DETAILED ACTION
The receipt is acknowledged of applicant’s election filed 12/10/2025.
Claims 1-21 previously presented and currently pending.
Claims 1-16, 19-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 08/18/2025.
Claims 17, 18 and 21 are subject of this office action.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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 .
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 17, 18 and 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 10,736,885 in view of Shailubhai (US 2019/0134044, IDS filed 05/10/2024). The issued claims and the pending claim in this application are directed to a common subject matter as follows: a method of treating dermatological disorder by topically administering composition comprising an pharmaceutically acceptable vehicle and at least one multi-target inhibitor including axitinib. Topical administration as currently claimed is claimed by claim 3 of the issued patent. The instantly claimed drugs are claimed by claims 4, 6, 7 of the issued patent. Treating dermatological condition and wound are claimed by claim 1 and 13 of the issued patent. The difference between the instant claims and the issued claims is that the issued claims do not recite the composition is an aqueous suspension Shailubhai teaches composition comprising kinase inhibitor (abstract; ¶¶ 0008, 0009, 0064, 0070, 0170, 0287; claim 1). The composition is a topical aqueous suspension (¶¶ 0197, 0218, 0229). Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the present invention to treat skin wound by composition comprising multi-target inhibitor as claimed by the issued claims, and use aqueous suspension taught by Shailubhai. One would have been motivated to do so because Shailubhai teaches suitability for treating skin conditions by an aqueous suspension comprising multi-target inhibitor. One would reasonably achieved the present claims.
Claims 17, 18, 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 12,138,252 in view of Shailubhai (US 2019/0134044). The issued claims and the pending claim in this application are directed to a common subject matter as follows: a method of treating dermatological disorder by topically administering composition comprising an pharmaceutically acceptable vehicle and at least one multi-target inhibitor including axitinib. Topical administration as currently claimed is claimed by claims 8-15 of the issued patent. The instantly claimed drugs are claimed by claims 1-4, of the issued patent. Treating dermatological conditions are claimed by the issued patent, and inherently will encompass wound. The teachings of Shailubhai are discussed above. Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the present invention to treat dermatological condition by composition comprising multi-target inhibitor as claimed by the issued claims, and use aqueous suspension taught by Shailubhai. One would have been motivated to do so because Shailubhai teaches suitability for treating skin conditions by an aqueous suspension comprising multi-target inhibitor. One would reasonably achieved the present claims.
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 17, 18 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Shailubhai (US 2019/0134044) by itself or combined with Pojasek et al. (US 2010/0278784) both references are provided by IDS filed 05/10/2024.
Applicant Claims
Claim 17 is directed to a method of treating a dermatological disorder, an ophthalmologic disorder, or a urogenitary disorder, comprising: locally administering an effective amount of the pharmaceutical composition to treat a subject suffering from the dermatological disorder, the ophthalmologic disorder, or the urogenitary disorder, wherein the pharmaceutical composition comprises an aqueous suspension comprising a pharmaceutically acceptable vehicle and at least one multi-target inhibitor, wherein the at least one multi-target inhibitor is at least one of axitinib, nintedanib, sorafenib, and lenvatinib.
Claim 18 recites that the method of claim 17, wherein the subject suffers from the dermatological disorder.
Claim 21 is directed to a method of treating a wound, comprising: locally administering an effective amount of the pharmaceutical composition to treat a subject suffering from a wound, wherein the pharmaceutical composition comprises an aqueous suspension comprising a pharmaceutically acceptable vehicle and at least one multi-target inhibitor, wherein the at least one multi-target inhibitor is at least one of axitinib, nintedanib, sorafenib, and lenvatinib.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Shailubhai teaches treating skin cancer and treating wound using composition comprising a carrier and multi-target kinase inhibitor, e.g. axitinib, nintedanib, lenvatinib, regorafenib, sunitinib (abstract; ¶¶ 0008, 0009, 0064, 0070, 0125-0137, 0170, 0211, 0287; example 5; claim 1). The composition can be an aqueous suspension (¶¶ 0197, 0218, 0229). The composition can be administered topically in form of aqueous suspension (¶ 0218).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.012)
Finding of Prima Facie Obviousness Rational and Motivation
(MPEP §2142-2143)
While the reference teaches all the elements of the claims, however, the reference does not teach a single embodiment with aqueous suspension to treat dermatological condition (claims 17-18) or to treat wound (claim 21). As such, the instant prior art does not appear to provide sufficient specificity, i.e., involves some “picking and choosing” to give rise to anticipation. See, Corning Glass Works v. Sumitomo Elec., 868 F.2d 1251, 1262 (Fed. Circ. 1989). That being said, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect.... the combination is obvious”. KSRv. Teleflex, 127 S,Ct. 1727, 1740 (2007)(quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). Consistent with this reasoning, it would have obvious to have selected the various combinations of features claimed from within the prior art disclosure, specifically treating dermatological condition using aqueous suspension comprising carrier and multi target inhibitors because it is suitable for many formulations, e.g. topical.
Pojasek teaches method for treating skin conditions, e.g. skin wrinkles, acne, wounds and scar using composition comprising a carrier, and the active agents multi-target inhibitor, e.g. axitinib, sorafenib and E 7080 that is Lenvatinib. The composition can be aqueous suspension that is administered topically (abstract; ¶¶ 0016-0020, 0028-0038, 0049, 0069, 0148, 0152, 0155, 0158, 0162-0164, 0170, 0174, 0179, 0184, 0192-0196, 0223).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the present invention to successfully treat dermatological conditions including skin cancer (claims 17-18) and wound (claim 20) using aqueous suspension comprising multi-target inhibitors, e.g. axitinib, nintedanib, sorafenib, or Lenvatinib as taught by Shailubhai.
Optionally, further, it would have been obvious to one having ordinary skill in the art before the effective filing date of the present invention to treat dermatological conditions (elected species including wound) as taught by Shailubhai, and successfully use axitinib, nintedanib, sorafenib, or lenvatinib in a topical an aqueous suspension as taught by Pojasek. One would have been motivated to do so because Pojasek teaches treating of skin conditions, e.g. skin wrinkles, acne, wounds and scar using composition comprising a carrier, and the active agents multi-target inhibitor, e.g. axitinib, sorafenib and lenvatinib can be successfully treated by aqueous suspension comprising such agents and administered topically. One would reasonably expected treating skin conditions using the claimed agents in an aqueous suspension administered topically.
Absent any evidence to the contrary, and based upon the teachings of the prior art, there would have been a reasonable expectation of success in practicing the instantly claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the present invention.
Response to Arguments
Applicant's arguments filed 12/10/2025 have been fully considered but they are not persuasive.
Response to Rejections of Claims 17-18 and 21 for Double Patenting
Applicants argue that Shailubhai is silent as to the use of an aqueous suspension for local administration of a multi-target inhibitor, especially for at least one of axitinib, nintedanib, sorafenib, and lenvatinib, as presently claimed. Paragraphs 197, 218 and 229 of Shailubhai cited by the Office Action is silent as to local administration, and mentions aqueous and non-aqueous solutions, suspensions, and emulsions without designating what active agent should be used for a given formulation type, or what type of tissue a given formulation type should be used for, and provides list of active agents to be formulated with miciclib.
In response to this argument, it is argued that Shailubhai is not silent to the use of aqueous suspension for local administration. The reference is relied upon in the double patenting rejection for solely teaching the aqueous solution. The currently claimed topical or local application is claimed by both issued patent and the currently claimed drugs are claimed by both issued patents, as set forth in this office action, and no need to be taught by Shailubhai.
Note the comprising language of the claims permits the use of any additional agents, active or inactive, even in major amounts.
Applicants argue that one of ordinary skill in the art would not have had any reason from Shailubhai to specifically choose an aqueous suspension for local administration of the currently claimed specific multi-target inhibitors, given the vast amount of formulation choices in Shailubhai, and would not have had any reason from Shailubhai, or reasonable expectation of success, to specifically choose the claimed active agents from the extensive list disclosed by Shailubhai for potential combination with miciclib; and then specifically choose a dermatological disorder, an ophthalmologic disorder, or a urogenitary disorder from the extensive list of cancers disclosed by Shailubhai.
In response to this argument, it is argued that the claimed drugs and conditions to be treated are claimed by the issued patents. Regarding the aqueous formulation, it is argued that It had been decided by Courts that the indiscriminate selection of "some" from among "many" is considered prima facie obvious. In re Lemin, 141 USPQ 814 (1964); National Distillers and Chem. Corp. V. Brenner, 156 USPQ 163. One having ordinary skill in the art would have selected aqueous suspension from the different formulation taught by the reference that are not too many. Further. One would have selected dermatological condition to be treated and the specific drug based on suitability of multitarget inhibitor to treat such condition. The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945). “Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle.” 325 U.S. at 335, 65 USPQ at 301. See also In re Leshin, 227 F.2d 197, 125 USPQ 416 (CCPA 1960); Ryco, Inc. v. Ag-Bag Corp., 857 F.2d 1418, 8 USPQ2d 1323 (Fed. Cir. 1988).
Claim Rejections Under 35 U.S.C. §103
Regarding Shailubhai reference, applicants argue that Shailubhai is silent as to the use of an aqueous suspension for local administration of a multi-target inhibitor, especially for at least one of axitinib, nintedanib, sorafenib, and lenvatinib, as presently claimed. For example, paragraph 197 of Shailubhai cited by the Office Action is silent as to local administration. Additionally, paragraph 197 mentions aqueous and non-aqueous solutions, suspensions, and emulsions without designating what active agent should be used for a given formulation type, or what type of tissue a given formulation type should be used for. Shailubhai is drawn to treating cancer with miciclib and discloses an extensive list of active agents that can be combined with miciclib for treating cancer; claim 1 and paragraph 9. Paragraph 197 of Shailubhai provides no guidance as to which of those active agents should be formulated with miciclib in an aqueous VS. non-aqueous formulation or in a solution vs. a suspension VS. an emulsion, and for what type of tissue.
In response to this argument, it is argued that the reference clearly teaches formulation as an aqueous suspension, and not silent, and such formulation would contain all the drugs and ingredients of the formulation including multi-target inhibitors. In paragraph [0218] of the reference, Shailubhai suggests topical delivery using formulation suitable for such a route. One having ordinary skill in the art would have determined the suitable formulation for topical administration from those formulations taught by the references, including aqueous formulation. If the reference was to describe topical aqueous suspension to particularly deliver multi-target inhibitors, the reference would have been considered for anticipation.
Regarding the argument that the reference teaches various formulations, e.g. aqueous, non-aqueous, emulsion, etc., it had been decided by Courts that the indiscriminate selection of "some" from among "many" is considered prima facie obvious. In re Lemin, 141 USPQ 814 (1964); National Distillers and Chem. Corp. V. Brenner, 156 USPQ 163. Further, the selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945). “Reading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle.” 325 U.S. at 335, 65 USPQ at 301. See also In re Leshin, 227 F.2d 197, 125 USPQ 416 (CCPA 1960); Ryco, Inc. v. Ag-Bag Corp., 857 F.2d 1418, 8 USPQ2d 1323 (Fed. Cir. 1988).
Regarding the argument that the reference formulation must be formulated with miciclib, it is argued that the expression “comprising” of the claims’ language permits the presence of other ingredients, active or inactive, even in major amounts.
Applicants argue that paragraph 218 cited by the Office Action is silent as to local administration. Additionally, paragraph 218 mentions aqueous and non-aqueous solutions and suspensions without designating what active agents are used for any given formulation type. Paragraph 218 of Shailubhai also provides no guidance as to which of the extensive list of active agents should be formulated with miciclib in an aqueous VS. non-aqueous formulation or in a solution VS. a suspension, and for what type of tissue. Similarly, paragraph 229 cited by the Office Action is silent as to local administration. Additionally, paragraph 229 mentions both aqueous solutions and dispersions, without designating what active agents are used for any given formulation type. Paragraph 229 of Shailubhai also provides no guidance as to which of the extensive list of active agents should be formulated with miciclib in an aqueous solution or dispersion, and for what type of tissue.
In response to this argument, it is argued that paragraph [0218] clearly suggests aqueous suspension and topical administration. This paragraph referring to the all formulations that would comprise the drugs and any other ingredients. The teaching of the reference would suggests to one having ordinary skill in the art to use the taught multi-target inhibitors in the topical aqueous suspension. Note that the “comprising” language of claims permits the presence of miciclib, and any other drug or additional ingredients, active or inactive, even in major amounts. As applicants themselves admit, the reference teaches aqueous suspension, along with others, and the use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain. In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir 1983). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments.
Applicants argue that Shailubhai largely relies on systemic administration rather than local administration (see, e.g., paragraphs 213, 233, and Example 7), and teaches that capsules and tablets are preferred (paragraphs 190 and 191). Thus, Shailubhai would have led one of ordinary skill in the art away from using an aqueous suspension for locally administering the presently claimed compounds.
In response to this argument, it is argued that one having ordinary skill in the art would have drawn from the teaching of the reference that the claimed multi-target inhibitors can be administered topically from an aqueous suspension formulation to treat dermatological conditions. No teaching in the reference would deter one skilled in the art from doing so. "A reference may be said to teach away when a person of ordinary skill, upon reading the reference, would be discouraged from following the path set out in the reference, or would be led in a direction divergent from the path that was taken by the applicant. The degree of teaching away will of course depend on the particular facts; in general, a reference will teach away if it suggests that the line of development flowing from the reference's disclosure is unlikely to be productive of the result sought by the applicant." In re Gurley, 27 F.3d 551,553 (Fed. Cir. 1994). The reference here is not teaching any drawbacks from topical application of aqueous suspension of the claimed drugs, so can be used as suggested by the reference.
Applicants argue that one of ordinary skill in the art would not have had any reason from Shailubhai to choose an aqueous suspension for local administration of the currently claimed active agents for a dermatological disorder, an ophthalmologic disorder, or a urogenitary disorder, given the vast amount of formulation choices in Shailubhai, the extensive list of active agents disclosed by Shailubhai, and the cancer types to treat disclosed by Shailubhai. One of ordinary skill would not have had any reason from Shailubhai, or reasonable expectation of success, to choose a particular drug, for choosing a particular formulation type, or for a choosing a particular type of tissue to treat. One of ordinary skill in the art would not have arrived at the claimed subject matter from the overwhelming number of potential combinations and the lack of guidance of Shailubhai.
In response to this argument, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In this case, there is motivation to modify the reference and use aqueous suspension topically to treat dermatological conditions based on suitability of these elements to treat skin conditions, note claim 17 is very broad in terms of the elected dermatological condition. It should be noted that the motivation to combine/modify references can be different from the ones set forth by Applicant. That is, as long as motivation exists to combine the elements, the problem to be solved does not have to involve the same reason. As such, the examiner respectfully submits that there is motivation to combine or modify the cited references as set forth in this office action.
Regarding the reasonable expectation of success, it is argued that obviousness does not require absolute predictability of success all that is required is a reasonable expectation of success. See In re Kubin, 561 F.3d at 1360. The Court has held that "the test of obviousness is not express suggestion of the claimed invention in any or all of the references but rather what the references taken collectively would suggest to those of ordinary skill in the art presumed to be familiar with them." See In re Rosselet, 146 USPQ 183, 186 (CCPA 1965). "There is no requirement (under 35 USC 103(a)) that the prior art contain an express suggestion to combine known elements to achieve the claimed invention. Rather, the suggestion to combine may come from the prior art, as filtered through the knowledge of one skilled in the art." Motorola, Inc. v. Interdigital Tech. Corp., 43 USPQ2d 1481, 1489 (Fed. Cir.1997). An obviousness determination is not the result of a rigid formula disassociated from the consideration of the facts of a case. Indeed, the common sense of those skilled in the art demonstrates why some combinations would have been obvious where others would not. See KSR Int'l Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007) ("The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.").
Applicants argue that the Office Action makes the finding of obviousness based merely on Shailubhai allegedly disclosing genera that contain the presently claimed active agents and aqueous formulation. Applicants argue that the analysis in the Office Action is incorrect. The fact that a claimed species or subgenus is encompassed by a prior art genus is not sufficient by itself to establish a prima facie case of obviousness. In re Baird, 16 F.3d 380, 382, 29 USPQ2d 1550, 1552 (Fed. Cir. 1994)." See MPEP 2144.087. Shailubhai does not teach the specific claimed method, as Shailubhai does not specifically teach local administration of the claimed active agents for the claimed disorders using aqueous suspensions. One of ordinary skill would have had no reason to choose a method of locally administering the presently claimed active agents for the presently claimed disorders using an aqueous suspension formulation from reading Shailubhai.
In response to this argument, it is repeated that the use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain. In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir 1983). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. The reference does not teach the claimed species with sufficient specificity, however, suggests the claimed species and made them obvious. In addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742. A person of ordinary skill in the art who is not an automaton is capable of producing the composition of the instant claims with predictable successful results.
Applicants argue that Shailubhai's specific teaching is for in vivo administration (see Example 7) of a combination of miciclib and sorafenib (which is not currently claimed). Shailubhai does not otherwise teach what formulation type to use for any of the extensive list of active agents disclosed in paragraph 9, or for any of the types of cancers disclosed in various tissues.
In response to this argument, it is repeated that the reference is relied upon for all the teachings, not only the examples, even nonpreferred embodiment. The reference teaches the claimed drugs to use in dermatological conditions and wound treating, and teaches aqueous suspension. The claims language permits other ingredients in the composition. The reference teaches treating wound in paragraph [0211], not only treating cancer.
Applicants argue that in Example 4 of the present application, local administration to the eye by intravitreal injection of aqueous suspensions of nintedanib or lenvatinib in rabbits resulted in 4-7% and 3-9% of the dose remaining, respectively, in the vitreous humor even at 42 days after administration. For lenvatinib, 9-17% of the intravitreal dose remained in the vitreous humor at day 29 after administration of an aqueous suspension. Both lenvatinib and nintedanib showed very high tissue concentrations in eye tissues at days 29 and 42 post-dosing with the aqueous suspension, higher than 1 µg per gram of tissue. These unexpectedly prolonged tissue exposures would not be possible based on the systemic half-lives and clearance rates of these active ingredients. For example, the terminal plasma half-life in man is 2-5 hours for axitinib, 9.5 hours for nintedanib, 30 hours for lenvatinib, and 28 hours for regorafenib (see Example 2, paragraph 557 of the present application). Similarly, in Example 8 of the present application, local administration to urogenital tissue by intraprostatic injection of aqueous suspensions ofaxitinib, sorafenib, pirfenidone, and riociguat in rats resulted in high drug levels ofaxitinib, sorafenib, and riociguat in prostate tissue at 2 weeks after the last injection.
In response to this argument, it is noted that this argument is against the nonelected species of ophthalmological and urological disorders that do not commensurate in scope with the elected species of dermatological disorder.
Applicants argue that in Example 7 of the present application, local administration to the skin by intradermal injection of aqueous suspensions of axitinib and nintedanib in the dorsum of minipigs resulted in significant drug concentrations at the local injection site over 28 days after injection. Such unexpectedly prolonged tissue exposure would not have been possible from systemic administration. In Example 10, local administration of aqueous suspensions of axitinib, nintedanib, sorafenib, or lenvatinib around dermal wounds in minipigs resulted in delayed granulation tissue formation and prolonged presence of myofibroblasts compared to vehicle-treated control wounds, supporting enhanced wound healing. Similarly, administration to prostate.
In response to this argument, it is argued that the reference teaches the claimed drugs in an aqueous suspension and administered topically as claimed. Therefore any property applicants achieved would be expected from the prior art formulation, absent evidence to the contrary. In addition, regarding applicant's arguments of unexpected superior results in the instant specification, it is the examiner's position that the data in the specification regarding prolonged tissue exposure are not unexpected results and therefore cannot rebut prima facie obviousness. It is obvious that applying topical drug to topical lesion, e.g. skin wound, would provide prolonged exposure of the lesion to the drug than if the drug administered systemically and reaching the topical lesion via systemic circulation. The examiner directs applicant's attention to MPEP 716.02 (a). "A greater than expected result is an evidentiary factor pertinent to the legal conclusion of obviousness...of the claims at issue." In re Corkill, 711 F.2d 1496, 266 USPQ 1006 (Fed.Cir. 1985). In Corkhill, the claimed combination showed an additive result when a diminished result would have been expected. Furthermore, the MPEP states, "Expected beneficial results are evidence of obviousness of a claimed invention, just as unexpected results are evidence of unobviousness thereof." In re Gershon, 372 F.2d 535, 538, 152 USPQ 602, 604 (CCPA 1967). Argument regarding administration to the prostate are not directed to the elected species.
Regarding Pojasek reference, applicants argue that only paragraphs 170 and 174 of the reference mention suspension formulations. Paragraph 170 mentions an extensive list of formulation types: without indicating any preference for a particular type of formulation. Similarly, paragraph 174 also mentions many formulation types without indicating any preference for a particular type of formulation. Paragraph 174 is drawn to controlled/extended release, following from disclosure of controlled/extended release in paragraph 173; and paragraph 173 describes "preferable oral compositions," which if anything would have led one of ordinary skill in the art away from using a suspension of paragraph 174 for local administration to treat a skin condition described by Pojasek.
In response to this argument, it is argued that Pojasek is directed to treating skin conditions including wounds using topical composition, and suggested aqueous suspension. The teachings of the reference would have suggested the claimed invention to one having ordinary skill in the art.
Applicants argue that Pojasek only discloses at paragraph 164 an extensive "laundry list" of active agents. Pojasek does not mention nintedanib or lenvatinib at all. None of the other paragraphs cited by the Office Action mentions axitinib or sorafenib, or gives any guidance to pick and choose any particular active agent for any particular formulation type among the extensive lists of active agents and formulation types described. One of ordinary skill in the art would not have had any reason from Pojasek to specifically choose an aqueous suspension for local administration of axitinib, nintedanib, sorafenib, or lenvatinib for a dermatological disorder,
In response to this argument, unlike applicants assertion, it is argued that the reference clearly teaches lenvatinib that is E 7080 that is Lenvatinib. The reference further teaches axitinib and sorafenib that are claimed. Note the claims do not require all the claimed drugs, only one. It is further argued that the reference is relied upon for all it suggests to one versed in the art. It had been decided by Courts that the indiscriminate selection of "some" from among "many" is considered prima facie obvious. In re Lemin, 141 USPQ 814 (1964); National Distillers and Chem. Corp. V. Brenner, 156 USPQ 163.
Applicants repeat the argument regarding the genus/species situation and unexpected results in the specification as for Shailubhai. Therefore, the position taken by the examiner is hereby reiterated.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/ISIS A GHALI/Primary Examiner, Art Unit 1611 /I.G./