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 .1
Status of claims
Claims 1-28 and 30 are pending. Note that missing claim 29 must be addressed by amendment by Applicant.
Information Disclosure Statement
At this time, an Information Disclosure Statement has not been filed.
Claim Objections
Claim 30 is objected to because of the following informalities: claim 30 follows claim 28 without an intervening claim 29. It must be renumbered claim 29 by Applicant, as the claims as filed did have a claim 29. Appropriate correction is required.
Claim Interpretation
Claim 1 is directed to: a method of reducing the frequency of migraine attacks in a subject who has frequent migraine headaches with or without aura, comprising:
administering a pharmaceutical composition comprising dihydroergotamine (DHE) or salt
thereof via a respiratory tract of the subject on a repeat dose schedule, wherein the repeat dose schedule is a chronic intermittent schedule comprising
intermittent administration of multiple doses, wherein each dose is administered while the subject is experiencing a particular migraine headache and the repeat dose schedule comprises administration of
two or more doses within a 28-day initial administration period and
no more than 2 doses within a 24-hour period and 3 doses in a 7-day period, wherein the repeat dose schedule lasts at least one month.
Claim 1 recites the transition phrase “comprising” with regard to “the repeat dose schedule is a chronic intermittent schedule comprising.” While the chronic intermittent schedule is said to be “intermittent administration of multiple doses, wherein each dose is administered while the subject is experiencing a particular migraine headache. The term “comprising” allows for administration of additional DHE outside the scope of the doses scheduled intermittently (while the subject is experiencing a particular migraine) and repeatedly (2 or more doses with 28 day initial admin and no more than 2 doses with 24 hrs/3 doses/ 7 days) as recited. Comprising opens the claimed method for additional doses of DHE outside the defined intermittent and repeat schedules.
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.
Claims 1-6, 8-28 and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Silberstein et al. “Dihydroergotamine (DHE) – Then and Now: A Narrative Review,” Headache: The Journal of Head and Face Pain Volume 60, Issue 1 Pages: 40-57 First Published: 17 November 2019 (Silberstein 2019) as evidenced by Cady 2015 Excerpt from Headache and Migraine Biology and Management, 2015 and Aurora et al. A randomized, double blind, placebo-controlled study of MAP0004 in adult patients with migraine. Headache. 2009;49:826-837.2 Silberstein 2019 was cited on Applicant’s IDS (submitted in the parent case (17148154) of this Continuation Application) submitted on or about Jan 21 2021. Cady 2015 was listed on a PTO-892 form in the parent application, 17148154. Aurora is listed on the PTO-892 form.
Claim 1 is directed to:
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Claim 1 has support in the specification as follows:
intranasally administering a pharmaceutical composition comprising dihydroergotamine (DHE) mesylate on a repeat dose schedule, wherein each intranasal administration is delivered by a manually actuated, propellant-driven, metered-dose administration device, and wherein the schedule is a chronic intermittent schedule in which each of the repeated administrations is performed while the subject is experiencing a migraine headache, is effective both to treat acute symptoms, and over repeated dosing, is also effective in reducing the frequency of migraine attacks. As described in detail in Example 3, administration provided acute relief pain - including pain relief at 2 hours, and increased pain freedom and relief of the most bothersome symptom at 2 hours - and upon repeated PRN dosing, reduced migraine attack frequency. See paragraph 6.
The working example of the specification discloses use of the POD® Device, which as further discussed below, is the same POD® handheld, manually actuated propellant-driven metered dose delivery system used to administer Migranal DHE as taught by Silberstein 2019.
The limitations of claim 1 are taught by Silberstein 2019 (as evidenced by Cady) as follows:
Claim 1’s subject in need: subject who has frequent migraine headaches with or without aura comprising
administering a pharmaceutical composition comprising dihydroergotamine (DHE) or salt
Silberstein 2019 discloses treatment of migraine subject in general with headaches, see abstract and sections “MIGRAINE” and “TREATMENT OF MIGRAINE.” Page 42 columns 1-2. See also Silberstein 2019 disclosing use of DHE for migraine with frequent recurrence, see page 52, first column, last paragraph. Silberstein 2019 discloses Migranal DHE (aka INP104, delivered by Precision Olfactory Delivery (POD)® device, where propellant and DHE are kept separate until delivery, delivering a larger fraction of DHE to the upper nasal region, see Fig. 3) over traditional pump systems. See page 47, column 2, section INP104; Figs 2-3, pages 48-49, reproduced below.
Thus Silberstein 2019 discloses the advantages of INP104 and the POD delivery device over traditional pump devices, as per the claimed method of claim 1.
thereof via a respiratory tract of the subject on a repeat dose schedule
(where the specification at paragraph 6 defines a repeat schedule limitation as schedule per Example 3, i.e., administration provided acute relief pain - including pain relief at 2 hours, and increased pain freedom and relief of the most bothersome symptom at 2 hours).
Regarding a frequent and repeat dose schedule of DHE, Silberstein 2019 discloses DHE is used to treat migraine patients in the presence of allodynia or frequent recurrence, see page 52, column 1, last paragraph.
POD® delivery of DHE from 1-4 hours meets the repeat dose schedule limitation that requires relief of symptoms at 2 hours.
Silberstein 2019 discloses a repeat schedule, where it notes that DHE administered via the POD® delivery system (INP104) achieves a pharmacokinetic profile similar to intravenous (IV) DHE, where Silberstein 2019 discloses intermittent delivery of DHE in a clinical setting, see page 44, columns 1-2.
Silberstein 2019 discloses that POD delivery of DHE into a subject achieved the ideal pharmacokinetic plasma concentration profile of intravenous delivery (IV) of DHE over time, vs traditional pump delivery of DHE, see Figure 5, noting the higher concentrations of POD delivery of DHE 1.45 mg at time periods from 1-4 hours vs . traditional DHE (Migranal 2.0 mg).
Comprising intermittent administration of multiple doses, where each dose is administered when subject experiencing a particular migraine headache
Silberstein 2019 notes that INP104 DHE administered by POD® device achieves a pharmacokinetic profile that mimics that of intravenous IV DHE, see Figure 5 and page 47, column 2.
Silberstein 2019 suggests how IV DHE is used in a clinical for both intermittent administration of multiple doses when a subject is experiencing a migraine attack in a clinical setting, see page 44, columns 1-2.
Therefore, a person having ordinary skill in the art (PHOSITA) would have a rationale to look towards treating intermittent administration of DHE via INP104 DHE as it teaches a PK profile similar to IV administration where IV administration is noted to be used for intermittent and repeat dosing of DHE per Silberstein.
the repeat dose schedule comprises administration of
(i) two or more doses within a 28 day initial administration period and
(ii) no more than 2 doses within a 24-hour period and 3 doses in a 7-day period.
Silberstein 2019 suggests the repeat dose limitation of two or more doses in a 28 day period and no more than 2 doses within 24 hour and 3 doses in a 7 day period, where it notes that INP104 matching the plasma concentration profile of IV DHE within 20 minutes and up to 48 hours, see page 48, column 1. See also Figure 5 of Silberstein 2019.
Silberstein 2019 notes that systemic DHE has a rapid onset and sustained effects of up to 48 hours, see page 43, column 2, last paragraph. Silberstein 2019 discloses DHE exerts activity after migraine onset, from an early 2 hours to a late 8 hours after onset.
Further, as evidenced by Cady 2015 notes that DHE has a half-life of 9 hours, see Cady middle of excerpt. While not explicitly reciting the dose limitations of claim 1, it would be routine for a PHOSITA to adjust the dosing of DHE based on its known onset and sustained effects in a subject as known in the art.
wherein the repeat dose schedule lasts at least one month.
Silberstein 2019 teaches a Phase 2 trial, where as evidenced by Aurora 2009, teaches the treated subjects suffered from acute migraines for over 12 months. See page 45, column 2 bridging to page 46, column 1. See Aurora 2009, abstract.
Figures 2, 3 and 5 from Silberstein 2019 are reproduced below for reference purposes:
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Although Silberstein 2019 teaches claim 1 with reducing the frequency of migraine attacks in a subject in need regard to intranasal administration of DHE, it does not explicitly recite the claim limitations of claim 1 with regard to repeat dose schedule and the repeat schedule and the repeat schedule lasts at least one month. However as noted above in the claim chart and accompanying Figures from Silberstein 2019 and as evidenced by Cady, each of the elements of claim 1 are obvious because the prior art routinely discloses reducing migraine attack frequency with intranasal DHE administered via the POD® device to routinely administer DHE according to the claimed repeat dose schedule. For example, see the teachings of Silberstein 2019 starting at page 47 and referenced via Figures 1, 3 and 5 above, as evidenced by Cady.
With regard to the limitation where the repeat schedule lasts at least one month, Silberstein 2019 teaches a randomized double-blind placebo-controlled Phase 2 study in acute migraine patients with MAP004 DHE. See page 45, column 2 bridging to page 46, column 1. This Phase 2 study, referenced by Silberstein 2019 is detailed by Aurora 2009, noting it was conducted at 9 headache centers in the U.S., in adult men and women with a documented history of acute migraine for at least 12 months. See abstract Aurora. A PHOSITA would routinely treat a subject with a repeat schedule of at least one month, where such subjects have a history of migraines for at least 12 months.
Prior to the filing of the present patent application, it would have been prima facie obvious to a PHOSITA following the teachings of Silberstein 2019 for reducing the frequency of migraine attacks in a subject in need regard to intranasal administration of DHE modified by the teachings of Silberstein 2019 itself with regard to the claim chart and Figures above, as evidenced by Cady, modified, in order to repeat dose and repeat schedule to routinely disclose reducing migraine attack frequency according to the claimed repeat dose schedule.
The PHOSITA would have had a reasonable expectation of success because Silberstein 2019 teaches DHE is administered intranasally by the POD® device (relied upon by the Applicant’s disclosure) by using the routine Migranal DHE formulation and by routinely arrive at the claimed repeat schedule based off the teachings of Silberstein 2019, as evidenced by Cady, where the half-life and pharmacokinetics of DHE are known to predict the claimed dose schedule. The rationale being a combination of prior art elements according to known methods (the adjustment of known methods to treat migraine with DHE) to yield predictable results, the claimed method.
Claims 2-3 and 6 require the limitation of intranasal administration of a liquid pharmaceutical composition of DHE by a manually actuated, propellant driven, metered dose administration device. As noted above, Silberstein 2019 discloses the POD® delivery device to administer the liquid Migranal DHE formulation as required by the claims, see Silberstein 2019 starting at page 47, column 2.
Regarding claim 4, Silberstein 2019 teaches pulmonary administration of DHE. See page 46, column 1. See also page 46, column 2, last paragraph.
Regarding claim 5 and the limitation of the repeat dose schedule of a first and second dose, Silberstein 2019 suggest a first and second dose where INP104 DHE is used to administer a single 1.45 mg dose, see page 47, column 2, where Cady evidences a half-life of 9 hours for DHE, thus requiring a second dose to any first dose as DHE is metabolized in the subject.
Claims 8-9, that require the limitation of hydroxy fluoroalkane (HFA) propellant, Silberstein 2019 discloses the use of the POD® intranasal delivery device that use HFA propellant, see page 47, column 2, for the INP104 DHE formulation.
Claim 10 that limits claim 1 to a vial nonintegral to the device and configured to be attached thereto, threadably attachable to the device.
As noted above, Applicant’s working example relies upon the POD® device and similarly INDP104 DHE as per Silberstein 2019 also relies upon the same device. Accordingly, the limitations of claim 10 would be present in the disclosure of Silberstein 2019
Claim 11 reciting the limitation of wherein each of the doses of the pharmaceutical composition comprises no more than 2.0 mg DHE or salt thereof. Silberstein 2019 Figure 5, notes POD® dose delivery of DHE 1.45 mg.
Claim 12 limiting claim 1 in to subdivided doses wherein each of the two divided sub doses volume is 140-250 μL As noted above, Applicant’s working example relies upon the POD® device and similarly INDP104 DHE as per Silberstein 2019 also relies upon the same device. Accordingly, the limitations of claim 12 with regard to actuated divided sub dose volume would be present in the disclosure of Silberstein 2019, as the same device would actuate the same sub dose volume claimed.
Claims 13-17, which depend from claim 1 and require a concentration of DHE mesylate salt between 2.5-7.5 mg/ml, caffeine 10mg/ml and dextrose 50 mg/ml, Silberstein 2019 discloses that Migranal DHE is in a glass vial containing DHE mesylate
4 mg, caffeine (anhydrous) 10 mg, dextrose (anhydrous) 50 mg, carbon dioxide, and water up to 1 mL, see page 44, column 2, last paragraph. As noted by Silberstein 2019, INP104 DHE administered via the POD® system used this Migranal DHE formulation that meets the limits of the claimed invention.
Claim 18 limits the method to a subject that has at least three migraine attacks in the 4-week period immediately preceding administration of the first dose. While not necessarily reciting this limitation, Silberstein 2019 teaches the necessity of treating acute migraine attacks, see page 42, column 2.
Silberstein 2019 discloses that migraine is known to impact individuals for those 15-49 year of age with substantial lot productivity and functionality with reduced quality of life, see page 42, column 1, Section entitled Migraine. Because migraine is known to be a lifetime disorder afflicting subject’s quality of life over the years, it would be obvious to administer the migraine reduction taught by Silberstein 2019 to address migraine attacks at the frequency of claim 18.
Claims 19-25 and 27, and require where the subject has fewer migraine headaches immediately following administration of the first dose, second dose and repeated administrations, and reduction of one or more symptoms occurs at 2 hours post administration, and the percentage reductions of migraine headache frequency during the 4 week period comparing the 2nd dose as compared to the first dose, as these properties would be necessarily present to the taught method of administering the same Migranal DHE formulation to a subject via the same POD® intranasal delivery device.
Regarding claim 26 and the requirement of the limitation of reduction of one more symptoms selected from pain, nausea, phonophobia and photophobia from the administration of the first dose, Silberstein 2019 discloses that Migranal DHE is known to reduce headache pain at 2 hours or 4 hours, see page 45, column 1.
Regarding claim 28 that requires the limitation that the patient does not respond to triptans, Silberstein discloses that DHE is indicated for those patients with recurrent/prolonged migraine and experiencing allodynia who are often less responsive to triptans, see page 43, column 2.
Regarding claim 30, that requires that the dose schedule last at least two month, Silberstein 2019 discloses that migraine is known to impact individuals for those 15-49 year of age with substantial lot productivity and functionality with reduced quality of life, see page 42, column 1, Section entitled Migraine. Because migraine is known to be a lifetime disorder afflicting subject’s quality of life over the years, it would be obvious to administer the claimed migraine reduction therapy at dose schedules of at least one or two months as claimed.
Claims 1-28 and 30 is/are rejected under 35 U.S.C. 103 as being unpatentable over Silberstein et al. “Dihydroergotamine (DHE) – Then and Now: A Narrative Review,” Headache: The Journal of Head and Face Pain Volume 60, Issue 1 Pages: 40-57 First Published: 17 November 2019 (Silberstein 2019) as evidenced by Cady 2015 Excerpt from Headache and Migraine Biology and Management, 2015 and Aurora et al. A randomized, double blind, placebo-controlled study of MAP0004 in adult patients with migraine. Headache. 2009;49:826-837, in view of Web Article Intranasal Drug Delivery 2016. Web Article Intranasal Drug Delivery 2016 was cited by the Examiner in the parent application of this case, 17148154.
While Silberstein 2019 as evidenced by Cady 2015 and Aurora 2009 teach the invention of claims 1-6, 8-28 and 30, they do not disclose the particular species of two divided subdoses into separate nostrils of claim 1, as detailed by claim 7. This is corrected by Therapeutic Intranasal Drug Delivery as follows.
Claim 7 further limits the invention, and requires that two divided subdoses administered into separate nostrils. While such limitation is not expressly disclosed by Silberstein 2019, it is noted that Web article Therapeutic Intranasal Drug Delivery 2017, discloses that typically with intranasal delivery of medicines, subdivided doses into two nostrils is preferred so as to double the absorptive surface area of the subject’s nose. See page 5, Section: Key points concerning bioavailability. The rationale to support a finding of obviousness is the combination of prior art elements as per Silberstein 2019 as evidenced by Cady in view Intranasal Drug Delivery 2016.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-28 and 30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11185497 B2, (cited on the IDS of parent case), as evidenced by Katsarava et al. Curr Pain Headache Rep. 2012; 16(1): 86–92, Published online 2011 Nov 15, in view of Silberstein et al. CNS Drugs (2013) 27:385–394, as evidenced by Aurora et al. A randomized, double blind, placebo-controlled study of MAP0004 in adult patients with migraine. Headache. 2009;49:826-837 and US 20170196861 A1. Katsarava, US 20170195861 and Silberstein 2019 were cited by the Examiner in the parent application of this case, 17148154.
Although the claims at issue are not identical, they are not patentably distinct from each other because, Examined claim 1 is as follows:
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Claims 2-3 recites an intranasal administration, and are directed to a manually activated, propellant driven, metered dose administration device. Claim 5 recites a repeat dose schedule of at least a first and a second dose of the pharmaceutical composition. Claim 6 recites each dose is administered as two divided subdoses, divided into separate nostrils. Claim 7 is directed to a method wherein each of the doses is administered as two divided subdoses, wherein the divided subdoses are administered into separate nostrils. Claim 14 is directed to a liquid formulation comprising 2.5-7.5 mg/ml DHE mesylate.
Regarding claims 1-3, 5-7 and 14, the 497 reference patent claims a method of acutely treating migraine headache with or without aura, comprising:
administering, via a manually actuated, metered-dose, propellant-driven intranasal delivery device, to a subject with migraine headache an effective dose of a liquid pharmaceutical composition comprising 4 mg/mL of dihydroergotamine (DHE) mesylate
wherein the effective dose comprises 1.45 mg of DHE mesylate administered as two divided doses of one spray per each nostril without requiring a timed wait between the two divided doses, and
wherein the manually actuated, metered-dose, propellant-driven intranasal delivery device is configured to sequentially release the liquid pharmaceutical composition followed by propellant, and
wherein, following administration of the dose, the mean DHE Cmax in plasma is at least 750 pg/ml; the time to Cmax (T max) of DHE in plasma is less than 45 minutes; and the mean plasma AUC 0-inf of DHE is at least 2500 pg*hr/ml, see claim 1.
Thus, claims 1-3, 5-7 and 14 with regard to the claimed method of treating migraines via intranasal formulations in divided doses comprising DHE mesylate with a concentration of 4 mg/ml into each nostril by the claimed delivery device is taught by claim 1 of the 497 patent.
Regarding the treatment of frequent episodes of migraines, it would be obvious to do so as a form of migraine is known as episodic migraine as evidenced by Katsarava. Episodic migraines are known in the art. “Episodic migraine (EM) is characterized by those with migraine who have 0 to 14 headache days per month,” see Katsarava3 page 86, column 2. This definition of episodic migraines provides one of ordinary skill in the art to treat frequent migraines (at least two migraines/month see paragraph 72 of the specification) as presently claimed.
Regarding the limitation of reducing frequent migraine headaches, while the treatment of frequent headaches is not necessarily claimed by the reference 497 patent, they are known to one of ordinary skill in the art and would be treated by DHE, as supported by Katsarava disclosing treatment of episodic migraines with ergot derivatives (i.e. DHE), see page 90, column 1. The rationale to support a finding of obviousness are the elements of the 497 patent (the method as claimed) as evidenced by Katsarava (treatment of frequent/episodic migraine) to predictably arrive at the claimed invention.
With regard to the limitation where the repeat schedule lasts at least one month, Silberstein 2019 teaches a randomized double-blind placebo-controlled Phase 2 study in acute migraine patients with MAP004 DHE. See page 45, column 2 bridging to page 46, column 1. This Phase 2 study, referenced by Silberstein 2019 is detailed by Aurora 2009, noting it was conducted at 9 headache centers in the U.S., in adult men and women with a documented history of acute migraine for at least 12 months. See abstract Aurora. A PHOSITA would routinely treat a subject with a repeat schedule of at least one month, where such subjects have a history of migraines for at least 12 months.
Prior to the filing of the present patent application, it would have been prima facie obvious to a PHOSITA following the teachings of the reference 497 patent as modified by Katsarava to predictably arrive at the claimed invention. The PHOSITA would have had a reasonable expectation of success because the combination of prior art elements (treatment of migraine with DHE via intranasal formulations in divided doses per the reference patent, including frequent/episodic episodes per Katsarava) to yield predictable results (i.e., the claimed invention).
Note that the 497 reference patent, as evidenced by Katsarava, teach the limitations of claim 1, they do not recite the particular limitations of the species of claim 1. However, these species are rendered obvious by US Pub 861 and Silberstein 2019. Prior the filing of examined application, it would have been obvious to a PHOSITA following the teachings of reference 497 patent evidenced by Katsarava, in view of US Pub 861 and Silberstein 2019, to arrive at the claimed species below with a reasonable expectation of success because the cited prior art all are directed to the treatment of migraines as claimed with DHE.
Regarding claim 4 and the limitation of DHE administered via a pulmonary route, US Pub 861 discloses a method of providing migraine therapy to a human subject, said method comprising: administering via pulmonary administration by oral inhalation, see claim 1. See also claim 1 of the reference patent noting administration via the respiratory route.
Claims 8-9, that require the limitation of hydroxy fluoroalkane (HFA) propellant, Silberstein 2019 discloses the use of the POD® intranasal delivery device that use HFA propellant, see page 47, column 2, for the INP104 DHE formulation.
Claim 10 that limits claim 1 to a vial nonintegral to the device and configured to be attached thereto, threadably attachable to the device.
As noted above, Applicant’s working example relies upon the POD® device and similarly INDP104 DHE as per Silberstein 2019 also relies upon the same device. Accordingly, the limitations of claim 10 would be present in the disclosure of Silberstein 2019.
Regarding claim 11 wherein each of the doses of the pharmaceutical composition comprises no more than 2.0 mg DHE or salt thereof, the 497 patent discloses wherein the effective dose comprises 1.45 mg of DHE mesylate administered as two divided doses of one spray per each nostril, see claim 1.
Claim 12 limiting claim 1 in to subdivided doses wherein each of the two divided sub doses volume is 140-250 μL As noted above, Applicant’s working example relies upon the POD® device and similarly INDP104 DHE as per Silberstein 2019 also relies upon the same device. Accordingly, the limitations of claim 12 with regard to actuated divided sub dose volume would be present in the disclosure of Silberstein 2019, as the same device would actuate the same sub dose volume claimed.
Regarding claim 13 and the limitation of DHE salt, the 497 patent discloses DHE mesylate salt, see claim 1.
Claims 13-17, which depend from claim 1 and require a concentration of DHE mesylate salt between 2.5-7.5 mg/ml, caffeine 10mg/ml and dextrose 50 mg/ml, Silberstein 2019 discloses that Migranal DHE is in a glass vial containing DHE mesylate
4 mg, caffeine (anhydrous) 10 mg, dextrose (anhydrous) 50 mg, carbon dioxide, and water up to 1 mL, see page 44, column 2, last paragraph. As noted by Silberstein 2019, INP104 DHE administered via the POD® system used this Migranal DHE formulation that meets the limits of the claimed invention.
Regarding claim 18 and the limitation of wherein the subject has at least 3 migraine attacks in the 4-week period immediately preceding administration of the 1st dose, US Pub 861 discloses that prophylactic medication may be selected for a patient having two to four headaches per month, see paragraph 6.
Regarding claims 19-25 and 27, where the subject has fewer migraine headaches immediately following administration of the first dose, second dose and repeated administrations, and reduction of one or more symptoms occurs at 2 hours post administration, as these properties would be necessarily present to the claimed method, claims 19-25 and 27 are rendered obvious by the cited prior art.
Regarding claim 26 and the requirement of the limitation of reduction of one more symptoms selected from pain, nausea, phonophobia and photophobia from the administration of the first dose, Silberstein 2019 discloses that Migranal DHE is known to reduce headache pain at 2 hours or 4 hours, see page 45, column 1.
Regarding claim 28 and the use of DHE nasal formulations of claim 1 to treat migraine in triptan non-responders, Silberstein discloses “DHE may also be an important option for triptan non-responders,” see page 385, column 1. Silberstein discloses
A retrospective chart review evaluated response in 84 triptan non-responders for whom data on response to a subsequent trial with DHE nasal spray were available [15]. Triptan nonresponse was defined as failing to achieve complete response to one or more triptans. Complete response occurred in 39 % of previous triptan non-responders when treated with DHE, supporting the theory that at least some triptan non-responders may respond to acute treatment with DHE, Id.
Regarding claim 30, that requires that the dose schedule last at least two month, Silberstein 2019 discloses that migraine is known to impact individuals for those 15-49 year of age with substantial lot productivity and functionality with reduced quality of life, see page 42, column 1, Section entitled Migraine. Because migraine is known to be a lifetime disorder afflicting subject’s quality of life over the years, it would be obvious to administer the claimed migraine reduction therapy at dose schedules of at least one or two months as claimed.
Conclusion and Communication
In summary, no claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to WILLIAM LEE whose telephone number is (571)270-3876. The examiner can normally be reached M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Adam C. Milligan can be reached at (571) 270-7674. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/WILLIAM Y LEE/Examiner, Art Unit 1623
/ADAM C MILLIGAN/Supervisory Patent Examiner, Art Unit 1623
1 CONTINUING DATA
This application is a CON of 17/148,154 01/13/2021 ABN
17/148,154 has PRO 62/961,076 01/14/2020
2 https://pubmed.ncbi.nlm.nih.gov/19545249/
3 Curr Pain Headache Rep (2012) 16:86–92
Prosecution Insights