DETAILED ACTION
Election/Restriction
Restriction to one of the following inventions is required under 35 U.S.C. 121:
Group I Claims 1-7, drawn to a pharmaceutical formulation comprising 80 to 95 % (w/w) of nintedanib, or a pharmaceutically acceptable salt thereof, and 5 to 20 % (w/w) of poly polyvinyl alcohol (PVA), classified in A61K 31/496, A61K 47/10 A61K 9/00.
Group II Claims 8-12, drawn to a method for the preparation of the pharmaceutical formulation comprising 80 to 95 % (w/w) of nintedanib, or a pharmaceutically acceptable salt thereof, and 5 to 20 % (w/w) of poly polyvinyl alcohol (PVA), the method comprising the steps of a) preparing an aqueous PVA solution, and b) mixing the PVA solution with a powder of nintedanib, or a pharmaceutically acceptable salt thereof, classified in B01F 23/51, A61K 31/496, A61K 47/10.
Group III Claims 13-17, drawn to a method for the treatment of a back-of-the-eye disease in a patient in need thereof comprising administering to the eye of the patient a pharmaceutical formulation comprising 80 to 95 % (w/w) of nintedanib, or a pharmaceutically acceptable salt thereof, and 5 to 20 % (w/w) of poly polyvinyl alcohol (PVA), classified in A61P 27/02, A61K 31/496, A61K 47/10.
The inventions are independent or distinct, each from the other because:
Inventions I and II are related as process of making and product made. The inventions are distinct if either or both of the following can be shown: (1) that the process as claimed can be used to make another and materially different product or (2) that the product as claimed can be made by another and materially different process (MPEP § 806.05(f)). In the instant case the composition can be made by a different process such as forming a solution of nintedanib and adding PVA as a powder or a solution which is a different process from group II. .
Inventions I and III are related as product and process of use. The inventions can be shown to be distinct if either or both of the following can be shown: (1) the process for using the product as claimed can be practiced with another materially different product or (2) the product as claimed can be used in a materially different process of using that product. See MPEP § 806.05(h). In the instant case nintedanib can be used for conditions for the front of the eye like corneal neovascularization and for other areas like the lungs as is it a pharmaceutical composition (i.e. claim 1 does not expressly recite a site).
Inventions II and III are directed to related methods. The related inventions are distinct if: (1) the inventions as claimed are either not capable of use together or can have a materially different design, mode of operation, function, or effect; (2) the inventions do not overlap in scope, i.e., are mutually exclusive; and (3) the inventions as claimed are not obvious variants. See MPEP § 806.05(j). In the instant case, the inventions as claimed are to distinct as they are to materially different modes of operation and function/effect wherein they do not overlap in scope as Group II is to a method of making a composition comprising 80 to 95 % (w/w) of nintedanib, or a pharmaceutically acceptable salt thereof, and 5 to 20 % (w/w) of poly polyvinyl alcohol (PVA) but not to a method of use; whereas Group III is to a specific method of treatment of the back of the eye with a composition comprising 80 to 95 % (w/w) of nintedanib, or a pharmaceutically acceptable salt thereof, and 5 to 20 % (w/w) of poly polyvinyl alcohol (PVA) which is not related to and distinct from a method of making a product. Furthermore, the inventions as claimed do not encompass overlapping subject matter and there is nothing of record to show them to be obvious variants.
Restriction for examination purposes as indicated is proper because all the inventions listed in this action are independent or distinct for the reasons given above and there would be a serious search and/or examination burden if restriction were not required because one or more of the following reasons apply:
(a) the inventions have acquired a separate status in the art in view of their different classification;
(b) the inventions have acquired a separate status in the art due to their recognized divergent subject matter;
(c) the inventions require a different field of search (for example, searching different classes/subclasses or electronic resources, or employing different search queries);
Applicant is advised that the reply to this requirement to be complete must include (i) an election of an invention to be examined even though the requirement may be traversed (37 CFR 1.143) and (ii) identification of the claims encompassing the elected invention.
The election of an invention may be made with or without traverse. To reserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the restriction requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
If Applicant elects Group III, the following election of species applies:
This application contains claims directed to the following patentably distinct species of back-of-the-eye disease:
wet age-related macular degeneration (wAMD), dry macular degeneration, geographic atrophy, diabetic macular edema (DME), nonproliferative diabetic retinopathy (NPDR), cystoid macular edema (CME), choroidal neovascularization (CNV), retinal vein occlusion, and retinitis pigmentosa.
If Applicant elects the species genera of choroidal neovascularization (CNV), Applicant is to further elect a specific species disease condition from the species genera (i.e. wet AMD).
The species are independent or distinct because they have different symptoms and etiologies where the conditions are distinct. In addition, these species are not obvious variants of each other based on the current record.
Applicant is required under 35 U.S.C. 121 to elect a single disclosed species, for prosecution on the merits to which the claims shall be restricted if no generic claim is finally held to be allowable. Currently, claim 14 and 16 are generic.
There is a serious search and/or examination burden for the patentably distinct species as set forth above because at least the following reason(s) apply: The species are independent or distinct because they have different symptoms and etiologies (i.e. nonproliferative diabetic retinopathy requires the presence of diabetes but retinitis pigmentosa does not and is an inherited generic condition) where the conditions are distinct. In addition, these species are not obvious variants of each other based on the current record.
Applicant is advised that the reply to this requirement to be complete must include (i) an election of a species to be examined even though the requirement may be traversed (37 CFR 1.143) and (ii) identification of the claims encompassing the elected species, including any claims subsequently added. An argument that a claim is allowable or that all claims are generic is considered nonresponsive unless accompanied by an election.
The election may be made with or without traverse. To preserve a right to petition, the election must be made with traverse. If the reply does not distinctly and specifically point out supposed errors in the election of species requirement, the election shall be treated as an election without traverse. Traversal must be presented at the time of election in order to be considered timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are added after the election, applicant must indicate which of these claims are readable on the elected species.
Should applicant traverse on the ground that the species from which election is required, are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing them to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the species unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other species.
Upon the allowance of a generic claim, applicant will be entitled to consideration of claims to additional species which depend from or otherwise require all the limitations of an allowable generic claim as provided by 37 CFR 1.141.
During a telephone conversation with David Kershner on 08/18/2025 a provisional election was made without traverse to prosecute the invention of Group I, claims 1-7. Affirmation of this election must be made by applicant in replying to this Office action. Claims 8-17 str withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
The examiner has required restriction between product or apparatus claims and process claims. Where applicant elects claims directed to the product/apparatus, and all product/apparatus claims are subsequently found allowable, withdrawn process claims that include all the limitations of the allowable product/apparatus claims should be considered for rejoinder. All claims directed to a nonelected process invention must include all the limitations of an allowable product/apparatus claim for that process invention to be rejoined.
In the event of rejoinder, the requirement for restriction between the product/apparatus claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103 and 112. Until all claims to the elected product/apparatus are found allowable, an otherwise proper restriction requirement between product/apparatus claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowable product/apparatus claim will not be rejoined. See MPEP § 821.04. Additionally, in order for rejoinder to occur, applicant is advised that the process claims should be amended during prosecution to require the limitations of the product/apparatus claims. Failure to do so may result in no rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
Status of Application
Applicant has elected Group I in response to restriction requirement and for the examination.
Due to restriction, based on election of Group I, claims 8-17 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being drawn to a non-elected invention.
Claims 1-17 are pending.
Claims 1-7 are present for examination at this time.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
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.
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 7 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 7 recites the limitation " nintedanib esylate" in claim 5. There is insufficient antecedent basis for this limitation in the claim.
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.
Claims 1-3, 5-6 are rejected under 35 U.S.C. 103 as being unpatentable over Blizzard et al. (U.S. Pat. Pub. 2021/0308043).
Rejection:
Blizzard et al. teaches a sustained release biodegradable ocular implant comprising a hydrogel and at least about 150ug of a tyrosine kinase inhibitor like nintedanib (exemplified), which is dispersed within the hydrogel (abstract, claim 1, [130] Example 7 Table 28). The polymer for the implant includes polyvinyl alcohol (PVA) which also has a suitable glass transition temperature to lick in the molecular orientation for dry stretching [158, 206, 292, 380]. The implant can be an intravitreal implant [132]. The amount of tyrosine kinase inhibitor can also be in its salt forms [130] and is from about 15-about 80% (w/w) [186] and the polymer is about 15-about 80% [186]. The implant can be cylindrical/fiber with a diameter of about 0.1-about 0.5mm and a length of less than about 17mm (claim 1-2) with specific embodiments of implants with a length of about 6mm-about 10mm and a diameter of about 0.2-about 0.4mm [213] and additional embodiments of a diameter of about 0.2mm-about 0.3mm or about 0.3-about 0.4mm ([212], and lengths of about 6mm-about 8mm [214]. The amount of tyrosine kinase inhibitor in the implant is at least 150ug such as about 200ug-about 800ug including about 400ug, about 500ug, and about 600ug ([133], falling within the instant claimed range).
While Blizzard et al. does not exemplify the implant with nintedanib and polyvinyl alcohol, Blizzard et al. does exemplify nintedanib and does expressly teach the use of polyvinyl alcohol as the polymer wherein it would be prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to exemplify the express teaching of Blizzard et al. with a reasonable expectation of success. While Blizzard does not teach the exact claimed values for the amount of nintedanib and PVA and the length of the implant, they do overlap wherein even a slight overlap in ranges establishes a prima facie case of obviousness wherein it well within the skill of one of ordinary skill in the art to optimize within the range to arrive at the overlapping values as a means to attain the desired therapeutic profile with a reasonable expectation of success absent evidence of criticality for the claimed values.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Blizzard et al. (U.S. Pat. Pub. 2021/0308043) as applied to claims 1-3, 5-6 above, in view of Gaaz et al. (Properties and Applications of Polyvinyl Alcohol, Halloysite Nanotubes and Their Nanocomposites-2.Chemical Structure of PVA)
Rejection:
The teachings of Blizzard et al. are addressed above including that the ophthalmic/intravitreal hydrogel implant having a polymer like PVA.
Blizzard et al. does not expressly recite the level of hydrolyzation of the PVA but does teach the inclusion of PVA as the polymer in the hydrogel implant.
Gaaz et al. teaches that PVA is either partially hydrolyzed or fully hydrolyzed, where the hydrolysis levels are typical of 80% (partial) to reach more than 99% (full) and nearly fully hydrolyzed forms result in forming PVA hydrogel with tuneable properties (2.Chemical Structure of PVA- 1st paragraph - 2nd paragraph including Figure 1).
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the PVA as the fully hydrolyzed form as suggested by Gaaz et al. and produce the claimed invention; as PVA is known to be either partially hydrolyzed or fully hydrolyzed and it is prima facie obvious to incorporate the fully hydrolyzed forms as it is known to result in form PVA hydrogels with tuneable properties which is the field of endeavor of Blizzard et al. with a reasonable expectation of success.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Blizzard et al. (U.S. Pat. Pub. 2021/0308043) as applied to claims 1-3, 5-6 above, in view of Nguyen et al. (U.S. Pat. Pub.2017/0368061).
Rejection:
The teachings of Blizzard et al. are addressed above including that the ophthalmic/intravitreal implant having the tyrosine kinase inhibitor like nintedanib which can be a salt form in the implant in various amounts including about 400ug, about 500ug, and about 600ug ([133], falling within the instant claimed range).
Blizzard et al. does not expressly recite which nintedanib salt form but does teach the inclusion of nintedanib and that it can be in a salt form.
Nguyen et al. teaches that nintedanib is known to be in the salt form of nintedanib ethanesulfonate (also known as nintedanib esylate) and useful ophthlamically [39].
Wherein it would be obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to incorporate the nintedanib as nintedanib ethanesulfonate as suggested by Nguyen et al. and produce the claimed invention; as it is prima facie obvious to utilize the known ethanesulfonate salt form of nintedanib when Blizzard et al. teaches the inclusion of nintedanib salt forms with a reasonable expectation of success.
Conclusion
Claims 1-7 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GIGI GEORGIANA HUANG whose telephone number is (571)272-9073. The examiner can normally be reached Monday-Thursday 9:00-5:00pm.
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/GIGI G HUANG/Primary Examiner, Art Unit 1613