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 .
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on June 11, 2026 has been entered.
RESPONSE TO AMENDMENT
Status of Application/Amendments/claims
3. Applicant’s amendment filed June 11, 2026 and July 15, 2026 is acknowledged. Claims 1-41, 61-63 and 69 are canceled. Claims 42, 59-60, 64-65, and 68 are amended. Claims 42-60 and 64-68 are pending in this application and under examination in this office action.
4. Applicant’s arguments filed on June 11, 2026 and July 15, 2026 have been fully considered but they are not deemed to be persuasive for the reasons set forth below.
Claim Rejections/Objections Withdrawn
5. The rejection of claim 69 under 35 U.S.C. 103 as being unpatentable over Bigal et al. (US2015/0266948) in view of Allan et al. (US2011/0305711) and Kaisheva (US 2003/0138417) is moot because the claim is canceled.
The rejection of claim 69 on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of US11498959 in view of Bigal et al. (US2015/0266948), Allan et al. (US2011/0305711) and Kaisheva (US 2003/0138417) is moot because the claim is canceled.
Claim Rejections/Objections Maintained
In view of the amendment filed on June 11, 2026 and July 15, 2026, the following rejections are maintained.
Claim Rejections - 35 USC § 103
6. 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 42-60 and 64-68 stand rejected under 35 U.S.C. 103 as being unpatentable over Bigal et al. (US2015/0266948) in view of Allan et al. (US2011/0305711) and Kaisheva (US2003/0138417). The rejection is maintained for the reasons of record and the rejection set forth below.
Claims 42-60 as amended are drawn to a prefilled syringe or pen comprising a pharmaceutical formulation comprising:
(a) 50-160 mg/mL of an anti-CGRP antibody;
(b) 5-20 mM of histidine buffer;
(c) 50-200 mM of NaCl;
(d) 0.03-0.07% (w/v) of polysorbate-80 (PS-80); and
(e) a pH of 5.0-6.5, and
wherein the anti-CGRP antibody comprises two light chains (LCs) and two heavy chains (HCs), the amino acid sequence of each LC given by SEQ ID NO: 3 and the amino acid sequence of each HC given by SEQ ID NO: 4;
wherein the anti-CGRP antibody is present at a concentration sufficient to protect the PS-80 from oxidation without the addition of a separate antioxidant , and wherein the pharmaceutical composition does not comprise any additional antioxidants.
Claims 64-68 as amended are drawn to a prefilled syringe or pen comprising a pharmaceutical formulation as set forth above but comprising:
(a) 100 or 120 mg/mL of the same anti-CGRP antibody;
(b) 10 mM of histidine buffer;
(c) 150mMof NaCl;
(d) 0.05% (w/v) of polysorbate-80 (PS-80); and
(e) a pH from 5.5 to 6.
Response to Arguments
On p. 7-8 of the response, Applicant argues that i) the anti-CGRP antibody itself at a concentration above 5mg/mL prevents PS-80 oxidation, and none of the cited references teach or suggest that the anti-CGRP antibody can prevent PS-80 oxidation. ii) Bigal’s formulations include dedicated antioxidants alongside PS-80 and cites para. [0167];[0172]-[0173],[0176],[0181] in support of the arguments. iii) Kaisheva teaches away from the claimed invention because Kaisheva teaches that histidine is less preferred…or adding an antioxidant..”. iv) The specification provides surprising and non-obvious results and cite Figure 1 and table 7, col. 16, lines 1-19 of the specification, and p. 23-24 of the office action of Application No. 15/578263 dated 04/07/2022 in support of the arguments. v) claims 64-68 are allowable because the specific antibody concentrations are not taught or specifically by the cited references. vi. routine optimization cannot extend to multiple variables co-optimization without guidance.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2141, MPEP2141-I, rationales identified by the Court in KSR (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, 82 USPQ2d 1385 (2007)), MPEP2141-II, the basic factual inquires of Graham v. John Deere Co.(Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966)),and MPEP §2141.01-2147.03, the cited references do render the claimed invention obvious because:
i. Each case is judged by its own merits.
ii. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). In this case, Allan is cited to support the limitations “LC given by SEQ ID NO:3 and HC given by SEQ ID NO:4”. Kaisheva does not teach away from the claimed invention. Kaisheva is cited to support the limitations “a concentration sufficient to protect the PS-80 from oxidation without the addition of a separate antioxidant” recited in independent claims 42 and 64 and different dose ranges recited in instant claims.
iii. The pre-filled syringe or pen disclosed by Bigal comprises a pharmaceutical formulation comprising an anti-CGRP antibody, histidine, NaCl, polysorbate 80 and a pH of 5-7, 5, 5.5 or 6 and does not comprise any additional antioxidants for administration because the stabilizers or antioxidants including EDAT or disodium EDTA dihydrate are optional (see para. [0151]). The concentration ranges of anti-CGRP antibody, histidine, NaCl, polysorbate 80 and the pH disclosed by Bigal are either within or overlapping with the claimed range of recited in instant claims.
Bigal (US 2015/0266948) teaches a prefilled receptacle ([0015]; [0063]; [0160]; [0208]; claim 17) comprising a pharmaceutical formulation comprising an anti-CGRP antibody, histidine, NaCl, polysorbate 80 and a pH of 5-7, 5, 5.5 or 6 and does not comprise any additional antioxidants for administration because the stabilizers or antioxidants including EDAT or disodium EDTA dihydrate are optional (see para. [0151]; para. [0152]; abstract; paragraphs [0015]-[0019];[0027]; [0160]; [0166]-[0167]l [0171]; [0175]-[0176]; [0179]; [0181]; [0183]; [0186]-[0188];[0194]-[0196]; [0198]; [0201];[0204]; [0208] [0411], claims 1-2, 42).
In particular, the anti-CGRP antibody disclosed by Bigal is formulated at a concentration of 150 mg/mL, …10-150mg/ml, 10-100mg/ml, …50mg/ml, 75mg/ml, 100mg/ml, 125mg/ml, 150mgml, 175mg/ml…1-150mg/ml 1-250mg/ml, a dose ranging from 100-2000 mg or monthly doses of 125 mg (paragraphs [0015]-[0019];[0027]; [0166]-[0167]l [0171]; [0175]-[0176]; [0179]; [0181]; [0183]; [0186]-[0188];[0194]-[0196]; [0198]; [0201];[0204]; [0411], claims 1-2, 42), which are either within or overlapping with the claimed range of 50-160mg/ml, 100-160mg/ml, 100mg/ml or 120mg/ml recited in claims 42-45 and 64-65.
The histidine disclosed by Bigal is at a concentration of 1-20mM, 20mM, or 0.1-100mM (paragraphs [0151]; [0167]; [0173]; [0176]; [0179]-[0180]; [0183]; [0186]; [0329]; [0423]), which are either within or overlapping with the claimed range of 5-20mM, 10-15mM or 10mM recited in claims 46-48.
The polysorbate 80 disclosed by Bigal is at a concentration of 0.2 or 0.1 or 0.25 mg/ml (see para. [0151]; [0167]-[0169]; [0171]; [0174]-[0179]; [0181]; [0184]-[0186]), which are either within or overlapping with the claimed range of 0.03-0.07% or 0.05% recited in claims 42, 52-54.
The pH disclosed by Bigal includes pH 5-7,5, 5.5 or 6 which are either within or overlapping with the claimed range of 5.0-6.5, 5.5-6 or 5.8 recited in claims 55-57, 64 and 66.
The anti-CGRP antibody formulation disclosed by Bigal is suitable for subcutaneous injection in claim 58 (see para. [0015]-[0018]; [0031]; [0063]-[0066]; [0145]-[0150]; [0187]; [0193]-[0194-[0208]) and when stored in a prefilled syringe for 3 months at 25oC or 1 month at 40oC in claims 59-60.
The antibody disclosed by Bigal comprises the amino acid sequence of SEQ ID NO:62 and 63 for VL and VH, which are 100% identical to the VL (instant SEQ ID NO:1) and VH (instant SEQ ID NO:2) encompassed within the LC (instant SEQ ID NO:3) and HC (instant SEQ ID NO:4) of the instantly claimed anti-CGRP antibody recited in instant claims 42 and 64 (see the sequence alignment).
Thus, the anti-CGRP formulation disclosed by Bigal would also possess the claimed features and biological properties recited in amended independent claims 42 and 64 and claims 59-60 and 68.
While Bigal does not explicitly teach “a LC is given by SEQ ID NO:3 and a HC is given by SEQ ID NO: 4” recited in independent claims 42 and 64, Allan (US2011/0305711) teaches this limitation. Allan teaches an anti-CGRP antibody comprising a LC comprising the amino acid sequence of SEQ ID NO:29, which is 100% identical to instant SEQ ID NO:3 and a HC comprising the amino acid sequence of SEQ ID NO:34, which is 100% identical to instant SEQ ID NO:4 (see the sequence alignment below) and a pharmaceutical composition comprising the anti-CGRP antibody and a method of treating osteoarthritis pain (see para. [0022]-[0029]; claims 1-26)
While Bigal does not explicitly teach that the antibody is at a concentration sufficient to protect PS-80 from oxidation without addition of a separate antioxidant or wherein the formulation does not contain any additional antioxidant or that the dose ranges of the anti-CGRP antibody and the concentration ranges of a histidine buffer, NaCl, PS-80 (polysorbate 80) and the pH are exactly identical to the claimed ranges recited in independent claims 42 and 64, Kaisheva teaches these limitations and provides motivation and an expectation of success. Kaisheva teaches a stable liquid pharmaceutical formulation comprising a high concentration, e.g., greater than 50 mg/ml, of an antibody in 20-60 mM succinate buffer or 30-70 mM histidine buffer (pH from about pH 5.5 to about pH 6.5), a tonicity modifier, and about 0.01-0.1% polysorbate (see para. [0014]), which is without any additional antioxidant. Kaisheva teaches that stable liquid pharmaceutical formulations for IgG antibodies comprise an antibody at concentrations of greater than 50 mg/ml or 100mg/ml, a histidine buffer at about 30-70 mM, NaCl at 75-150 mM, polysorbate at about 0.01-0.1%; 0.01-0.05% or 0.02-0.04%, and a pH of about 5.5-6.5 or 6-6.5 (see abstract; claims 2-5, 7-8,10-11 and 13; paragraphs [0014]; [0021]; [0048]-[0052]; [0054]; Examples 1-2 and 5-11). Kaishev teaches that the liquid antibody formulation is stable at refrigerated temperature (2-8oC) for at least 1 year and preferably 2 years and is also stable at room temperature (23-27oC.) for at least six months and is suitable for subcutaneous injection (see para. [0015]; [0025]; claims 10-11).
A person of ordinary skill in the art would have recognized that selecting and applying the known anti-CGRP antibody having the LC and HC of SEQ ID NOs: 3-4 and the known formulation and the known concentrations for making a stable liquid pharmaceutical composition comprising an antibody, a histidine buffer, NaCl, polysorbate 80 and a pH at 5-6.5 or 5.5-6 without adding any additional antioxidant, and the known technique disclosed by Allan and Kaisheva to the anti-CGRP antibody formulation of Bigal would have yielded the predictable result of generating a stable anti-CGRP pharmaceutical formulation comprising: (a) 50-160 mg/mL of an anti-CGRP antibody having the SEQ ID NOs:3-4 for LC and HC; (b) 5-20 mM of histidine buffer; (c) 50-200 mM of NaCl; (d) 0.03-0.07% (w/v) of polysorbate-80 (PS-80); and (e) a pH of 5.0-6.5 or a stable anti-CGRP pharmaceutical formulation comprising: (a) 50-160 mg/mL of the same anti-CGRP antibody having the SEQ ID NOs:3-4 for LC and HC; (b) 10 mM of histidine buffer; (c) 150mMof NaCl; (d) 0.05% (w/v) of polysorbate-80 (PS-80); and (e) a pH from 5.5 to 6, and resulted in an improved product with a stable liquid pharmaceutical formulations for anti-CGRP antibodies without any additional antioxidant.
Using the known anti-CGRP antibody having the LC and HC of SEQ ID NOs: 3-4 and the known formulations and the known concentration of at least 50mg/ml or 50-160 mg/mL or 100mg/ML or 120mg/mL for an IgG antibody for making a stable liquid pharmaceutical composition comprising an antibody, a histidine buffer, NaCl, polysorbate 80 and a pH at 5-6.5 or 5.5-6 without adding any additional antioxidant in the anti-CGRP antibody formulation of Bigal would generate the claimed pharmaceutical formulation comprising the claimed concentrations of anti-CGRP antibody, histidine buffer, NaCl, PS-80 and pH without any additional antioxidant to stabilize the anti-CGRP and PS-80, and expand application of the anti-CGRP antibody formulation of Bigal to maintain a better shelf-life and stable liquid pharmaceutical formulations for the activity of the anti-CGRP antibodies. The concentrations for the anti-CGRP, histidine buffer, NaCl, PS-80 and pH in the stable liquid pharmaceutical formation of Bigal and Kaisheva are either identical to the claimed range or within the claimed range, the anti-CGRP formulation disclosed by Bigal and Kaisheva would also possess the claimed features and biological properties recited in independent claims 42 and 64 and dependent claims 59-63 and 68.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known anti-CGRP antibody having the LC and HC of SEQ ID NOs: 3-4 and the known formulation and the known concentrations for making a stable liquid pharmaceutical composition comprising an antibody, a histidine buffer, NaCl, polysorbate 80 and a pH at 5-6.5 or 5.5-6 without adding any additional antioxidant, and the known technique disclosed by Allan and Kaisheva to the anti-CGRP antibody formulation of Bigal, and yield the predictable result of a better stable anti-CGRP pharmaceutical formulation comprising: (a) 50-160 mg/mL of an anti-CGRP antibody having the SEQ ID NOs:3-4 for LC and HC; (b) 5-20 mM of histidine buffer; (c) 50-200 mM of NaCl; (d) 0.03-0.07% (w/v) of polysorbate-80 (PS-80); and (e) a pH of 5.0-6.5 or a better stable anti-CGRP pharmaceutical formulation comprising: (a) 50-160 mg/mL of the same anti-CGRP antibody having the SEQ ID NOs:3-4 for LC and HC; (b) 10 mM of histidine buffer; (c) 150mMof NaCl; (d) 0.05% (w/v) of polysorbate-80 (PS-80); and (e) a pH from 5.5 to 6.
Accordingly, the rejection of claims 42-60 and 64-68 under 35 U.S.C. 103 as being unpatentable over Bigal et al. (US2015/0266948) in view of Allan et al. (US2011/0305711) and Kaisheva (US2003/0138417) is maintained.
iv. In response to applicant's argument that the examiner has combined an excessive number of references, reliance on a large number of references in a rejection does not, without more, weigh against the obviousness of the claimed invention. See In re Gorman, 933 F.2d 982, 18 USPQ2d 1885 (Fed. Cir. 1991).
In this case, routine optimization of Bigal’s and Kaisheva’s dose ranges of anti-CGRP antibody, a histidine buffer, NaCl, polysorbate 80 and a pH would have led to the claimed range of 50-160 mg/ml for an anti-CGRP antibody; the claimed range of 5-20 mM or 10mM for histidine buffer, the claimed range of 50-200 mM or 150mM for NaCl, the claimed range of 0.03-0.07% (w/v) or 0.05%(w/v) for polysorbate-80 (PS-80) and the claimed range of 5.0-6.5 or 5.5-6 for a pH because Bigal teaches an anti-CGRP antibody at 150 mg/mL, 10-150mg/ml,…50mg/ml, 75mg/ml, 100mg/ml, 125mg/ml, 150mgml, 175mg/ml…1-150mg/ml 1-250mg/ml, a dose ranging from 100-2000 mg; histidine at a concentration of 1-20mM, 20mM, or 0.1-100mM; polysorbate 80 at a concentration of 0.2 or 0.1 or 0.25 mg/ml and pH at 5-7, 5, 5.5 or 6; and Kaisheva teaches an antibody at concentrations of greater than 50 mg/ml or 100mg/ml, a histidine buffer at about 30-70 mM, NaCl at 75-150 mM, polysorbate at about 0.01-0.1%; 0.01-0.05% or 0.02-0.04%, and a pH of about 5.5-6.5 or 6-6.5. The person of ordinary skill in the art would have found it obvious to optimize within the range taught by Bigal and Kaisheva because Bigal and Kaisheva teach that this entire range stabilizes liquid pharmaceutical formulations for antibodies or anti-CGRP antibodies, and also teaches how to optimize the dose ranges to generate stable liquid pharmaceutical formulations for IgG antibodies.
“[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.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)”; “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.” see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382; In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969); Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert.denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997). See MPEP § 2144.05.
Accordingly, the rejection of claims 42-60 and 64-68 under 35 U.S.C. 103 as being unpatentable over Bigal et al. (US2015/0266948) in view of Allan et al. (US2011/0305711) and Kaisheva (US2003/0138417) is maintained.
v. In response to Applicant’s arguments related to unexpected results, note that evidence of unexpected results must be weighed against evidence supporting prima facie obviousness in making a final determination of the obviousness of the claimed invention. In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978). See MPEP 716.02(c)-I. Any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. See: MPEP §716.02. In addition, “A greater than expected result is an evidentiary factor pertinent to the legal conclusion of obviousness ... of the claims at issue.” In re Corkill, 711 F.2d 1496, 226 USPQ 1005 (Fed. Cir. 1985). See MPEP 716.02(a)-I. Further, evidence of unexpected results is frequently in the form of a direct comparison of the claimed invention with the closest prior art which is commensurate in scope with the claims. See: e.g., In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980).
In this case, Applicants fails to provide evidence of side-by-side comparisons to demonstrate unexpected results as claimed. “Evidence of unexpected results must be weighed against evidence supporting prima facie obviousness in making a final determination of the obviousness of the claimed invention. In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978).” See MPEP 716.02(c)-I. Since Applicant fails to provide any evidence as discussed above to support any unexpected results as claimed, the claimed conjugate is obvious over the prior art, absent evidence to the contrary.
Accordingly, the rejection of claims 42-60 and 64-68 under 35 U.S.C. 103 as being unpatentable over Bigal et al. (US2015/0266948) in view of Allan et al. (US2011/0305711) and Kaisheva (US2003/0138417) is maintained.
Double Patenting
7. 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.
Claims 42-60 and 64-68 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of US11498959 in view of Bigal, Allan and Kaisheva. The rejection is maintained for the reasons of record and the reasons set forth below.
Claims 42-60 and 64-68 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of US9073991 or claims 1-7 of US9505838 in view of Bigal, Allan and Kaisheva. The rejection is maintained for the reasons of record and the reasons set forth below.
Claims 42-60 and 64-68 stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 50, 53, 76, 79-80 and 84-85 of copending Application No. 1755471 in view of Bigal, Allan and Kaisheva. The rejection is maintained for the reasons of record and the reasons set forth below.
Response to Arguments
On p. 12-13 of the response, Applicant argues that i) the combination of Bigal, Allan and Kaisheva does not render the instant claims obvious for the reasons set forth above. ii) claims 1-32 of US11498959 does not recite the limitations “prefilled syringe or pen” and the functional antioxidant limitations recited in independent claims 42 and 64. iii) the rejection over Application No. 17554713 is provisional.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §804, MPEP §2141, MPEP §2141-I, rationales identified by the Court in KSR (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, 82 USPQ2d 1385 (2007)), MPEP2141-II, the basic factual inquires of Graham v. John Deere Co.(Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966)),and MPEP §2141.01-2147.03, the cited references do render the claimed invention unpatentable because:
i. For the reasons above, the combination of Bigal, Allan and Kaisheva does teach the claimed prefilled syringe or pen recited in claims 42-60 and 64-68 for the reasons set forth above.
ii. Applicant cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In this case, the pharmaceutical formulation of the ‘959 patent contains the same ingredients: the same anti-CGRP comprising the same amino acid sequences for VL and VH or LC and HC at a range of 50-160mg/l, which meets the claimed range of 50-160mg/l and the same dose ranges for the histidine buffer (5-20mM), NaCl (50-200mM), PS-80 (0.03-0.07%(w/v) and a pH of 5-6.5. In addition, the claimed pharmaceutical formulation does not recite any additional antioxidants. The concentrations for the anti-CGRP, histidine buffer, NaCl, PS-80 and pH in the pharmaceutical formation of the ‘959 patent are either identical to the claimed range or within the claimed range, the anti-CGRP formulation disclosed by the ‘959 patent would also possess the claimed features and biological properties recited in independent claims 42 and 64 and dependent claims 59-60 and 68.
While The claims of the ‘959 patent do not recite the limitation “prefilled syringe or pen” or the dose ranges of the anti-CGRP antibody and the concentration ranges of a histidine buffer, NaCl, PS-80 (polysorbate 80) and the pH are exactly identical to the claimed ranges recited in independent claims 42 and 64, Bigal, Allan and Kaisheva teach these limitations and provide motivation and expectation of success for the reasons set forth above under the 103 rejection. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known prefilled syringe or pen comprising an anti-CGRP antibody having the LC and HC of SEQ ID NOs: 3-4 and the known formulation and the known concentrations for making a stable liquid pharmaceutical composition comprising an antibody, a histidine buffer, NaCl, polysorbate 80 and a pH at 5-6.5 or 5.5-6 and the known technique disclosed by Bigal, Allan and Kaisheva to the anti-CGRP antibody formulation of the 959 patent, and yield the predictable result of a better stable anti-CGRP pharmaceutical formulation comprising: (a) 50-160 mg/mL of an anti-CGRP antibody having the SEQ ID NOs:3-4 for LC and HC; (b) 5-20 mM of histidine buffer; (c) 50-200 mM of NaCl; (d) 0.03-0.07% (w/v) of polysorbate-80 (PS-80); and (e) a pH of 5.0-6.5 or a better stable anti-CGRP pharmaceutical formulation comprising: (a) 50-160 mg/mL of the same anti-CGRP antibody having the SEQ ID NOs:3-4 for LC and HC; (b) 10 mM of histidine buffer; (c) 150mMof NaCl; (d) 0.05% (w/v) of polysorbate-80 (PS-80); and (e) a pH from 5.5 to 6.
Accordingly, the rejection of claims 42-60 and 64-68 on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of US11498959 in view of Bigal, Allan and Kaisheva is maintained.
iii. The anti-CGRP antibody and the pharmaceutical composition recited in claims of the ‘991 patent or the ‘838 patent are identical to the anti-CGRP antibody, and the pharmaceutical formulation recited in instant claims.
While the claims of the ‘991 patent or the ‘838 patent do not recite the limitation “prefilled syringe or pen” or the dose ranges of the anti-CGRP antibody and the concentration ranges of a histidine buffer, NaCl, PS-80 (polysorbate 80) and the pH are exactly identical to the claimed ranges recited in independent claims 42 and 64, Bigal, Allan and Kaisheva teach these limitations and provide motivation and expectation of success for the reasons set forth above under the 103 rejection. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known prefilled syringe or pen comprising an anti-CGRP antibody having the LC and HC of SEQ ID NOs: 3-4 and the known formulation and the known concentrations for making a stable liquid pharmaceutical composition comprising an antibody, a histidine buffer, NaCl, polysorbate 80 and a pH at 5-6.5 or 5.5-6 and the known technique disclosed by Bigal, Allan and Kaisheva to the anti-CGRP antibody formulation of the ‘991 patent or ‘838 patent, and yield the predictable result of a better stable anti-CGRP pharmaceutical formulation comprising: (a) 50-160 mg/mL of an anti-CGRP antibody having the SEQ ID NOs:3-4 for LC and HC; (b) 5-20 mM of histidine buffer; (c) 50-200 mM of NaCl; (d) 0.03-0.07% (w/v) of polysorbate-80 (PS-80); and (e) a pH of 5.0-6.5 or a better stable anti-CGRP pharmaceutical formulation comprising: (a) 50-160 mg/mL of the same anti-CGRP antibody having the SEQ ID NOs:3-4 for LC and HC; (b) 10 mM of histidine buffer; (c) 150mMof NaCl; (d) 0.05% (w/v) of polysorbate-80 (PS-80); and (e) a pH from 5.5 to 6.
Accordingly, the rejection of claims 42-60 and 64-68 on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of US9073991 or claims 1-7 of US9505838 in view of Bigal, Allan and Kaisheva is maintained.
iv. The anti-CGRP antibody and the pharmaceutical composition recited in claims of the ‘713 Application are identical to the anti-CGRP antibody, and the pharmaceutical formulation recited in instant claims.
While the claims of the ‘713 Application do not recite the limitation “prefilled syringe or pen” or the dose ranges of the anti-CGRP antibody and the concentration ranges of a histidine buffer, NaCl, PS-80 (polysorbate 80) and the pH are exactly identical to the claimed ranges recited in independent claims 42 and 64, Bigal, Allan and Kaisheva teach these limitations and provide motivation and expectation of success for the reasons set forth above under the 103 rejection. Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known prefilled syringe or pen comprising an anti-CGRP antibody having the LC and HC of SEQ ID NOs: 3-4 and the known formulation and the known concentrations for making a stable liquid pharmaceutical composition comprising an antibody, a histidine buffer, NaCl, polysorbate 80 and a pH at 5-6.5 or 5.5-6 and the known technique disclosed by Bigal, Allan and Kaisheva to the anti-CGRP antibody formulation of the ‘713 Application, and yield the predictable result of a better stable anti-CGRP pharmaceutical formulation comprising: (a) 50-160 mg/mL of an anti-CGRP antibody having the SEQ ID NOs:3-4 for LC and HC; (b) 5-20 mM of histidine buffer; (c) 50-200 mM of NaCl; (d) 0.03-0.07% (w/v) of polysorbate-80 (PS-80); and (e) a pH of 5.0-6.5 or a better stable anti-CGRP pharmaceutical formulation comprising: (a) 50-160 mg/mL of the same anti-CGRP antibody having the SEQ ID NOs:3-4 for LC and HC; (b) 10 mM of histidine buffer; (c) 150mMof NaCl; (d) 0.05% (w/v) of polysorbate-80 (PS-80); and (e) a pH from 5.5 to 6.
Accordingly, the provisional rejection of Claims 42-60 and 64-68 on the ground of nonstatutory double patenting as being unpatentable over claims 50, 53, 76, 79-80 and 84-85 of copending Application No. 17554713 is maintained of record until a terminal disclaimer is filed.
New Grounds of Rejection Necessitated by the Amendment
The following rejections are new grounds of rejections necessitated by the amendment filed on June 11, 2026 and July 15, 2026.
Claim Rejections - 35 USC § 112
8. 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.
Claims 42-60 and 64-68 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claims 42-60 and 64-68 are indefinite because:
i. Claim 42 or 64 recites the limitation "the addition of a separate antioxidant " in line 12 of claim 42 or in line 11 of claim 64. There is insufficient antecedent basis for this limitation in the claim.
ii. The rest of claims are indefinite as depending from an indefinite claim.
Claim Rejections - 35 USC § 112
9. The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), fourth paragraph:
Subject to the [fifth paragraph of 35 U.S.C. 112 (pre-AIA )], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 65 is rejected 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. Claim 65 recites “wherein the formulation comprises 100mg/mL or 120mg/mL…”. and also depends from claim 64 that recites “100mg/mL or 120 mg/mL…). Thus, Claim 65 fails to further limit the subject matter of the claim upon which it depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112
10. The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
Claims 42-60 and 64-68 are ejected 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(s) 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Claims 42-60 as amended are directed to a prefilled syringe or pen comprising a pharmaceutical formulation comprising: (a) 50-160 mg/mL of an anti-CGRP antibody; (b) 5-20 mM of histidine buffer;(c) 50-200 mM of NaCl; (d) 0.03-0.07% (w/v) of polysorbate-80 (PS-80); and (e) a pH of 5.0-6.5, and wherein the anti-CGRP antibody comprises two light chains (LCs) and two heavy chains (HCs), the amino acid sequence of each LC given by SEQ ID NO: 3 and the amino acid sequence of each HC given by SEQ ID NO: 4; wherein the anti-CGRP antibody is present at a concentration sufficient to protect the PS-80 from oxidation without the addition of a separate antioxidant, and wherein the pharmaceutical composition does not comprise any additional antioxidants.
Claims 64-68 as amended are drawn to a prefilled syringe or pen comprising a pharmaceutical formulation as set forth above but comprising: (a) 100 or 120 mg/mL of the same anti-CGRP antibody;(b) 10 mM of histidine buffer; (c) 150mMof NaCl; (d) 0.05% (w/v) of polysorbate-80 (PS-80); and (e) a pH from 5.5 to 6.
The instant claims now recite new limitations “wherein the anti-CGRP antibody is present at a concentration sufficient to protect the PS-80 from oxidation without the addition of a separate antioxidant, and wherein the pharmaceutical composition does not comprise any additional antioxidants”, which were not clearly disclosed in the specification and claims as filed, and now change the scope of the instant disclosure as filed. Such limitations recited in the present claims, which did not appear in the specification or original claims, as filed, introduce new concepts and violate the description requirement of the first paragraph of 35 U.S.C. 112.
The specification fails to disclose the new limitations “wherein the anti-CGRP antibody is present at a concentration sufficient to protect the PS-80 from oxidation without the addition of a separate antioxidant, and wherein the pharmaceutical composition does not comprise any additional antioxidants”.
The specification only discloses “an anti-CGRP antibody at a concentration of about 40 mg/mL-160 mg/mL, about 50mg/mL-150mg/mL or about 100mg/mL-160mg/mL, about 50mg/mL-100mg/mL; histidine buffer at a concentration of about 5 mM-20 mM or about 10mM; sodium chloride (NaCl) at a concentration of about 50 mM- 200 mM or about 150mM; PS-80 at a concentration of about 0.03% (w/v)-0.07% (w/v) or about 0.05% (w/v); and a pH at about 5.0- 6.5 or about 5.8 or ”(see para. [0006]-[0016] of the published specification). Accordingly, in the absence of sufficient recitation for the new limitations “wherein the anti-CGRP antibody is present at a concentration sufficient to protect the PS-80 from oxidation without the addition of a separate antioxidant, and wherein the pharmaceutical composition does not comprise any additional antioxidants”, the specification does not provide adequate written description to support the new limitations recited in independent claims 42 and 64. Support is not found for the new limitations ““wherein the anti-CGRP antibody is present at a concentration sufficient to protect the PS-80 from oxidation without the addition of a separate antioxidant, and wherein the pharmaceutical composition does not comprise any additional antioxidants” as disclosed in the original specification and thus the recitations constitute new matter absent evidence for their support. Applicant is required to cancel the new matter in the reply to this office action. Alternatively, Applicant is invited to clearly point out the written support for the instant limitations.
Conclusion
11. NO CLAIM IS ALLOWED.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached Monday-Thursday, 7:00am-5:00pm EST.
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Chang-Yu Wang
September 5, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675
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