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 .
This is the First Office Action on the Merits of US 18/276,724 filed on 08/10/2023 which is a 371 of PCT/US2022/017551 filed on 02/23/2022 which claims US priority benefit of US Provisional 63/153,122 filed on 02/24/2021.
Claim status
Claims 2, 10-11, 13-14, 19, 28-29, 31-32, 34, 36, 39-47, 49-50, 53, 56, 59-60, 62-68, 70-73, 75-76, 78-81, 83-84 are cancelled.
Claims 1, 3-9, 12, 15-18, 20-27, 30, 33, 35, 37-38, 48, 51-52, 54-55, 57-58, 61, 69, 74, 77, and 82 are pending and under examination.
Nucleotide and/or Amino Acid Sequence Disclosures
Requirements for patent applications containing nucleotide and/or amino acid sequence disclosures: Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows: Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Information Disclosure Statement
The IDS statements filed on 08/26/2025, 02/03/2025, 10/21/2024, 09/09/2024, and 09/11/2023 have been considered by the examiner.
Claim Objections
Claims 3 and 69 are objected to because of the following informalities:
Claims 3 and 35 recite improper grammar: “fewer or no side effects than”.
Regarding claims 69, the abbreviated term BAC should be written in full-length the first time it appears in the claims. Also, a space should be present between the terms “0.1” and “mg/mL” throughout the claim.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 1, 3-9, 12, 15-18, 20-27, 30, 33, 35, 37-38, 48, 51-52, 54-55, 57-58, 61, 69, 74, 77, and 82 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Base claim 1 (part a) recites “the therapeutically effective dosing regimen when administered alone by a non-nasal route of administration”. There is insufficient antecedent basis for this phrase because there is no prior reference in the claim to a therapeutically effective dosing regimen of a somatostatin mimetic when administered alone by a non-nasal route of administration. Also, claim 1 (part b) recites “the therapeutically effective dose when administered alone”. There is insufficient antecedent basis for this phrase because there is no prior reference in the claim to a therapeutically effective dose of a carbonic anhydrase inhibitor when administered alone. No therapeutically effective dosing regimen of a somatostatin mimetic when administered alone by a non-nasal route of administration or has been established. Also, no therapeutically effective dose of a carbonic anhydrase inhibitor when administered alone has been established. The claim requires a comparison of two unknown parameters.
Claims 3-9, 12, 15-18, 20-27, 30, 69, and 74 are indefinite as they depend from claim 1 and are not remedial.
Base claim 33 (part a) recites “the therapeutically effective dosing regimen when administered alone by a non-nasal route of administration”. There is insufficient antecedent basis for this phrase because there is no prior reference in the claim to a therapeutically effective dosing regimen of a somatostatin mimetic when administered alone by a non-nasal route of administration. Also, claim 33 (part b) recites “the therapeutically effective dose when administered alone”. There is insufficient antecedent basis for this phrase because there is no prior reference in the claim to a therapeutically effective dose of a carbonic anhydrase inhibitor when administered alone. No therapeutically effective dosing regimen of a somatostatin mimetic when administered alone by a non-nasal route of administration or has been established. Also, no therapeutically effective dose of a carbonic anhydrase inhibitor when administered alone has been established. The claim requires a comparison of two unknown parameters.
Claims 35, 37-38, 48, 51-52, 54-55, 57-58, 61, 77, and 82 are indefinite as they depend from claim 33 and are not remedial.
Claims 4-5 each recite the limitation "the serum area-under-the-curve of an effective unit dose of the somatostatin mimetic administered by a non-intranasal route" in lines 3-4. There is insufficient antecedent basis for this limitation in the claims because there is no prior reference in the claims to a serum area-under-the-curve of an effective unit dose of the somatostatin mimetic administered by a non-intranasal route.
Claims 6, 9, and 12 are indefinite as they depend from claims 4 or 5 and are not remedial.
Further, regarding claims 17, and 51, it is unclear how a somatostatin mimetic can be somatostatin.
Regarding claim 25, the term “approved indications” is vague and renders the claim indefinite because one of ordinary skill in the art would not be able to determine what parameters of dosing would be encompassed by “effective to treat approved indications”. Also, there is insufficient antecedent basis for the phrase: “the dose level, dose frequency or combination thereof that is effective to treat approved indications”.
Claim 26 recites the limitation "the dose level, dose frequency, or combination thereof of a carbonic anhydrase inhibitor when administered alone " in lines 1-3. There is insufficient antecedent basis for this limitation in the claims because there is no prior reference in the claims to a dose level, dose frequency, or combination thereof of a carbonic anhydrase inhibitor when administered alone.
Claim 48 is unclear because the antecedent basis for the singular term “the unit dose” is unclear. Claim 48 depends from claim 33 which recites “one or more unit doses of a somatostatin mimetic” and “one or more unit doses of a carbonic anhydrase inhibitor”.
Regarding claims 74 and 82 the claims contain percentages which result in slightly more than 100%. For example, octreotide 0.5%, mannitol 95%, and lecithin 5%. It would be remedial to modify the recited amounts to total no more than 100% and to include the intended proper % parameters such as w/v.
Regarding claims 69 and 77, the term Avicel CL611 is a Trademark. See MPEP § 2173.05(u). Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a food grade stabilizer composed of microcrystalline cellulose (Cellulose gel) (E460), sodium carboxy methyl cellulose (Cellulose gum) (E466), accordingly, the identification/description is indefinite.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3-9, 12, 15-18, 20-26, 30, 33, 35, 37-38, 48, 51-52, 54-55, 57, and 61 are rejected under 35 U.S.C. 103 as being unpatentable over Matharu entitled “Cluster headache” (BMJ Clin Evid. 2010 Feb 9;2010:1212), in view of Scotton et al (“Topiramate is more effective than acetazolamide at lowering intracranial pressure” Cephalalgia 2019 Vol 39 No 2: pages 209-218), in view of Gadhave et al (IN-201721036278; IDS ref), in view of Sandoz-Erfindungen et al (WO-1993/017037; IDS ref), in view of Mamluk (WO2016/126830; IDS ref) in view of US 5,578,567 to Cardinaux et al.
Claim interpretation: Regarding claims 33, 35, 37-38, 48, 51-52, 54-55, 57-58, 61, 77, and 82, generally, the intended use of a product is not afforded patentable weight for purpose of applying prior art for the product. See MPEP § 2111.02 and § 2114.
Regarding base claims 1, 17, 33, and 51, Matharu discloses a method for treating idiopathic intracranial hypertension (IIH) or cluster headache in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of subcutaneous administration of the somatostatin mimetic, octrotide, and oral administration of the carbonic anhydrase inhibitor topiramate. (See Abstract.)
Also, regarding claim 33, “instructions” generally will not be afforded patentable weight for purpose of applying prior art for the product. See MPEP § 2112.01.
Further, Scotton et al disclose administering acetazolamide, topiramate, and octreotide at clinical doses equivalent to a single human dose and high doses equivalent to human daily dose in rat model subjects for treating idiopathic intracranial hypertension (IIH). Scotton et al disclosed that subcutaneous and oral administration of topiramate significantly lowered intracranial pressure whereas acetazolamide, and octreotide showed no significant results for subcutaneous and oral administration. See Abstract. Scotton et al disclose that acetazolamide is the most commonly used drug for IIH but has shown intolerable side effects in 19-485 of patients. Thus, alternative drugs such as topiramate and octreotide are also commonly prescribed to treat IIH. Scotton et al disclose that topiramate has known side effects and thus suggest finding lower doses is useful. Scotton et al disclose that octreotide has shown improvement in treating IIH patients. (See pages 209-216).
Regarding claims 3, Scotten et al discloses that the dosing regimen of the carbonic anhydrase inhibitor topiramate elicits fewer or no side effects than that elicited by the therapeutically effective dose when administered alone. (Abstract; pages 209-216).
Sandoz-Erfindungen discloses that the effective intranasal amount is administered daily (Pg. 16, last paragraph, an indicated daily dosage is in the range of from ca. 0.25 to 2mg nasally). Sandoz-Erfindungen discloses a method for treating cluster headache in a subject in need thereof (See ref claim 1, method for treating acute attacks of migraine or cluster headache in a subject in need of such therapy), comprising administering to the subject an effective intranasal amount of a somatostatin mimetic (See ref claim 1, administering nasally to said subject a therapeutically effective amount of a somatostatin peptide analogue or derivative), but fails to explicitly disclose formulated for direct nose-to-brain administration.
Sandoz-Erfindungen teaches that the effective intranasal amount is administered daily to treat cluster headache (Claim 1, method for treating acute attacks of migraine or cluster headache in a subject in need of such therapy comprising, administering nasally to said subject a therapeutically effective amount of a somatostatin peptide analogue or derivative; Pg. 16, last paragraph, an indicated daily dosage is in the range of from ca. 0.25 to 2mg nasally). Sandoz-Erfindugen discloses that the effective intranasal amount is less than the amount effective when the somatostatin mimetic is administered by a nonintranasal route in accordance with the same dosing regimen, the only difference between the claimed method and the method disclosed in Sandoz-Erfindugen is the intended outcome is stated to be different. Because the patient populations are the same and because the method steps for administering are the same, at least some subjects from each group will inherently result wherein the effective intranasal amount is less than the amount effective when the somatostatin mimetic is administered by a nonintranasal route in accordance with the same dosing regimen.
Regarding claims 4-5, 9 and 12, Sandoz-Erfindungen discloses that a serum area-under-the-curve from a unit dose of the intranasal amount of the somatostatin mimetic is less than the serum area-under-the-curve from an effective unit dose of the somatostatin mimetic administered by the intranasal route for an indication other than IIH or cluster headache. Sandoz-Erfindungen that a serum area-under-the-curve from a unit dose of the intranasal amount of the somatostatin mimetic is less than the serum area-under-the-curve of an effective unit dose of the somatostatin mimetic administered by a non-intranasal route, the only difference between the claimed method and the method disclosed in Sandoz-Erfindungen is the intended outcome is stated to be different. Because the patient populations are the same and because the method steps for administering are the same, at least some subjects from each group will inherently result wherein a serum area-under-the-curve from a unit dose of the intranasal amount of the somatostatin mimetic is less than the serum area-under-the-curve of an effective unit dose of the somatostatin mimetic administered by a non-intranasal route. Sandoz-Erfindugen discloses that a serum area-under-the-curve from a unit dose of the intranasal amount of the somatostatin mimetic is less than the serum area-under-the-curve from an effective unit dose of the somatostatin mimetic administered by the intranasal route for an indication other than IIH or cluster headache, the only difference between the claimed method and the method disclosed in Sandoz-Erfindugen is the intended outcome is stated to be different. Because the patient populations are the same and because the method steps for administering are the same, at least some subjects from each group will inherently result wherein a serum area-under-the-curve from a unit dose of the intranasal amount of the somatostatin mimetic is less than the serum area-under-the-curve from an effective unit dose of the somatostatin mimetic administered by the intranasal route for an indication other than IIH or cluster headache. Sandoz-Erfindungen discloses that the serum area-under-the-curve of the intranasal amount of the somatostatin mimetic is about equal to or less than about 50% of the serum area-under-the-curve of the somatostatin mimetic administered by a non-intranasal route, the only difference between the claimed method and the method disclosed in Sandoz-Erfindungen is the intended outcome is stated to be different. Because the patient populations are the same and because the method steps for administering are the same, at least some subjects from each group will inherently result wherein the serum area-under-the-curve of the intranasal amount of the somatostatin mimetic is about equal to or less than about 50% of the serum area-under-the-curve of the somatostatin mimetic administered by a non-intranasal route. Sandoz-Erfindungen discloses that the serum area-under-the-curve of the intranasal amount of the somatostatin mimetic is about equal to or less than about 25% of the serum area-under-the-curve of the somatostatin mimetic administered by a non-intranasal route, the only difference between the claimed method and the method disclosed in Sandoz-Erfindungen is the intended outcome is stated to be different. Because the patient populations are the same and because the method steps for administering are the same, at least some subjects from each group will inherently result wherein the serum area-under-the-curve of the intranasal amount of the somatostatin mimetic is about equal to or less than about 25% of the serum area-under-the-curve of the somatostatin mimetic administered by a non-intranasal route. Sandoz-Erfindungen discloses that the serum area-under-the-curve of the intranasal amount of the somatostatin mimetic is about equal to or less than about 10% of the serum area-under-the-curve of the somatostatin mimetic administered by a non-intranasal route, the only difference between the claimed method and the method disclosed in Sandoz-Erfindungen is the intended outcome is stated to be different. Because the patient populations are the same and because the method steps for administering are the same, at least some subjects from each group will inherently result wherein the serum area-under-the-curve of the intranasal amount of the somatostatin mimetic is about equal to or less than about 10% of the serum area-under-the-curve of the somatostatin mimetic administered by a non-intranasal route. Note that the serum area-under-the-curve of the intranasal amount of the somatostatin mimetic is about equal to or less than about 50% of the serum area-under-the-curve of the somatostatin mimetic administered by the intranasal route for an indication other than IIH or cluster headache, the only difference between the claimed method and the method disclosed in Sandoz-Erfindungen is the intended outcome is stated to be different. Because the patient populations are the same and because the method steps for administering are the same, at least some subjects from each group will inherently result wherein the serum area-under-the-curve of the intranasal amount of the somatostatin mimetic is about equal to or less than about 50% of the serum area-under-the-curve of the somatostatin mimetic administered by the intranasal route for an indication other than IIH or cluster headache. Further, the serum area-under-the-curve of the intranasal amount of the somatostatin mimetic is about equal to or less than about 25% of the serum area-under-the-curve of the somatostatin mimetic administered by the intranasal route for an indication other than IIH or cluster headache, the only difference between the claimed method and the method disclosed in Sandoz-Erfindungen is the intended outcome is stated to be different. Because the patient populations are the same and because the method steps for administering are the same, at least some subjects from each group will inherently result wherein the serum area-under-the-curve of the intranasal amount of the somatostatin mimetic is about equal to or less than about 25% of the serum area-under-the-curve of the somatostatin mimetic administered by the intranasal route for an indication other than IIH or cluster headache. Sandoz-Erfindungen discloses that the serum area-under-the-curve of the intranasal amount of the somatostatin mimetic is about equal to or less than about 10% of the serum area-under-the-curve of the somatostatin mimetic administered by the intranasal route for an indication other than IIH or cluster headache, the only difference between the claimed method and the method disclosed in Sandoz-Erfindungen is the intended outcome is stated to be different. Because the patient populations are the same and because the method steps for administering are the same, at least some subjects from each group will inherently result wherein the serum area-under-the-curve of the intranasal amount of the somatostatin mimetic is about equal to or less than about 10% of the serum area-under-the-curve of the somatostatin mimetic administered by the intranasal route for an indication other than IIH or cluster headache.
Further, regarding claims 4-5, 9 and 12, Gadhave discloses that a serum area-under-the-curve from a unit dose of the intranasal amount of the somatostatin mimetic is less than the serum area-under-the-curve from an effective unit dose of the somatostatin mimetic administered by the intranasal route for an indication other than IIH or cluster headache, the only difference between the claimed method and the method disclosed in Gadhave is the intended outcome is stated to be different. Because the patient populations are the same and because the method steps for administering are the same, at least some subjects from each group will inherently result wherein a serum area-under-the-curve from a unit dose of the intranasal amount of the somatostatin mimetic is less than the serum area-under-the-curve from an effective unit dose of the somatostatin mimetic administered by the intranasal route for an indication other than IIH or cluster headache.
Regarding claim 6, Mamluk disclose a method for treating idiopathic intracranial hypertension (IIH) in a subject in need thereof. (See para 0010). Mamluk disclose a method of treating acromegaly and other diseases and conditions, including idiopathic intracranial hypertension (IIH) and vascular headaches, in a subject. (See para 0068), Mamluk disclose a patient suffering from IIH), and administering to the subject an effective amount of a somatostatin mimetic. (See para 0010.) Mamluk disclose administering to the subject at least once daily at least one dosage form comprising an oily suspension comprising octreotide; Para. [0104], the formulation consists essentially of an oily suspension which comprises an admixture of a hydrophobic medium and a solid form wherein the solid form comprises a therapeutically effective amount of octreotide), but fails to explicitly disclose intranasal, and formulated for direct nose-to-brain administration.
Regarding claims 7, and 37, Matharu discloses that a non-intranasal route is subcutaneous. Matharu discloses a method for treating idiopathic intracranial hypertension (IIH) or cluster headache in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of subcutaneous administration of the somatostatin mimetic, octrotide (see Abstract).
Regarding claims 8, 15, 16, 38, 48, and 55, Gadhave is also in the field of methods for treating including intranasal administration of a somatostatin mimetic (See ref claim 1 and 8) and teaches formulated for direct nose-to-brain administration (See ref claim ). Gadhave disclose pharmaceutical composition for nasal administration, comprising: a protein or peptide drug, wherein the drug is a somatostatin analogue; a mucoadhesive agent, from 0.2-0,8% weight by volume, to increase retention time of the drug in the nasal cavity; Claim 8, method of treating a subject suffering from acromegaly, comprising intranasal administration to the said subject, the dosage form of claim 1; Claim 6, wherein intranasal delivery of the drug is adapted so as to target brain tissue).
Gadhave discloses that the effective intranasal amount of somatostatin mimetic is about equal to or less than about 100 mcg, 50mcg, 10 mcg, 5 mcg or 1 mcg daily. Regarding claim 15, Gadhave discloses that the effective intranasal amount of somatostatin mimetic is administered as a single daily dose, twice a day dosing, three times a day dosing, four times a day dosing, or as 2, 3 or 4 divided doses. Regarding claim 16, Gadhave discloses that the effective intranasal amount is administered daily for a duration effective to treat or resolve the IIH or cluster headache.
Regarding claim 38, Gadhave discloses that a unit dose of the somatostatin mimetic formulated for intranasal administration is about equal to or less than about 100 mcg, 50 mcg, 10 mcg, 5 mcg or 1 mcg. Regarding claim 48, Gadhave discloses that the unit dose is labeled for administration in a single daily dose, twice a day dosing, three times a day dosing, four times a day dosing, or as 2, 3 or 4 divided doses. Regarding claim 55, Gadhave discloses that a carbonic anhydrase inhibitor is administered once daily or twice daily.
Regarding claims 18 and 52, Gadhave discloses that the somatostatin mimetic formulated for intranasal administration comprises a powder, liquid or gel.
Regarding claim 20, Matharu discloses that treating is to reduce or prevent an acute, ongoing episode, and/or prophylactic and/or maintenance therapy to prevent future episodes. (See Abstract; entire article).
Regarding claims 21, 24, 30, and 54, Matharu discloses that a carbonic anhydrase inhibitor is administered orally. Matharu disclose oral administration of the carbonic anhydrase topiramate. (See Abstract.)
Regarding claim 22, Matharu, and Scotten and Sandoz-Erfindungen discloses that a carbonic anhydrase inhibitor is administered once daily or twice daily.
Regarding claim 23, the cited references do not disclose that the therapeutically effective combination is a synergistic combination but it is considered that finding a range of therapeutic doses that are synergistic would be considered routine optimization. Where 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 MPEP § 2144.05. Cited references discloses the general conditions therapeutic doses for the somatostatin mimetic and carbonic anhydrase inhibitor for treating IIH or cluster headaches. Therefore, the claimed limitation of doses being synergistic is considered optimization through routine experimentation, and would be obvious to one of ordinary skill in the art. Furthermore, a prima facie case of obviousness based on optimization may only be rebutted by evidence showing that the claimed range is critical, generally by proof that the claimed range achieves unexpected results relative to the prior art. See MPEP § 2144.05.
Regarding claims 24, 30, 57, and 61, Matharu and Sandoz-Erfindugen discloses that the carbonic anhydrase inhibitor is topiramate and the dosing regimen is equal to or less than about 50 mg once a day or twice a day; is about 25 mg once a day or twice a day; or about 15 mg once a day or twice a day.
However, Sandoz-Erfindugen does not explicitly disclose wherein the effective intranasal amount is about equal to or less than about 100 mcg daily.
Cardinaux is also in the field of methods of treating including nasal administration of somatostatin analogues (See Col. 2, Lns. 37-50; Col. 10, Lns. 16-21) and teaches wherein the effective intranasal amount is about equal to or less than about 100 mcg daily (See Col. 10, Lns. 30-34). Cardinaux teaches that the amount of active peptide will generally be chosen to provide effective treatment on administration once or 2 to 4 times/day. The physiologically active peptide may suitably be present in an amount such as to provide a free peptide concentration of from 0.01 to 100 mg per administration; (see Col. 2, Lns. 37-50). Cardinaux teaches administering a hPTH fragment having PTH-like activity to a subject requiring treatment therewith administering hPTH or said hPTH fragment via the nasal route, e.g. in the form of a composition as defined herein. (See Col. 10, Lns. 18-21). More preferred are somatostatin, and the derivatives or analogues thereof).
It would have been obvious to one of ordinary skill in the art at the time of the invention to combine the elements of Sandoz-Erfindugen to include about equal to or less than about 100 mcg daily as taught by Cardinaux. The motivation for doing so would have been to provide a dose equipotent to the injection route and thereby enhance treatment in the subject (See Col. 10, Lns. 27-38).
Regarding claim 25, Scotten discloses that the dose level, dose frequency, or combination thereof of a carbonic anhydrase inhibitor when administered alone elicits fewer side effects than elicited by the dose level, dose frequency or combination thereof that is effective to treat approved indications.
Regarding claim 26, Scotten discloses that the dose level, dose frequency, or combination thereof of a carbonic anhydrase inhibitor when administered alone elicits fewer side effects than elicited by the dose level, dose frequency or combination thereof that is effective to treat IIH or cluster headache.
Regarding claim 30, Scotten discloses that the carbonic anhydrase inhibitor is topiramate and the dosing regimen is equal to or less than about 50 mg once a day or twice a day, or about 25 mg once a day or twice a day, or about 15 mg once a day or twice a day.
Regarding claim 35, Scotten et al discloses that the dosing regimen of the carbonic anhydrase inhibitor elicits fewer or no side effects than that elicited by the therapeutically effective dose when administered alone.
However, while Matharu discloses subcutaneous administration of the somatostatin mimetic octreotide they do not specify intranasal administration of octreotide.
Mamluk discloses that the somatostatin mimetic is octreotide (Para. [0010]). Mamluk discloses administering to the subject at least once daily at least one dosage form comprising an oily suspension comprising octreotide).
Gadhave is also in the field of methods for treating including administration of a somatostatin mimetic (see ref claims 1 & 8). Gadhave teaches intranasal, and formulated for direct nose-to-brain administration (see ref claim 1). Gadhave teaches pharmaceutical compositions for nasal administration, comprising: a protein or peptide drug, wherein the drug is a somatostatin analogue; a mucoadhesive agent, from 0.2-0.8 weight by volume, to increase retention time of the drug in the nasal cavity (see ref claim 8). method of treating a subject suffering from acromegaly, comprising intranasal administration to the said subject, the dosage form of claim 1; Claim 6, wherein intranasal delivery of the drug is adapted so as to target brain tissue).
It would have been obvious to one of ordinary skill in the art at the time of the invention to combine the elements of Matharu, Mamluk, Sandoz-Erfindungen and Gadhave, to include intranasal and formulated for direct nose-to-brain administration as taught by Gadhave.
The motivation for doing so would have been to achieve better systemic bioavailability by reaching the central nervous system directly from the nasal cavity (See Gadhave page 8, lines 18-24).
Further, regarding the dose level limitations in the claims, one of ordinary skill in the art would have been motivated to combine a known therapeutic lower dose of the somatostatin octreotide (Matharu) with a known therapeutic lower dose of carbonic anhydrase inhibitor topiramate (Matharu) or acetazolamide (Scotten) where each of such doses are lower than known upper level effective doses for the rationale of using less of each component to reduce toxicity. Further, Sandoz-Erfindungen It would have been obvious to do such because the cited references suggest combining therapeutic doses at lower levels to achieve effective therapy treatments but with less toxicity to the patient. Sandoz-Erfindungen teaches that the effective intranasal amount is administered daily to treat cluster headache (Claim 1, method for treating acute attacks of migraine or cluster headache in a subject in need of such therapy comprising, administering nasally to said subject a therapeutically effective amount of a somatostatin peptide analogue or derivative; Pg. 16, last paragraph, an indicated daily dosage is in the range of from ca. 0.25 to 2mg nasally). Sandoz-Erfindugen discloses that the effective intranasal amount is less than the amount effective when the somatostatin mimetic is administered by a nonintranasal route in accordance with the same dosing regimen, the only difference between the claimed method and the method disclosed in Sandoz-Erfindugen is the intended outcome is stated to be different. Because the patient populations are the same and because the method steps for administering are the same, at least some subjects from each group will inherently result wherein the effective intranasal amount is less than the amount effective when the somatostatin mimetic is administered by a nonintranasal route in accordance with the same dosing regimen.
In view of the high skill level in the art before the effective filing date of the presently claimed invention it is considered that one of ordinary skill in the art would have had a reasonable expectation of success to combine the elements of the cited references to arrive at the presently claimed invention,
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Sandoz-Erfindungen to include formulated for direct nose-to-brain administration as taught by Gadhave.
The motivation for doing so would have been to achieve better systemic bioavailability by reaching the central nervous system directly from the nasal cavity (Gadhave Pg. 8, Lns. 18-24).
It would have been obvious to one of ordinary skill in the art at the time of the invention to modify Sandoz-Erfindungen to include for a duration effective to treat or resolve the IIH or cluster headache, since discovering the optimum value of a result effective variable involves only routine skill in the art.
The motivation for doing so would have been improve symptoms following administration and thereby provide complete relief to the subject (Pg. 15, Para. 2 - Pg. 16, last paragraph). Regarding claim 18, modified Sandoz-Erfindunger discloses the method of claim 2 wherein the somatostatin mimetic formulated for intranasal administration comprises a powder, liquid or gel (Claim 1, administering nasally to said subject a therapeutically effective amount of a somatostatin peptide analogue or derivative; Pg. 11, Para. 3, Preferably the compounds of the invention may be administered in the form of a powder). Regarding claim 19, modified Sandoz-Erfindungen discloses the method of claim 2. In regards to wherein the effective intranasal amount of somatostatin mimetic provides a minimal effective dose, the only difference between the claimed method and the method disclosed in Sandoz-Erfindungen is the intended outcome is stated to be different. Because the patient populations are the same and because the method steps for administering are the same, at least some subjects from each group will inherently result wherein the effective intranasal amount of somatostatin mimetic provides a minimal effective dose.
Sandoz-Erfindungen discloses that treating is to reduce or prevent an acute, ongoing episode, and/or prophylactic and/or maintenance therapy to prevent future episodes (Claim 1, method for treating acute attacks of migraine or cluster headache in a subject in need of such therapy comprising, administering nasally to said subject a therapeutically effective amount of a somatostatin peptide analogue or derivative).
Gadhave discloses a method for treating in a subject in need thereof (Claim 8, method of treating a subject suffering from acromegaly), comprising administering to the subject an effective intranasal amount of a somatostatin mimetic formulated for direct nose-to-brain administration (see ref claim 8, method of treating a subject suffering from acromegaly, comprising intranasal administration to the said subject, the dosage form of claim 1; ref claim 6, wherein intranasal delivery of the drug is adapted so as to target brain tissue; ref claim 1. pharmaceutical composition for nasal administration, comprising: a protein or peptide drug, wherein the drug is a somatostatin analogue; a mucoadhesive agent, from 0.2-0.8 % weight by volume, to increase retention time of the drug in the nasal cavity), but fails to explicitly disclose cluster headache.
Sandoz-Erfindungen is also in the field of methods of treating including intranasal administration of a somatostatin analogue (Sandoz-Erfindungen ref claim 1) and teaches cluster headache (Sandoz-Erfindungen Claim 1, method for treating acute attacks of migraine or cluster headache in a subject in need of such therapy comprising, administering nasally to said subject a therapeutically effective amount of a somatostatin peptide analogue or derivative; Pg. 16, last paragraph, an indicated daily dosage is in the range of from ca. 0.25 to 2mg nasally).
Gadhave discloses that the indication other than IIH or cluster headache is acromegaly or carcinoid syndrome (See ref claim 8, stating a method of treating a subject suffering from acromegaly, comprising intranasal administration to the said subject, the dosage form of ref claim 1). Gadhave discloses that intranasal delivery of the drug is adapted so as to target brain tissue. For example, ref claim 1 recites pharmaceutical composition for nasal administration, comprising: a protein or peptide drug, wherein the drug is a somatostatin analogue; a mucoadhesive agent, from 0.2-0.8% weight by volume, to increase retention time of the drug in the nasal cavity. Gadhave discloses that The drug can be transported through olfactory neuron cells by intracellular axonal transport primarily to the olfactory bulb. The route can be exploited for the treatment of diseases where rapidly achieved and high concentrations of drug in the brain are essential. The current invention includes the treatment of acromegaly with a nasal Octreotide formulation. (See Pg. 8, Lns. 12-17).
Further, it would have been obvious to one of ordinary skill in the art at the time of the invention to combine the elements of the cited references and Gadhave to include cluster headache as taught by Sandoz-Erfindungen. The motivation for doing so would have been to provide treatment for a prolonged period of craniofacial pain attacks with good efficacy no harmful side effects (Sandoz-Erfindungen Pg. 9, Paras. 1-2).
In view of the high skill level in the art before the effective filing date of the presently claimed invention it is considered that one of ordinary skill in the art having the cited references would have had a reasonable expectation of success to combine the elements of the cited references to arrive at the presently claimed invention.
Claims 1, 33, 74, and 82 are rejected under 35 U.S.C. 103 as being unpatentable over Matharu entitled “Cluster headache” (BMJ Clin Evid. 2010 Feb 9;2010:1212), in view of Scotton et al (“Topiramate is more effective than acetazolamide at lowering intracranial pressure” Cephalalgia 2019 Vol 39 No 2: pages 209-218), in view of Gadhave et al (IN-201721036278; IDS ref), in view of Sandoz-Erfindungen et al (WO-1993/017037; IDS ref), in view of Mamluk (WO2016/126830; IDS ref) in view of US 5,578,567 to Cardinaux et al, as applied to claims 1 and 33 above, in view of Colombo et al (FR 2774290 A1 published 08/06/1999).
Claims 1 and 33 are rendered obvious over Matharu, in view of Scotton et al, in view of Gadhave et al, in view of Sandoz-Erfindungen et al, in view of Mamluk (WO2016/126830; IDS ref) in view of US 5,578,567 to Cardinaux et al for reasons provided above.
Regarding claims 74 and 82, the combination of references above disclose the effective dose to administer octreotide by nasal administration but do not explicitly disclose a powder pharmaceutical comprising octreotide 0.1%, mannitol 95%, lecithin 5%.
Colombo et al a powder pharmaceutical for nasal administration comprising the active compound with about 95% mannitol and about 5% lecithin. (See Example 2).
In view of the high skill level in the art before the effective filing date it would have been obvious to use the active ingredient octreotide in a powder pharmaceutical containing mannitol and lecithin because Colombo et al suggests this formulation for administering a therapeutic nasal powder. One of ordinary skill in the art would have been motivated to do such for the rationale of making a powder suitable for nasal administration because as shown in the cited references the administration of octreotide by nasal administration was preferred.
Thus it is considered that one of ordinary skill in the art having the cited references before the effective filing date would have had a reasonable expectation of result to combine the elements of the cited references to arrive at the presently claimed invention.
Claims 1, 33, 69, and 77 are rejected under 35 U.S.C. 103 as being unpatentable over Matharu entitled “Cluster headache” (BMJ Clin Evid. 2010 Feb 9;2010:1212), in view of Scotton et al (“Topiramate is more effective than acetazolamide at lowering intracranial pressure” Cephalalgia 2019 Vol 39 No 2: pages 209-218), in view of Gadhave et al (IN-201721036278; IDS ref), in view of Sandoz-Erfindungen et al (WO-1993/017037; IDS ref), in view of Mamluk (WO2016/126830; IDS ref) in view of US 5,578,567 to Cardinaux et al, as applied to claims 1and 33 above, in view of Cohen-Vered et al (US2004/0180059 published 09/16/2004).
Claims 1 and 33 are rendered obvious over Matharu, in view of Scotton et al, in view of Gadhave et al, in view of Sandoz-Erfindungen et al, in view of Mamluk (WO2016/126830; IDS ref) in view of US 5,578,567 to Cardinaux et al for reasons provided above.
Regarding claims 69 and 77, the combination of references above disclose the effective dose to administer octreotide by nasal administration but do not explicitly disclose a liquid/gel pharmaceutical composition comprising PEG 400, polysorbate 80, and citrate buffer.
Cohen-Vered et al disclose liquid/gel pharmaceutical formulations for therapeutic peptides comprising PEG 400, polysorbate 80, and citrate buffer. (See para 0238; Table 2).
In view of the high skill level in the art before the effective filing date it would have been obvious to use the active ingredient octreotide in a liquid/gel pharmaceutical containing PEG 400, polysorbate 80, and citrate buffer because Cohen-Vered et al suggests this formulation for administering a therapeutic liquid/gel. One of ordinary skill in the art would have been motivated to do such for the rationale of making a pharmaceutical formulation suitable for administering a therapeutic peptide.
Thus it is considered that one of ordinary skill in the art having the cited references before the effective filing date would have had a reasonable expectation of result to combine the elements of the cited references to arrive at the presently claimed invention.
Double Patenting
Claims 1, 3-9, 12, 15-18, 20-27, 30, 33, 35, 37-38, 48, 51-52, 54-55, 57-58, 61, 69, 74, 77, and 82 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9, 12, 15, 17-18, 20-26, 34-40, and 42 of copending Application No. 18/273,336 in view of Matharu (above), in view of Scotton et al (above).
Although the copending claims are not identical to the instant claims they are not patentably distinct because the combination of copending claims in view of Matharu and Scotton et al renders obvious the instant claims.
Regarding instant claims 1, 3-9, 12, 15-18, 20-27, 30, 33, 35, 37-38, 48, 51-52, 54-55, 57-58, 61, 69, 74, 77, and 82, the co-pending claims 1-9, 12, 15, 17-18, 20-26, 34-40, and 42 recite essentially the identical limitations as the instant claims except that the copending claims do not recite the second component of a carbonic anhydrous inhibitor (instant base claims 1 and 33), or specifically the carbonic anhydrous inhibitor being topiramate or acetazolamide (instant claims 24, 27, 30, 57-58, and 61).
Regarding instant claims, Matharu discloses a method for treating idiopathic intracranial hypertension (IIH) or cluster headache in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of subcutaneous administration of the somatostatin mimetic, octrotide, and oral administration of the carbonic anhydrase inhibitor topiramate. (See Abstract.) Matharu discloses that the carbonic anhydrase inhibitor is topiramate and the dosing regimen is equal to or less than about 50 mg once a day or twice a day; is about 25 mg once a day or twice a day; or about 15 mg once a day or twice a day.
Scotton et al disclose administering acetazolamide, topiramate, and octreotide at clinical doses equivalent to a single human dose and high doses equivalent to human daily dose in rat model subjects for treating idiopathic intracranial hypertension (IIH). Scotton et al disclosed that subcutaneous and oral administration of topiramate significantly lowered intracranial pressure whereas acetazolamide, and octreotide showed no significant results for subcutaneous and oral administration. See Abstract. Scotton et al disclose that acetazolamide is the most commonly used drug for IIH but has shown intolerable side effects in 19-485 of patients. Thus, alternative drugs such as topiramate and octreotide are also commonly prescribed to treat IIH. Scotton et al disclose that topiramate has known side effects and thus suggest finding lower doses is useful. Scotton et al disclose that octreotide has shown improvement in treating IIH patients. (See pages 209-216).
One of ordinary skill in the art would have been motivated to combine a known therapeutic dose of carbonic anhydrase inhibitor topiramate (Matharu) or acetazolamide (Scotten et al) with the therapeutic composition of the copending claims for the rationale of using less of each component to reduce toxicity. It would have been obvious to do such because the toxicity disclosed in Matharu and Scotten suggests combining therapeutic doses at lower levels to achieve effective therapy treatments but with less toxicity to the patient.
In view of the high skill level in the art before the effective filing date of the presently claimed invention it is considered that one of ordinary skill in the art would have had a reasonable expectation of success to combine the elements of the copending claims with the elements of the cited references to arrive at the presently claimed inventon,
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
Related art which may be applied in a future office action if appropriate:
Mamluk et al (US 2016/0220628);
Matharu and Silver “Cluster headache” BMJ Clin Evid 2008 Feb 15: Abstract only)
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/CATHERINE S HIBBERT/Primary Examiner, Art Unit 1658