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 .
Claim Status
Claims 1, 3-10, 13-16, and 18-20 are pending and under examination.
Priority
This application is filed 11/23/2022 and is a Continuation of 16/985,187, filed 08/04/2020, now abandoned
16/985,187 is a Continuation of PCT/IB2019/050901, filed 02/05/2019,
claims foreign priority to 201841008091, filed 03/05/2018,
claims foreign priority to 201841004306, filed 02/05/2018.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. 16/985,187, filed on 08/04/2020.
Information Disclosure Statement
The Information Disclosure Statement(s) filed 4/28/2023 and 8/28/2023 have been considered by the Examiner. The submission(s) is/are in compliance with the provisions of 37 CFR §§ 1.97 and 1.98. Enclosed with this Office Action is a return-copy of the Forms PTO-1449 with the Examiner’s signature and indication of those references that have been considered.
Claim Objections
Claims 1, 3, 7, 9, 14, and 16 are objected to because of the following informalities:
Claims 1, 7 and 14 are labeled as “Original” but contain markings indicating that these claims are “currently amended”. Claims should be marked properly according to 37 C.F.R. 1.121.
Claim 1,
line 6: the term “Wherein” should be rewritten in all lowercase letters;
line 12: the space between “naphthalene-2-” and “nicotinic acid” should be deleted;
lines 14-15: the phrase “omega 3 fatty acids, omega 6 fatty acids” should be “omega-3 fatty acids, omega-6 fatty acids”.
Claim 3,
line 7: the meaning of abbreviations should be spelled out at least once in the claims and when it first appears. Specifically, "PHMB" is not frequently used, readily identifiable abbreviation whose full name should be spelled out.
Claim 6,
line 2: the term “the compounds" clearly refer back to the components of parts a) and b) in Claim 1 but the term "the compounds" should have explicit antecedence instead of only referring back to the formulas of the compounds. This problem is not considered to rise to the level of indefiniteness because when given its broadest reasonable interpretation, a POSA can reasonably discern the meaning.
Claim 7,
line 12: the space between “naphthalene-2-” and “nicotinic acid” should be deleted;
lines 14-15: the phrase “omega 3 fatty acids, omega 6 fatty acids” should be “omega-3 fatty acids, omega-6 fatty acids”.
Claim 9,
line 7: the meaning of abbreviations should be spelled out at least once in the claims and when it first appears. Specifically, "PHMB" is not frequently used, readily identifiable abbreviation whose full name should be spelled out.
Claim 14,
line 10: the space between “naphthalene-2-” and “nicotinic acid” should be deleted;
lines 14-15: the phrase “omega 3 fatty acids, omega 6 fatty acids” should be “omega-3 fatty acids, omega-6 fatty acids”;
Appropriate correction is required.
Claim Rejections - 35 USC § 112 - Indefiniteness
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 3-10, 13-16, and 18-20 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.
Claim 1 is indefinite because it fails to inform, with reasonable certainty, whether the claimed subject matter of Claim 1 (part a) is: 1) a single chemical compound or 2) a composition or association of two separate components. The claim ambiguity arises from the interaction between: the structural depiction of Formula I, the recitation of “salt or stereoisomer”, and the definition and placement of RH. One can interpret Claim 1 (part a) as referring to a single compound wherein Formula I represents a discrete molecular entity and RH treated as a counterion or substituent within a single chemical structure. While another may interpret Claim 1 (part 1) as referring to a two-component system wherein Formula I represents a base compound and RH represents a separate molecular species (e.g., omega-3 fatty acid, n-acetyl cysteine, etc.) in a composition or association of two components rather than a single compound. Both interpretations are reasonable because RH is defined to include entire bioactive molecules, not merely simple counterions. Additionally, RH is shown as part of Formula I, implying covalent incorporation, while being defined as other whole molecules such as n-acetylcysteine or acids including fatty acids in Claim 1 (part a). In addition to the backdrop outlined above, the phrase “a salt or a stereoisomer of a formula of Formula I
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”, is circular because the structure of Formula I is already drawn as a stereoisomer as such it is illogical that one would be selecting a “salt or stereoisomer” from a stereoisomer. Furthermore, the claim treats the “salt” and “stereoisomer” as equally having the formula of Formula I. A POSA is forced to guess whether Formula I is meant to depict: the free base only, the salt pair or some representation covering both.
A similar issue of ambiguity occurs in Claim 1 (part b) for Formula V.
Accordingly, for the above reasons, Claims 7 and 14 are also rejected as being indefinite.
In Claim 3, the phrase “wherein lipoic acid is a compound of Formula IV, or a salt or stereoisomer thereof, wherein RH is…” is indefinite. The term “lipoic acid” is a well-defined complete molecule in the arts with its own distinct structure, not a variable scaffold as claimed. It does not inherently contain variable substituent RH. And similar to Claim 1, Formula IV is drawn to a structurally defined stereoisomer yet recites “a salt or stereoisomer thereof”. RH in claim 3 includes ions and entire molecules and polymers, and is even “null” which leaves Formula IV as an ion itself. For similar reasons, Claim 9 is also indefinite.
Claim 10 depends from Claim 7 and recites "a compound of Formula IV". However, Formula IV is not defined in either claim.
Claims 14 and 16 recite “or a physical mixture thereof” at the end of the claim. This is indefinite because it is not clear if the physical mixture thereof modifies only Formula IV or the entire composition.
Claims 4-6, 8, 13, 15, and 18-20 are also indefinite since the do not render the claimed invention definite.
For the reasons given above, one of ordinary skill in the art is not apprised of the metes and bounds of the claimed invention.
Claim Rejections - 35 USC § 112 – Not further limiting
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 13 and 16 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 13 and Claim 16, which depend ultimately from Claim 7 and Claim 14, respectively, recite the compound of Formula I is "pilocarpine HCl". However, the claims from which they depend limits the compound of Formula I to a limited group of options that does not include "HCl". Therefore, the claims expand the compound of Formula I to include an additional option that is not encompassed by the claims from which Claim 13 and Claim 16 depend. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 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, 3-10, 13-16, and 18-20 are rejected under 35 U.S.C. 103 as being unpatentable over Andrade et al. (Experimental Eye Research (2014);120:1-9; cited in the 8/28/2023 IDS) in view of Tsifetaki et al. (Ann. Rheum. Dis. 2003; 62:1204–1207. doi: 10.1136/ard.2002.003889; cited in the 8/28/2023 IDS), Droy-Lefaix et al. (US PG-PUB 2003/0228299; cited in the 8/28/2023 IDS) and Paborji et al. (US PG-PUB 2014/0105976).
Claimed invention
Independent Claims 1, 7, and 14 are drawn to a composition comprising
a) a therapeutically effective amount of a compound of Formula I (e.g., pilocarpine salt) and
b) a therapeutically effective amount of lipoic acid.
Independent Claim 6 is drawn to a method of treating a patient with the pharmaceutical composition of Claim 1, wherein the effective dose of the compounds is in the range of about 0.01-100 mg/kg body weight/day.
Prior art
Andrade et al. studied the effects of alpha-lipoic acid on the dry eye model. In this study, alpha-lipoic acid treated animals exhibited an antioxidant activity in lacrimal gland and, at the same time, a pro-oxidant activity in corneal tissue. These differential effects resulted in improvement in dry eye and corneal epithelium and restoration of tear production. See p. 8, right column.
While Andrade teaches that alpha-lipoic acid was known to be useful for treating dry eye, Andrade does not expressly teach a pilocarpine agent as claimed (e.g., pilocarpine phosphoric acid).
However, it was known that alpha-lipoic acid can be combined with other active ingredients and further known that pilocarpine, like alpha-lipoic acid, is useful for ameliorating eye dryness. For example, Tsifetaki teaches that 10 mg daily pilocarpine administered to patients with Sjögren’s syndrome relieved symptoms of eye dryness. See p. 1206, right column. Droy-Lefaix teaches the use of an antioxidant for treating eye disorders. Droy-Lefaix mentions eye dryness as a disorder that can be treated by the invention and R-lipoic acid is an example of the antioxidant. See 0056-57, 0061-0066. The lipoic acid is preferably present in the drug at a concentration of 0.05 µg/ml to 200 µg/ml, preferably of 0.5 µg/ml to 5 µg/ml. See 0065. It has also been used in combination with numerous other active ingredients in oral compositions for its protective effects on the retina, in age-related degeneration, glaucoma and increased ocular pressure. See 0052.
Paborji teaches therapeutically acceptable forms of pilocarpine include salts that maintain the biological activity and properties of pilocarpine. Those salts include:
Acid salts:
phosphoric acid, methanesulfonic acid, salicylic acid, tartaric acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, tartaric acid, oxolic acid, acetic acid, formic acid, benzoic acid, and the like; and
Basic salts:
sodium, potassium, calcium, magnesium, dicyclohexylamine, N-methyl-D-glucamine, tris(hydroxymethyl)methylamine, arginine, lysine, and ammonium salts.
See 0011.
It would have been prima facie obvious to combine pilocarpine or a pharmaceutically acceptable salt (e.g., pilocarpine phosphoric acid salt or pilocarpine methanesulfonic acid salt) with R-lipoic acid in a composition (i.e., a physical mixture) because Andrade teaches that lipoic acid provided effective treatment of dry eye, Tsifetaki teaches that 10 mg daily pilocarpine administered to patients with Sjögren’s syndrome relieved symptoms of eye dryness while Droy-Lefaix also teaches that R-lipoic acid is useful for treating eye disorders, e.g., eye dryness, and that it can be combined with other active agents for eye disorders. The artisan would have had a reasonable expectation of success that the combination would be useful for treating dry eye. Generally, it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose (i.e., dry eye), in order to form a third composition to be used for the very same purpose; the idea of combining them flows logically from their having been individually taught in the prior art. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980): In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960). Conversely, there is no evidence in the record establishing the Applicant's combination of agents is any more effective or in any way different than any single member of that combination. See In re Dial, 140 USPQ 244 (C.C.P.A. 1964). In this case, both R-lipoic acid and pilocarpine, are described separately as being useful agents for treating dry eye symptoms. One of ordinary skill in the art would have found it obvious to combine R-lipoic acid and pilocarpine together to provide a composition for treating dry eye. The POSA would have further found it obvious to use a known derivative of pilocarpine such as pilocarpine phosphoric acid salt or pilocarpine methanesulfonic acid salt (Paborji) because it was known as a pharmaceutically useful form of pilocarpine for providing the therapeutic effects of pilocarpine. The artisan would have reasonably recognized it as a suitable pharmaceutical form of pilocarpine to provide pilocarpine’s effects to a subject.
Claims 3, 9, 10, 13, and 16 drawn to different modifications of lipoic acid:
Claims 3 defines lipoic acid with R-(+)-stereoisomerism and different substituents for the for RH. As outlined above, Droy-Lefaix teaches R-lipoic acid, i.e., R-(+)-lipoic acid. This teaching meets the limitations of:
Claim 9 (i.e., Formula IV, wherein RH is H),
Claim 10 (i.e., Formula IV, wherein RH is H) (in-part),
Claim 13 (in-part), and
Claim 16 (in-part).
Claims 10, 13, and 16 drawn to different modification of Formula I, i.e., pilocarpine:
Regarding Claim 10, which recite Formula I, as outlined above, the prior art suggests pilocarpine phosphoric acid and pilocarpine methanesulfonic acid.
While the recitation of “pilocarpine HCl” in Claim 13 (in-part) and Claim 16 (in-part) fails to further limit the claims from which they depend (see 35 USC § 112d rejection above), pilocarpine HCl is mentioned as a suitable therapeutic form of pilocarpine by Tsifetaki (see p. 1206, 2nd col, 1st full par.). Thus, a person of ordinary skill in the art (POSA) would have also found it obvious to use pilocarpine HCl because it was known as a suitable salt form for providing the therapeutic effects of pilocarpine.
Claims 4, 5, 8 and 15
Claims 4, 8 and 15 (in-part) recite the dose range of 0.1-200 mg of the pilocarpine agent. Tsifetaki teaches the use of 10 mg daily pilocarpine as outlined above.
Claim 5 and 15 (in-part) recite the dose range of 10 mg-2 g and 5 mg to 4 g of R-(+)-lipoic acid, respectively. Andrade teaches 180 mg/kg/day was administered to the animals. See p. 3, left column, 1st par. Thus, suggesting a composition containing 180 mg to provide the dose.
Claims 6 and 18
Claim 6 is drawn to treatment of a patient with the composition of claim 1,wherein the effective dose of the compounds is in the range of about 0.01 mg/kg body weight/day to about 100 mg/kg body weight/day. Each reference suggest treatment of eye disease as outlined above. Tsifetaki teaches pilocarpine treatment in patients with Sjögren’s syndrome usually starts with 5 mg at night for a few days, then 5mg twice daily (i.e., 10 mg), morning and night for a week, and then, if the patient does not respond, the dose is increased to 15 or 20 mg a day. This is done specifically to help avoid sweating and other side effects. In some cases (10%) the dose is increased to 30 mg a day. See Tsifetaki, p. 1206, 2nd col. Thus, for an average 70 kg human, the amounts disclosed are 0.07 mg/kg/day, 0.14 mg/kg/day, 0.21 mg/kg/day and 0.28 mg/kg/day. Thus, the amounts disclosed meet the claimed amount range of about 0.01-100 mg/kg body weight/day.
Regarding Claim 18, oral administration is described by Andrade and Tsifetaki. Andrade administered lipoic acid by diets formulated with fish oil and alpha-lipoic acid blended daily (Andrade, p. 3, section 2.2). Tsifetaki teaches patients taking oral pilocarpine had significant improvement in subjective global assessment of dry eyes (Tsifetaki, abstract).
Claims 19 and 20 drawn to intended uses
Claims 19 and 20 are drawn to compositions for the treatment of xerostomia, and burning mouth syndrome, for the treatment of xerostomia, and burning mouth syndrome and related conditions. However, these treatments are considered to be intended uses of the claimed composition that do not add patentable weight to the claim. Therefore, the prior art need not teach these intended uses to meet the limitations of the structure of the composition claimed.
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 1, 3-10, 13-16, and 18-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11,643,419 B2 (patent) in view of Tsifetaki et al. (Ann. Rheum. Dis. 2003; 62:1204–1207. doi: 10.1136/ard.2002.003889; cited in the 8/28/2023 IDS), Andrade et al. (Experimental Eye Research (2014);120:1-9; cited in the 8/28/2023 IDS), and Droy-Lefaix et al. (US PG-PUB 2003/0228299; cited in the 8/28/2023 IDS).
Claimed invention
Independent Claims 1, 7, and 14 are drawn to a composition comprising
a) a therapeutically effective amount of a compound of Formula I (e.g., pilocarpine salt) and
b) a therapeutically effective amount of lipoic acid.
Independent Claim 6 is drawn to a method of treating a patient with the pharmaceutical composition of Claim 1, wherein the effective dose of the compounds is in the range of about 0.01-100 mg/kg body weight/day.
Prior art
The patented claims read on a compound of Formula I (pilocarpine combined with adipic acid, cinnamic acid, dodecylsulfuric acid, galactaric acid, gentisic acid, glucuronic acid and more) or a stereoisomer thereof. A pharmaceutical composition containing the compound of Formula I that can be administered orally and can be used to treat xerostomia, dry mouth or dry mouth in Sjögren's syndrome.
While patented claims teach a compound of Formula I (pilocarpine combined with adipic acid, cinnamic acid, dodecylsulfuric acid, galactaric acid, gentisic acid, or glucuronic acid, etc.) or a stereoisomer thereof can be used in a pharmaceutical composition orally administrable and useful to treat xerostomia, dry mouth or dry mouth in Sjögren's syndrome, however, the patented claims do not teach the compound of formula V such as R-(+)-lipoic acid.
However, pilocarpine and lipoic acid were known to be useful for treating dry eye in patients with Sjögren’s syndrome. For example, Tsifetaki teaches that 10 mg daily pilocarpine administered to patients with Sjögren’s syndrome relieved symptoms of eye dryness. See p. 1206, right column. Additionally, Andrade et al. studied the effects of alpha-lipoic acid on the dry eye model. In this study, alpha-lipoic acid treated animals exhibited an antioxidant activity in lacrimal gland and, at the same time, a pro-oxidant activity in corneal tissue. These differential effects resulted in improvement in dry eye and corneal epithelium and restoration of tear production. See p. 8, right column. Droy-Lefaix teaches the use of an antioxidant for treating eye disorders. Droy-Lefaix mentions eye dryness as a disorder that can be treated by the invention and R-lipoic acid is an example of the antioxidant. See 0056-57, 0061-0066. The lipoic acid is preferably present in the drug at a concentration of 0.05 µg/ml to 200 µg/ml, preferably of 0.5 µg/ml to 5 µg/ml. See 0065. It has also been used in combination with numerous other active ingredients in oral compositions for its protective effects on the retina, in age-related degeneration, glaucoma and increased ocular pressure. See 0052.
It would have been prima facie obvious to combine a compound of Formula I (e.g., pilocarpine combined with adipic acid, cinnamic acid, dodecylsulfuric acid, galactaric acid, gentisic acid, or glucuronic acid) with R-lipoic acid in a composition (i.e., a physical mixture) because
a) the patented claims teach compounds of Formula I (pilocarpine combined with adipic acid, cinnamic acid, dodecylsulfuric acid, galactaric acid, gentisic acid, glucuronic acid, etc.) or a stereoisomer thereof can be used in pharmaceutical compositions for therapeutic use (e.g., treat Sjögren's syndrome),
b) Tsifetaki teaches that 10 mg daily pilocarpine administered to patients with Sjögren’s syndrome relieved symptoms of eye dryness
c) Andrade teaches that lipoic acid provided effective treatment of dry eye,
d) while Droy-Lefaix also teaches that R-lipoic acid is useful for treating eye disorders, e.g., eye dryness, and that it can be combined with other active agents for eye disorders.
The artisan would have had a reasonable expectation of success that the combination would be useful for treating dry eye. Generally, it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose (i.e., dry eye), in order to form a third composition to be used for the very same purpose; the idea of combining them flows logically from their having been individually taught in the prior art. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980): In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960). Conversely, there is no evidence in the record establishing the Applicant's combination of agents is any more effective or in any way different than any single member of that combination. See In re Dial, 140 USPQ 244 (C.C.P.A. 1964). In this case, both R-lipoic acid and pilocarpine, are described separately as being useful agents for treating dry eye symptoms. One of ordinary skill in the art would have found it obvious to combine R-lipoic acid and pilocarpine together to provide a composition for treating dry eye.
Claims 3, 9, 10, 13, and 16 drawn to different modifications of lipoic acid:
Claims 3 defines lipoic acid with R-(+)-stereoisomerism and different substituents for the for RH. As outlined above, Droy-Lefaix teaches R-lipoic acid, i.e., R-(+)-lipoic acid. This teaching meets the limitations of:
Claim 9 (i.e., Formula IV, wherein RH is H),
Claim 10 (i.e., Formula IV, wherein RH is H) (in-part),
Claim 13 (in-part), and
Claim 16 (in-part).
Claims 10, 13, and 16 drawn to different modification of Formula I, i.e., pilocarpine:
Regarding Claim 10, which recite Formula I, as outlined above, the prior art suggests compounds of Formula I such as pilocarpine combined with adipic acid, cinnamic acid, dodecylsulfuric acid, galactaric acid, gentisic acid, glucuronic acid, etc.
While the recitation of “pilocarpine HCl” in Claim 13 (in-part) and Claim 16 (in-part) fails to further limit the claims from which they depend (see 35 USC § 112d rejection above), pilocarpine HCl is mentioned as a suitable therapeutic form of pilocarpine by Tsifetaki (see p. 1206, 2nd col, 1st full par.). Thus, a person of ordinary skill in the art (POSA) would have also found it obvious to use pilocarpine HCl because it was known as a suitable salt form for providing the therapeutic effects of pilocarpine.
Claims 4, 5, 8 and 15
Claims 4, 8 and 15 (in-part) recite the dose range of 0.1-200 mg of the pilocarpine agent. Tsifetaki teaches the use of 10 mg daily pilocarpine as outlined above.
Claim 5 and 15 (in-part) recite the dose range of 10 mg-2 g and 5 mg to 4 g of R-(+)-lipoic acid, respectively. Andrade teaches 180 mg/kg/day was administered to the animals. See p. 3, left column, 1st par. Thus, suggesting a composition containing 180 mg to provide the dose.
Claims 6 and 18
Claim 6 is drawn to treatment of a patient with the composition of claim 1,wherein the effective dose of the compounds is in the range of about 0.01 mg/kg body weight/day to about 100 mg/kg body weight/day. Each reference suggest treatment of eye disease as outlined above. Tsifetaki teaches pilocarpine treatment in patients with Sjögren’s syndrome usually starts with 5 mg at night for a few days, then 5mg twice daily (i.e., 10 mg), morning and night for a week, and then, if the patient does not respond, the dose is increased to 15 or 20 mg a day. This is done specifically to help avoid sweating and other side effects. In some cases (10%) the dose is increased to 30 mg a day. See Tsifetaki, p. 1206, 2nd col. Thus, for an average 70 kg human, the amounts disclosed are 0.07 mg/kg/day, 0.14 mg/kg/day, 0.21 mg/kg/day and 0.28 mg/kg/day. Thus, the amounts disclosed meet the claimed amount range of about 0.01-100 mg/kg body weight/day.
Regarding Claim 18, oral administration is described by the patented claims, Andrade and Tsifetaki. Andrade administered lipoic acid by diets formulated with fish oil and alpha-lipoic acid blended daily (Andrade, p. 3, section 2.2). Tsifetaki teaches patients taking oral pilocarpine had significant improvement in subjective global assessment of dry eyes (Tsifetaki, abstract).
Claims 19 and 20 drawn to intended uses
Claims 19 and 20 are drawn to compositions for the treatment of xerostomia, and burning mouth syndrome, for the treatment of xerostomia, and burning mouth syndrome and related conditions. However, these treatments are considered to be intended uses of the claimed composition that do not add patentable weight to the claim. Therefore, the patented claims need not teach these intended uses to meet the limitations of the structure of the composition claimed. Notwithstanding this, the patented claims teach the compounds can be used to treat dry mouth.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRIS E SIMMONS whose telephone number is (571)272-9065. The examiner can normally be reached M-F: 9:30-6:00p.
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CHRIS E. SIMMONS
Examiner
Art Unit 1622
/CHRIS E SIMMONS/Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622