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 .
Claims
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.
Claim 31 is 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 31 recites ammonio methacrylate copolymer (Type). The claim is indefinite because the claims recites a broad limitation followed by a narrower limitation. It is not clear if (Type) is meant to further limit the copolymer.
Claim Rejections - 35 USC § 103 - Obviousness
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.
1) Claims 16-33 are rejected under 35 U.S.C. 103 as being unpatentable over Wirostko (US 2015/0157563) in view of Griesser et al. (Polymers, 2018).
Wirostko disclose an ocular composition comprising a polymer matrix and an antibiotic dispersed in the polymer matrix. The ocular composition may be formulated into an ocular insert, solution, film (meeting instant claim 17) or gel. The polymer matrix may comprise a thiolated hyaluronic acid (HA). The thiolated HA includes thiolated carboxymethyl hyaluronic acid cross-linked with a poly(ethylene glycol) diacrylates (interpreted as nonactivated). The hyaluronic active film comprises 10%, 12% and 16% of the film. Actives that are delivered by polymer matrix includes those that treat glaucoma. Glaucoma agents may be added to the compositions and include Latanoprost, Bimatopost, Travaprost, Timolol, Betaxalol, Dorzolamide, Brinzolamide, and Briminodine. The therapeutic agents comprise 0.01 to about 0.5% and 0.2% to about 10% of the composition. Additional ingredients can be added to the HA bioerodible polymer to improve a variety of polymeric properties such as mucoadhesiveness, flexibility, and the like. Non-limiting examples of such ingredients include methylcellulose, carboxymethylcellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, ethyl cellulose, hydroxyethylcellulose, hydroxypropyl cellulose, polyvinyl alcohol, polyvinyl-pyrrolidone, alginic acid, chitosan, xanthan gum, carrageenan, poly(acrylic) acid, or a derivative thereof (instant claim 31).
Wirostko differs from the instant claims insofar as it does not disclose the preactivated thiomer of hyaluronic acid or the nonactivated thiomers of hyaluronic acids of the instant claims.
Griesser et al. disclose thiolated hyaluronic acid as a versatile mucoadhesive polymer. Due the ability of disulfide bond formation within the polymer itself as well as with biological materials, certain properties such as mucoadhesive, gelling, enzyme inhibitory, permeation enhancing and release controlling properties are improved (Abstract).The composition may be used for drug delivery to the eye and used to treat ocular wounds. The hyaluronic acid is thiolated at the carboxyl group. The thiol group is further protected with 6-mercaptonicotinamide. Via this pre-activation with 6 mercaptonicotinamide the free thiol groups are oxidized to disulfide bonds. As free thiol groups from thiolated HA are sensitive towards oxidation and rapidly react with the cysteine-rich domains in the mucus, S-protection (pre-activation) plays a major role in the improvement of mucoadhesiveness, cohesiveness as well as stability against degradation. Thiolation of HA leads to an even 12-fold augmentation in mucoadhesion on buccal mucosa. Thiolated HA preactivated with 6-mercaptonicotinamide demonstrated a 4-fold improved adhesion time compared to thiolated HA. The unprotected polymers have a cysteine side chain (instant claim 23). The polymers are crosslinked (3.2). Crosslinking causes a higher stability.
It would have been obvious to one of ordinary skill in the art prior to filing the instant application to have use the pre-activated thiolated hyaluronic acids in conjunction with or as the thiolated hyaluronic acids of Wirostko motivated by the desire to produce a film with an improved mucoadhesiveness, cohesiveness as well as stability against degradation.
It would have been obvious to one of ordinary skill in the art prior to filing the instant application to have made the films of Wirostko with a combination of the activated and nonactivated thiolated hyaluronic acids of Griesser et al. motivated by the desire to obtain different mucoadhesiveness by combining polymers with different adhesive properties.
In regards to the amounts recited in claim 32, the preactivated thiomer of hyaluronic acid is a result effective variable because it controls that adhesiveness of the system that is applied to the eye. It would have taken no more than the relative skill of one of ordinary skill in the art to have adjusted the amount of preactivated thiomer of hyaluronic acid to obtain the desired therapeutic effect. See MPEP 2144.05.
In regards to claim 33, the composition of Wirostko may be used to deliver glaucoma actives either alone or in combination. Therefore, it would have been obvious to one of ordinary skill in the art prior to filing the instant application to have used the delivery systems of Wirostko modified with Griesser et al. to deliver the glaucoma drugs to treat glaucoma because they are suitable for delivering glaucoma therapeutic agents.
In regards to claims 18, the protection of the cysteine hyaluronic acid of Griesser et al. with 6-mercaptonicotinamide would yield one of the compounds of instant claim 18.
In regard to instant claim 20, the moles of 6-mercaptonicotinamide would control how much of the hyaluronic acid is protected, making it a result effective variable. It would have been in the relative skill of one of ordinary skill in the art to have adjusted the micromole/g of 6-mercaptonicotinamide in order to arrive at the desired substitution on the hyaluronic acid. See MPEP 2144.05.
1) Claims 16-22 and 24-33 are rejected under 35 U.S.C. 103 as being unpatentable over Wirostko (US 2015/0157563) in view of Nowak et al. (Inter. J. of Pharm., 2015).
Wirostko disclose an ocular composition comprising a polymer matrix and an antibiotic dispersed in the polymer matrix. The ocular composition may be formulated into an ocular insert, solution, film (meeting instant claim 17) or gel. The polymer matrix may comprise a thiolated hyaluronic acid (HA). The thiolated HA includes thiolated carboxymethyl hyaluronic acid cross-linked with a poly(ethylene glycol) diacrylates (interpreted as nonactivated). The hyaluronic active film comprises 10%, 12% and 16% of the film. Actives that are delivered by polymer matrix includes those that treat glaucoma. Glaucoma agents may be added to the compositions and include Latanoprost, Bimatopost, Travaprost, Timolol, Betaxalol, Dorzolamide, Brinzolamide, and Briminodine. The therapeutic agents comprise 0.01 to about 0.5% and 0.2% to about 10% of the composition. Additional ingredients can be added to the HA bioerodible polymer to improve a variety of polymeric properties such as mucoadhesiveness, flexibility, and the like. Non-limiting examples of such ingredients include methylcellulose, carboxymethylcellulose, hydroxypropyl methylcellulose, hydroxyethyl cellulose, ethyl cellulose, hydroxyethylcellulose, hydroxypropyl cellulose, polyvinyl alcohol, polyvinyl-pyrrolidone, alginic acid, chitosan, xanthan gum, carrageenan, poly(acrylic) acid, or a derivative thereof (instant claim 31).
Wirostko differs from the instant claims insofar as it does not disclose the preactivated thiomer of hyaluronic acid or the nonactivated thiomers of hyaluronic acids of the instant claims.
Nowak et al. disclose preactivated hyaluronic acid as a potential mucoadhesive. Mucoadhesive polymeric excipients were developed for vaginal drug delivery systems. Hyaluronic acid (HA) was thiolated and subsequently preactivated with 6-mercaptonicotinamide (HA-CYS–MNA) (encompassing 6-mercaptonicotinamide cysteine, instant claim 18) to enhance stability and mucoadhesive properties on vaginal mucosa. Modifying HA-CYS with MNA resulted in higher stability (3.6-fold prolonged disintegration time compared to unmodified hyaluronic acid) and prolonged mucoadhesion time (Abstract). The thiol and disulfide were present exhibiting 218.87 micromole per game of HA and 173.8 micromole per gram respectively (3.1).
Although Nowak et al. disclose virginal mucosa, this can be translated to develop delivery of therapeutics to the mucosa of the eye. Therefore, it would have been obvious to one of ordinary skill in the art prior to filing the instant application to have used the pre-activated thiolated hyaluronic acids in conjunction with or as the thiolated hyaluronic acids of Wirostko motivated by the desire to produce a film with higher stability.
In regards to the amounts of in claim 32, the preactivated thiomer of hyaluronic acid is a result effective variable because it controls the stability and the adhesiveness of the system that is applied to the eye. It would have taken no more than the relative skill of one of ordinary skill in the art to have adjusted the amount of preactivated HA in order to obtain the desire stability and residence time for delivery of the active to the eye. See MPEP 2144.05.
In regards to claim 33, the composition of Wirostko may be used to deliver glaucoma actives either alone or in combination. Therefore, it would have been obvious to one of ordinary skill in the art prior to filing the instant application to have used the delivery systems of Wirostko modified with the preactivated HA of Nowak et al. to deliver the glaucoma drugs to treat glaucoma because they are suitable for delivering glaucoma therapeutic agents.
In regard to instant claim 20, the moles of 6-mercaptonicotinamide would control how much of the hyaluronic acid is substituted with the 6-mercaptonicotinamide, making it a result effective variable. It would have been in the relative skill of one of ordinary skill in the art to have adjusted the micromole/g of 6-mercaptonicotinamide in order to arrive at the desired substitution on the hyaluronic acid. See MPEP 2144.05.
Obvious-Type 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 16-33 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13-31 of copending Application No. 17/796,183 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims are coextensive insofar as they both recite a mucoadhesive delivery system comprising a preactivated thiomer polymer. The instant claims differ from the copending claims insofar as they recite hyaluronic acid as the polymer. However the copending claims recite that hyaluronic acid may be the polymer in dependent claim 15. Therefore the instant claims are obvious over the copending claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 16-33 are rejected.
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LEZAH ROBERTS whose telephone number is (571)272-1071. The examiner can normally be reached Monday-Friday 11:00-7:30.
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/LEZAH ROBERTS/ Primary Examiner, Art Unit 1612
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