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 .
Status of the Claims
Claims 14-24, 26, 28, and 31-37 are pending. Claims 14-24, 26, 28, and 31-37 are rejected.
Information Disclosure Statement
The Information Disclosure Statement (IDS) submitted on 5/4/2026 was considered by the Examiner.
Response to Arguments
**Examiner notes that no amendments were made on the 5/4/2026 claim set.
Applicant's arguments filed 5/4/2026 have been fully considered but they are not persuasive. Applicant’s arguments will be addressed here.
On p. 5 of the response, Applicant argues that Examiner used hindsight to select the administration of a gepant specifically to identify, select, and then treat those migraine sufferers who do not exhibit signs of interictal allodynia and/or hyperalgesia. Examiner respectfully disagrees and reiterates the rejection below. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
On p. 5-6 of the response, Applicant argues surprising results of gepants on central sensitization depending on pain signals that arrive from the meninges (refers to Example 3). Examiner respectfully disagrees that this overcomes the rejections below. Consequently, “Mere recognition of latent properties in the prior art does not render nonobvious an otherwise known invention. In re Wiseman, 596 F.2d 1019, 201 USPQ 658 (CCPA 1979)”. Also, “The fact that appellant has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious." Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985)”. See MPEP 2145(II).
On p. 6-7 of the response, Applicant argues that the provisional obvious double patenting rejection was premature. Examiner respectfully disagrees and maintains the rejection, as described below.
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.
Claim(s) 14, 15, 16, 17, 19, 20, 21, 22, 23, 24, 26, 28, 32, 33, 34, 35, 36 and 37 is/are rejected under 35 U.S.C. 103 as being unpatentable over Blumenfeld et al. (WO2020008402), in view of Lipton et al. (American Neurological Association, 2008: 63, 148-158).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Blumenfeld teaches the following in para. [0002]: “Migraine is a common neurological disorder that affects up to 16% of the adult population in Western countries. It is characterized by attacks, often of disabling headache, which can be associated with sensory, visual, or language (aura), associated symptoms such as nausea and/or vomiting, phonophobia, and photophobia, as well as dizziness and cognitive symptoms”.
Claim 3 of Blumenfeld recites the following: “A method for treating, preventing, alleviating or reducing the frequency of occurrence of migraine or a symptom of migraine in a patient in need thereof, comprising administering to the patient an antagonist of calcitonin gene-related peptide (CGRP-antagonist), wherein said patient is concurrently undergoing treatment with a clostridial derivative”. Claim 11 of Blumenfeld teaches that the CGRP antagonist may be Rimegepant (also a gepant). Claims 95 and 96 of Blumenfeld teach that the method may be for when the migraine is either a chronic or episodic migraine.
Blumenfeld does not teach determining or having determined whether a treated subject exhibits allodynia in the ictal (active) or interictal (interval between two migraine attacks) phase of a migraine.
Lipton’s objective was to develop and validate a questionnaire for assessing cutaneous allodynia (CA) and to estimate the prevalence of cutaneous allodynia in the migraine population (see objective, p 148). “CA is usually assessed by quantitative sensory testing (QST)” (see p. 148, left column, second para.). Lipton’s questionnaire successfully determined the presence of allodynia among migraineurs was 63.2% and severe CA occurred in 20.4% of migraineurs (see results, p. 148). Additionally, Lipton teaches: “As a marker of central sensitization, allodynia has been proposed as a risk factor for progression to chronic migraine. Therefore, CA has significant implications for our understanding of the pathophysiology of migraine attacks, for the implementation of treatment, and for assessing prognosis” (see p. 148, left column).
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The prior art does not have a single embodiment of both determining or having determined the present of allodynia during the ictal or interictal phase of a migraine AND administering rimegepant to the subject that does not exhibit signs of allodynia during the interictal phase (interval between two migraine attacks) of the migraine. Additional dependent limitations will be addressed below.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
Regarding instant claims 14-17, 19-23 and 32-34, it would have been obvious to a skilled artisan to determine the presence of (cutaneous) allodynia during an active/acute (ictal) migraine phase and administer Rimegepant during various phases of the migraine and/or when the subject is migraine-free. Allodynia was known to be an important symptom for understanding migraine attacks and the way treatment is administered. Blumenfeld’s “preventing” by administering Rimegepant embraces the instant claims (particularly instant claim 22), for both chronic and episodic sufferers. By administering Rimegepant while the patient is migraine-free, a PHOSITA would reasonably expect that this would successfully prevent the occurrence of the migraine and its symptoms. Blumenfeld also teaches that the subject is undergoing treatment with a clostridial derivative, wherein the instant claims transitional phrase of comprising does not preclude other treatment elements.
Additionally, both questionnaires and QST to determine the presence or lack thereof of allodynia were common place with migraine suffers, prior to the effective filing date of the claimed invention. A skilled artisan would have had a reasonable expectation of success in the use of either QST or a questionnaire to explore the presence or absence of allodynia, a common symptom for migraine sufferers (63.2% of them according to Lipton).
Particularly regarding instant claims 32-34, the prior art embraces treating migraines, wherein it would have been obvious to a skilled artisan to provide a gepant once the active/acute (ictal phase) of the migraine commences. The timing of administration of the gepant would have been optimized as a result of routine experimentation. A PHOSITA would have been motivated to treat an acute migraine within 60 minutes to 3 hour time frame in an effort to reduce symptoms in the patient with a reasonable expectation of success.
Regarding instant claims 24 and 35-36, it would have been obvious to a PHOSITA to determine whether a subject experiences allodynia or not during an interictal phase of a migraine and to the administer the gepant to reduce migraine frequency, particularly Rimegepant. Allodynia was known to be an important symptom for understanding migraine attacks and the way treatment is administered. A skilled artisan would have been motivated to obtain data regarding allodynia during various phases of a migraine sufferer’s journey in an effort to prevent and/or treat the migraine, by administering a gepant such as Rimegepant, during various migraine phases. In doing so, a skilled artisan would have had a reasonable expectation of success of mitigating and/or preventing the symptoms (including allodynia) of all phases of a migraine and reducing migraine frequency overall.
Regarding instant claims 26 and 37, it would have been obvious to a PHOSITA to determine whether a subject experiences allodynia or not during an interictal phase of a migraine and to the administer the gepant (Rimegepant). Allodynia was known to be an important symptom for understanding migraine attacks and the way treatment is administered. A skilled artisan would have been motivated to obtain data regarding allodynia during various phases of a migraine sufferer’s journey in an effort to treat the migraine, by administering a gepant such as Rimegepant, during various phases of the migraine. In doing so, a skilled artisan would have had a reasonable expectation of success of treating the symptoms (including allodynia) of all phases of a migraine. Regarding instant claim 28, it would have been obvious to a PHOSITA to administer the gepant within 3 hours of the start of the ictal phase of the migraine as a result of routine optimization. A skilled artisan would have been motivated to explore the administration of the gepant to treat migraine over various time periods with a reasonable expectation of success in reducing or eliminating patient symptoms.
Claim(s) 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Blumenfeld et al. (WO2020008402), in view of Lipton et al. (American Neurological Association, 2008: 63, 148-158), as applied to claims 14, 15, 16, 17, 19, 20, 21, 22, 23, 24, 26, 28, 32, 33, 34, 35, 36 and 37 above, and further in view of Wasner et al. (Clinical Neurophysiology 119, 2008, 2389-2395).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Neither Blumenfeld nor Lipton disclose information regarding heat pain threshold levels. Wasner performed a study on determinants of thermal pain thresholds in normal subjects (See title). See Table 1 on p. 2391:
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. In Table 1, shown here, the median heat pain threshold for two different protocols (Protocol A and Protocol B) was 42.9 °C and 43.8 °C.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
The prior art does not have a single embodiment of both determining or having determined the present of allodynia during the ictal phase of a migraine AND administering rimegepant to the subject that does not exhibit signs of allodynia during the interictal phase (interval between two migraine attacks) of the migraine, wherein during the interictal phase of the migraine the subject has a heat pain threshold of above 41 °C.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
Regarding instant claim 18, a skilled artisan would reasonably expect a subject in the interictal phase (between migraine attacks) to have a normal heat pain threshold. The prior art experimentally determined that the normal heat pain threshold is above 41 °C (42.9 °C and 43.8 °C). This data further reinforces that it would have been obvious to treat a subject during various phases of migraine in an effort to prevent or treat the ictal (active) phase of migraine and negative symptoms at any time, improving a patient’s quality of life.
Claim(s) 18 and 31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Blumenfeld et al. (WO2020008402), in view of Lipton et al. (American Neurological Association, 2008: 63, 148-158), as applied to claims 14, 15, 16, 17, 19, 20, 21, 22, 23, 24, 26, 28, 32, 33, 34, 35, 36 and 37 above, and further in view of Burstein (US11718664).
Determining the scope and contents of the prior art. (See MPEP § 2141.01)
Neither Blumenfeld nor Lipton disclose information regarding heat pain threshold levels.
Burstein teaches migraine treatment wherein claim 1 recites the following:
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. Additionally, Burstein claim 5, which depends from claim 1 recites the following:
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.
Ascertainment of the differences between the prior art and the claims. (See MPEP § 2141.02)
There is not a single embodiment in the art of specifically administering a gepant, such as Rimegepant, wherein the subject was determined during the interictal phase of the migraine to have a heat pain threshold of above 41 °C or to have a mechanical pain threshold of above 30g for skin indentation with calibrated von Frey hairs.
Finding of prima facie obviousness --- rationale and motivation (See MPEP § 2142-2143)
Regarding instant claims 18 and 31, it would have been obvious to a skilled artisan to treat a migraine sufferer during various phases of the migraine who either have one or both of: during the interictal phase of the migraine to have a heat pain threshold of above 41 °C or to have a mechanical pain threshold of above 30g for skin indentation with calibrated von Frey hairs. These were known indicators of migraine sufferers prior to the effective filing date of the claimed invention. Additionally, Blumenfeld teaches that the CGRP antagonist may be Rimegepant (also a gepant), which is additionally embraced by Burstein. Consequently, a skilled artisan would have been motivated to treat a subject with the parameters above to reduce/prevent/treat migraine symptoms overall and improve a patient’s quality of life.
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.
Claims 14-24, 26, 28, and 31-37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14, 17, 19, 25-27, and 37 of copending Application No. 18294553 in view of Blumenfeld et al. (WO2020008402), in view of Lipton et al. (American Neurological Association, 2008: 63, 148-158), and further in view of Burstein (US11718664).
Claim 1 of the co-pending application recites the following:
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Claims 25 and 26 of the copending application recite the following:
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Blumenfeld teaches the following in para. [0002]: “Migraine is a common neurological disorder that affects up to 16% of the adult population in Western countries. It is characterized by attacks, often of disabling headache, which can be associated with sensory, visual, or language (aura), associated symptoms such as nausea and/or vomiting, phonophobia, and photophobia, as well as dizziness and cognitive symptoms”.
Claim 3 of Blumenfeld recites the following: “A method for treating, preventing, alleviating or reducing the frequency of occurrence of migraine or a symptom of migraine in a patient in need thereof, comprising administering to the patient an antagonist of calcitonin gene-related peptide (CGRP-antagonist), wherein said patient is concurrently undergoing treatment with a clostridial derivative”. Claim 11 of Blumenfeld teaches that the CGRP antagonist may be Rimegepant (also a gepant). Claims 95 and 96 of Blumenfeld teach that the method may be for when the migraine is either a chronic or episodic migraine.
Blumenfeld does not teach determining or having determined whether a treated subject exhibits allodynia in the ictal (active) or interictal (interval between two migraine attacks) phase of a migraine.
Lipton’s objective was to develop and validate a questionnaire for assessing cutaneous allodynia (CA) and to estimate the prevalence of cutaneous allodynia in the migraine population (see objective, p 148). “CA is usually assessed by quantitative sensory testing (QST)” (see p. 148, left column, second para.). Lipton’s questionnaire successfully determined the presence of allodynia among migraineurs was 63.2% and severe CA occurred in 20.4% of migraineurs (see results, p. 148). Additionally, Lipton teaches: “As a marker of central sensitization, allodynia has been proposed as a risk factor for progression to chronic migraine. Therefore, CA has significant implications for our understanding of the pathophysiology of migraine attacks, for the implementation of treatment, and for assessing prognosis” (see p. 148, left column).
Neither Blumenfeld nor Lipton disclose information regarding heat pain threshold levels.
Burstein teaches migraine treatment wherein claim 1 recites the following:
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. Additionally, Burstein claim 5, which depends from claim 1 recites the following:
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.
Regarding instant claims 14-17, 19-23 and 32-34, it would have been obvious to a skilled artisan to determine the presence of (cutaneous) allodynia during an active/acute (ictal) migraine phase and administer Rimegepant during various phases of the migraine and/or when the subject is migraine-free. Allodynia was known to be an important symptom for understanding migraine attacks and the way treatment is administered. Blumenfeld’s “preventing” by administering Rimegepant embraces the instant claims (particularly instant claim 22), for both chronic and episodic sufferers. By administering Rimegepant while the patient is migraine-free, a PHOSITA would reasonably expect that this would successfully prevent the occurrence of the migraine and its symptoms. Blumenfeld also teaches that the subject is undergoing treatment with a clostridial derivative, wherein the instant claims transitional phrase of comprising does not preclude other treatment elements.
Additionally, both questionnaires and QST to determine the presence or lack thereof of allodynia were common place with migraine suffers, prior to the effective filing date of the claimed invention. A skilled artisan would have had a reasonable expectation of success in the use of either QST or a questionnaire to explore the presence or absence of allodynia, a common symptom for migraine sufferers (63.2% of them according to Lipton).
Particularly regarding instant claims 32-34, the prior art embraces treating migraines, wherein it would have been obvious to a skilled artisan to provide a gepant once the active/acute (ictal phase) of the migraine commences. The timing of administration of the gepant would have been optimized as a result of routine experimentation. A PHOSITA would have been motivated to treat an acute migraine within 60 minutes to 3 hour time frame in an effort to reduce symptoms in the patient with a reasonable expectation of success.
Regarding instant claims 24 and 35-36, it would have been obvious to a PHOSITA to determine whether a subject experiences allodynia or not during an interictal phase of a migraine and to the administer the gepant to reduce migraine frequency, particularly Rimegepant. Allodynia was known to be an important symptom for understanding migraine attacks and the way treatment is administered. A skilled artisan would have been motivated to obtain data regarding allodynia during various phases of a migraine sufferer’s journey in an effort to prevent and/or treat the migraine, by administering a gepant such as Rimegepant, during various migraine phases. In doing so, a skilled artisan would have had a reasonable expectation of success of mitigating and/or preventing the symptoms (including allodynia) of all phases of a migraine and reducing migraine frequency overall.
Regarding instant claims 26 and 37, it would have been obvious to a PHOSITA to determine whether a subject experiences allodynia or not during an interictal phase of a migraine and to the administer the gepant (Rimegepant). Allodynia was known to be an important symptom for understanding migraine attacks and the way treatment is administered. A skilled artisan would have been motivated to obtain data regarding allodynia during various phases of a migraine sufferer’s journey in an effort to treat the migraine, by administering a gepant such as Rimegepant, during various phases of the migraine. In doing so, a skilled artisan would have had a reasonable expectation of success of treating the symptoms (including allodynia) of all phases of a migraine. Regarding instant claim 28, it would have been obvious to a PHOSITA to administer the gepant within 3 hours of the start of the ictal phase of the migraine as a result of routine optimization. A skilled artisan would have been motivated to explore the administration of the gepant to treat migraine over various time periods with a reasonable expectation of success in reducing or eliminating patient symptoms.
Regarding instant claims 18 and 31, it would have been obvious to a skilled artisan to treat a migraine sufferer during various phases of the migraine who either have one or both of: during the interictal phase of the migraine to have a heat pain threshold of above 41 °C or to have a mechanical pain threshold of above 30g for skin indentation with calibrated von Frey hairs. These were known indicators of migraine sufferers prior to the effective filing date of the claimed invention. Additionally, Blumenfeld teaches that the CGRP antagonist may be Rimegepant (also a gepant), which is additionally embraced by Burstein. Consequently, a skilled artisan would have been motivated to treat a subject with the parameters above to reduce/prevent/treat migraine symptoms overall and improve a patient’s quality of life.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Applicant’s amendments necessitated the new ground(s) of rejection presented in this Office Action. Accordingly, THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MEGHAN C HEASLEY whose telephone number is (571)270-0785. The examiner can normally be reached Monday - Friday 8:30-4:30 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joseph McKane can be reached on 571-272-0699. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MEGHAN C HEASLEY/Examiner, Art Unit 1626
/KAMAL A SAEED/Primary Examiner, Art Unit 1626
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