarding concentrations, Kaisheva teaches that stable liquid pharmaceutical formulations for immunoglobulin G antibodies comprise NaCl at 75-150 mM and PS-80 at 0.01 % to about 0.05% (w/v—see paragraphs [0052]; [0054]; [0068]; [0093]; claims 12-13). Regarding pH, Kaisheva teaches a range of 5.5-6.5, and exemplifies a pH of 6 (see claims, 2, 7 and the examples at paragraphs [0094]-[0107]). 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 Bigal et al. by formulating the anti-CGRP antibody in 75-150 mM NaCl and 0.05 (w/v) PS-80 because Kaisheva et al. teach that 150 mM NaCl and 0.05% polysorbate 80 represent the most stable excipient concentrations (see paragraph [0093]). In addition, formulations at a pH of 6.0 remained stable at room temperature for a year (see paragraph [0102]).
In addition, it is obvious to optimize excipient concentrations and pH within prior art conditions. The MPEP 2144.05(II)(A) states:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation… The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.
Further, as noted by the United States Supreme Court, if a person of ordinary skill can implement a predictable variation, §103 likely bars its patentability. For the same reason, if a technique has been used to improve one method (i.e., Kaisheva stabilizing pharmaceutical formulations of antibodies), and a person of ordinary skill would recognize that it would improve similar methods (i.e., Bigal’s pharmaceutical formulation of an antibody) in the same way, using the technique is obvious unless its actual application is beyond his or her skill (KSR, 127 S. Ct. at 1740). “When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product is not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show it was obvious under 35 U.S.C. 103.” KSR Int'l Co. v. Teleflex Inc., 127 S.Ct. 1727, 1742, 82USPQ2d 1385, 1396 (2007). The person of ordinary skill in the art would have been motivated to formulate the anti-CGRP antibody using the excipient concentrations and pH taught in Kaisheva because of the increased stability in the antibody formulation. Furthermore, the person of ordinary skill in the art could have reasonably expected success for this reason.
(ii) Regarding the anti-CGRP antibody, Allan requires the anti-CGRP antibody to comprise SEQ ID NOs: 29 and 34 (claim 15), the sequences of which are identical to instant SEQ ID NOs: 3 and 4, respectively.
SEQ ID NO: 3:
US-13-154-538-29
(NOTE: this sequence has 30 duplicates in the database searched.
See complete list at the end of this report)
Sequence 29, US/13154538
Publication No. US20110305711A1
GENERAL INFORMATION
APPLICANT: ALLAN, Barrett
APPLICANT: BENSCHOP, Robert J.
APPLICANT: CHAMBERS, Mark G.
APPLICANT: DARLING, Ryan J.
TITLE OF INVENTION: CGRP ANTIBODIES
FILE REFERENCE: X-18827
CURRENT APPLICATION NUMBER: US/13/154,538
CURRENT FILING DATE: 2011-06-07
PRIOR APPLICATION NUMBER: 61/353323
PRIOR FILING DATE: 2010-06-10
NUMBER OF SEQ ID NOS: 43
SEQ ID NO 29
LENGTH: 214
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic Construct
Query Match 100.0%; Score 1118; Length 214;
Best Local Similarity 100.0%;
Matches 214; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCRASKDISKYLNWYQQKPGKAPKLLIYYTSGYHSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTITCRASKDISKYLNWYQQKPGKAPKLLIYYTSGYHSGVPS 60
Qy 61 RFSGSGSGTDFTLTISSLQPEDFATYYCQQGDALPPTFGGGTKVEIKRTVAAPSVFIFPP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLQPEDFATYYCQQGDALPPTFGGGTKVEIKRTVAAPSVFIFPP 120
Qy 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
Qy 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
||||||||||||||||||||||||||||||||||
Db 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
And SEQ ID NO: 4:
RESULT 1
US-13-154-538-34
(NOTE: this sequence has 27 duplicates in the database searched.
See complete list at the end of this report)
Sequence 34, US/13154538
Publication No. US20110305711A1
GENERAL INFORMATION
APPLICANT: ALLAN, Barrett
APPLICANT: BENSCHOP, Robert J.
APPLICANT: CHAMBERS, Mark G.
APPLICANT: DARLING, Ryan J.
TITLE OF INVENTION: CGRP ANTIBODIES
FILE REFERENCE: X-18827
CURRENT APPLICATION NUMBER: US/13/154,538
CURRENT FILING DATE: 2011-06-07
PRIOR APPLICATION NUMBER: 61/353323
PRIOR FILING DATE: 2010-06-10
NUMBER OF SEQ ID NOS: 43
SEQ ID NO 34
LENGTH: 445
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic Construct
Query Match 100.0%; Score 2366; Length 445;
Best Local Similarity 100.0%;
Matches 445; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGSSVKVSCKASGYTFGNYWMQWVRQAPGQGLEWMGAIYEGTGKTVY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGSSVKVSCKASGYTFGNYWMQWVRQAPGQGLEWMGAIYEGTGKTVY 60
Qy 61 IQKFADRVTITADKSTSTAYMELSSLRSEDTAVYYCARLSDYVSGFGYWGQGTTVTVSSA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 IQKFADRVTITADKSTSTAYMELSSLRSEDTAVYYCARLSDYVSGFGYWGQGTTVTVSSA 120
Qy 121 STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 STKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSG 180
Qy 181 LYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVF 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 LYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEAAGGPSVF 240
Qy 241 LFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYR 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 LFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYR 300
Qy 301 VVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 VVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKN 360
Qy 361 QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGN 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 QVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGN 420
Qy 421 VFSCSVMHEALHNHYTQKSLSLSLG 445
|||||||||||||||||||||||||
Db 421 VFSCSVMHEALHNHYTQKSLSLSLG 445
It would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention that the antibody taught by Allen et al. is an obvious variant of that taught in Bigal et al. because the sequences taught therein comprise instant SEQ ID NOs: 1 and 2. The person of ordinary skill in the art would have been motivated to administer antibodies comprising SEQ ID NOs: 3 and 4 because Allan et al. teach that they are suitable for treating migraines (see paragraphs [0049], [0061]-[0063]; claim 25). For these reasons as well, the person of ordinary skill in the art could have reasonably expected success.
Response to Arguments
Applicant argues at pages 5-6 that Bigal et al. teach broad ranges that do not teach or suggest a loading dose of 240 mg followed by a monthly 120 mg dose, and then asserts at p. 6 “[s]imilarly for cluster headaches, nothing teaches selecting 300 mg monthly doses from the vast array of possibilities.
This argument has been fully considered, but is not found persuasive. Applicant’s arguments persuasively address why one having ordinary skill in the art would not select a loading dose of 240 mg anti-CGRP antibody followed by monthly subcutaneous doses of 120 mg, however, claims 53, 79, 80 and 85 do not recite this limitation, therefore this argument addresses limitations not present in the claims. Bigal et al. suggest prevention of episodic or migraine and treatment of cluster headache with an antibody that shares the same heavy and light chain variable domains as that of the anti-CGRP antibody recited in the instant claims. Furthermore, Bigal et al. explicitly suggest a monthly dose 300 mg of the anti-CGRP antibody (paragraph [0187]), which is selected from a finite list of a finite number of identified, predictable solutions (doses). Therefore, Bigal et al. explicitly disclose the same dose recited in independent claim 53 for the treatment of cluster headache.
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.
The rejections of claims 53 and 79 on the ground of nonstatutory double patenting as being unpatentable over the following is maintained for reasons of record and the following. In addition, claims 80 and 85 are hereby included in these rejections.
Claims 1-8 of U.S. Patent No. 9,073,991 in view of Bigal et al. and Kaisheva.
The reference ‘991 patent is drawn to a pharmaceutical composition comprising a human engineered calcitonin gene related peptide (CGRP) antibody having the sequences set forth in SEQ ID NOs: 19, 24, 29 and 34, which share the same sequences as those of instant SEQ ID NOs: 1-4, respectively, and a pharmaceutically acceptable carrier, diluent, or excipient.
Claims 1-7 of U.S. Patent No. 9,505,838 in view of Bigal et al. and Kaisheva.
The reference ‘838 patent is drawn to a method of treating migraines comprising administering a human engineered CGRP antibody having the sequences set forth in SEQ ID NOs: 19, 24, 29 and 34, which share the same sequences as those of instant SEQ ID NOs: 1-4, respectively.
Regarding the dose of 300 mg, Bigal et al. teach treating migraines and cluster headaches comprising administering an anti-CGRP antibody at doses ranging from 100-2000 mg (see abstract; paragraphs [0015], [0019]; [0179; claims 1-2, 42). Bigal et al. suggests an “exemplary dosing regimen” of 300 mg once monthly (see paragraph [0187]). While this passage of Bigal and colleagues suggests about 15 monthly doses, one having ordinary skill in the art could envisage the species within this genus, which is not large (see MPEP 2144.08(II)(A)(4)(a)). Bigal et al. suggest that the antibody may be formulated at concentrations ranging from 10 mg/mL to 250 mg/mL (see paragraph [0167]). Bigal et al. contemplates an anti-CGRP pharmaceutical formulation at a pH of 5.5 or 6.0 that comprises histidine, NaCl and polysorbate 80 (PS-80) in a prefilled syringe (see paragraphs [0151]-[0152]; [0166]-[0167]; [0173]; [0175]-[0176]; [0179]; [0180]; [0183]; [0186]-[0188]). Bigal et al. teach histidine is present concentrations of 1-20mM, 20mM, or 0.1-100mM (see paragraph [0151]), which encompasses the recited amount of 10 mM in amended claim 53. See MPEP 2144.04(I), which states that “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”.
Regarding concentrations, Kaisheva teaches that stable liquid pharmaceutical formulations for immunoglobulin G antibodies comprise NaCl at 75-150 mM and PS-80 at 0.01 % to about 0.05% (w/v—see paragraphs [0052]; [0054]; [0068]; [0093]; claims 12-13). Regarding pH, Kaisheva teaches a range of 5.5-6.5, and exemplies a pH of 6 (see claims, 2, 7 and the examples at paragraphs [0094]-[0107]). 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 Bigal et al. by formulating the anti-CGRP antibody in 75-150 mM NaCl and 0.05 (w/v) PS-80 because Kaisheva et al. teach that 150 mM NaCl and 0.05% polysorbate 80 represent the most stable excipient concentrations (see paragraph [0093]). In addition, formulations at a pH of 6.0 remained stable at room temperature for a year (see paragraph [0102]).
In addition, it is obvious to optimize excipient concentrations and pH within prior art conditions. The MPEP 2144.05(II)(A) states:
Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation… The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.
Further, as noted by the United States Supreme Court, if a person of ordinary skill can implement a predictable variation, §103 likely bars its patentability. For the same reason, if a technique has been used to improve one method (i.e., Kaisheva stabilizing pharmaceutical formulations of antibodies), and a person of ordinary skill would recognize that it would improve similar methods (i.e., Bigal’s pharmaceutical formulation of an antibody) in the same way, using the technique is obvious unless its actual application is beyond his or her skill (KSR, 127 S. Ct. at 1740). “When there is a design need or market pressure to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product is not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try might show it was obvious under 35 U.S.C. 103.” KSR Int'l Co. v. Teleflex Inc., 127 S.Ct. 1727, 1742, 82USPQ2d 1385, 1396 (2007). The person of ordinary skill in the art would have been motivated to formulate the anti-CGRP antibody using the excipient concentrations and pH taught in Kaisheva because of the increased stability in the antibody formulation. Furthermore, the person of ordinary skill in the art could have reasonably expected success for this reason.
Response to Arguments
Applicant argues at p. 8 that for the same reasons as discussed regarding the rejection under 35 USC 103, Applicant disagrees with the rejections and requests their withdrawal.
This argument has been fully considered, but is not found persuasive. For the same reasons as outlined above in the Response to Arguments section regarding the rejection under 35 USC 103, hereby incorporated, the rejections are maintained.
Double Patenting – New Rejection
Claims 53, 79, 80 and 85 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 42-60 and 64-69 of copending Application No. 17/883,072 in view of Bigal et al. (US2015/0266948). Both claim sets recite an anti-CGRP antibody comprising a prefilled syringe comprising a pharmaceutical formulation comprising an anti-CGRP antibody having the amino acid sequences set forth in SEQ ID NO: 3 and SEQ ID NO: 4, 10 mM of histidine buffer, 150 mM of NaCl, 0.05% (w/v) of polysorbate-80 (PS-80) at a pH ranging from 5.5 to 6, including 5.8. Further, the claims of the reference application recite the formulation comprises 100 mg/ml of the anti-CGRP antibody and contemplates the formulation is suitable for subcutaneous injection.
The difference between the claim sets are as follows. The claims of the reference application are drawn to the anti-CGRP antibody, rather than a method of treating cluster headache. Nevertheless, this would have been obvious in light of the teachings of the prior art of Bigal et al, who teach treating migraines and cluster headaches comprising administering an anti-CGRP antibody at doses ranging from 100-2000 mg (see abstract; paragraphs [0015], [0019]; [0179; claims 1-2, 42). Bigal et al. suggests an “exemplary dosing regimen” of 300 mg once monthly (see paragraph [0187]). While this passage of Bigal and colleagues suggests about 15 monthly doses, one having ordinary skill in the art could envisage this genus, which is not large (see MPEP 2144.08(II)(A)(4)(a)). See also MPEP 2144.04(I), which states that “[i]n the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”. Thus, in light of the teachings of Bigal et al., the instant claims are not patentably distinct from those of the ‘072 application.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Claims 50, 76, 77 and 84 are allowed and claims 53, 79, 80 and 85 are rejected.
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/CHRISTINA M BORGEEST/Primary Examiner, Art Unit 1675