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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/15/25 has been entered.
Status of the claims
Claim 53 has been cancelled.
Claims 52, 54-59,61-64,66-68 and 70-73 are currently under examination.
All rejections not reiterated have been withdrawn.
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 52, 54-59,61-64,66-68 and 70-73 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 73-84 of copending Application No. 17471777 in view of Weinstein et al. (US 4,753,958, Published June 28, 1988).
Inter alia the claims of ‘777 application embrace a topical pharmaceutical composition comprising porfimer sodium, one or more gelling agents, polysorbate 80, glycerin, benzyl alcohol, phenoxyethanol, and hexylene glycol. The composition comprises a photosensitizer, one or more permeation enhancers, a humectant, a solubilizer, and a preservative. The porfimer sodium is about 0.5% w/w. The composition further comprises one or more permeation enhancer ranging from about 0.5% to about 50% w/w, and wherein the gelling agent is hydroxy propyl cellulose. One or more penetration enhancers is about 0.5% to about 50 % w/w, the polysorbate 80 is about 1 % to about 3 % w/w, glycerin is about 10 % to about 20 % w/w, benzyl alcohol is about 1 % to about 3 % w/w, phenoxyethanol is about 0.5 % to about 2 % w/w, hexylene glycol is about 0.5 % to about 2 % w/w, and hydroxy propyl cellulose is about 0.5 % to about 2 % w/w in the pharmaceutical composition. Furthermore, the composition additionally comprises potassium iodide (KI), wherein the KI is about 1% w/w to about 2% w/w in the composition. The composition comprises one or more permeation enhancers selected from the group consisting of propylene glycol, polyethylene glycol 400 SR, polyethylene glycol 300 LA, diethylene glycol monoethyl ether, DMSO, Polysorbate 80 SR. Lastly, the permeation enhancer comprises DMSO and the DMSO is about 40% w/w in the composition.
The claims do not recite a method of administering a pharmaceutical composition comprising porfimer sodium to sun exposed skin, however Weinstein teaches applying a composition comprising porfimer sodium to skin followed by light application. It would have been prima facie obvious to use the composition of the ‘777 claims in the method of Weinstein because one would have recognized it as obvious. See MPEP 2144.07.
Claims 52, 54-59,61-64,66-68 and 70-73 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 85-93 of copending Application No. 1741777 as evidence by PennMedicine (PennMedicine, MRSA Infections (methicillin-resistant staphylococcus aureus); available online from at least: November 6, 2020)
Inter alia the claims of ‘777 application embraces a method of applying the composition to a patient wherein the composition comprises a topical pharmaceutical composition comprising porfimer sodium, one or more gelling agents polysorbate 80, glycerin, benzyl alcohol, phenoxyethanol, and hexylene glycol. The composition comprises a photosensitizer, one or more permeation enhancers, a humectant, a solubilizer, and a preservative. The porfimer sodium is about 0.5% w/w. The composition further comprises one or more permeation enhancer ranging from about 0.5% to about 50% w/w, and wherein the gelling agent is hydroxy propyl cellulose. One or more penetration enhancers is about 0.5% to about 50 % w/w, the polysorbate 80 is about 1 % to about 3 % w/w, glycerin is about 10 % to about 20 % w/w, benzyl alcohol is about 1 % to about 3 % w/w, phenoxyethanol is about 0.5 % to about 2 % w/w, hexylene glycol is about 0.5 % to about 2 % w/w, and hydroxy propyl cellulose is about 0.5 % to about 2 % w/w in the pharmaceutical composition. Furthermore, the composition additionally comprises potassium iodide (KI), wherein the KI is about 1% w/w to about 2% w/w in the composition. The composition comprises one or more permeation enhancers selected from the group consisting of propylene glycol, polyethylene glycol 400 SR, polyethylene glycol 300 LA, diethylene glycol monoethyl ether, DMSO, Polysorbate 80 SR. Lastly, the permeation enhancer comprises DMSO and the DMSO is about 40% w/w in the composition.
The method of the ‘777 application is a method of treating a microbial infection, so the application does not expressly recite a step of treating sun exposed skin. However, the claimed invention embraces treating sun exposed skin with the same composition as claimed as follows; for example, MRSA infections mostly occur on the skin (i.e., sun exposed skin) (PennMedicine, “causes” paragraph), therefore there is an overlap in the populations of patients being treated for microbial infections and patients having sun exposed skin, even though that limitation is not expressly recited.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
Applicants comment on page 8 filed 12/15/2025 requesting that the nonstatutory double patenting rejections be held in abeyance is noted.
Regarding Applicant's argument that the double patenting rejections should be held in abeyance, the double patenting rejections apply to the claims as they are currently written, therefore these double patenting rejections are maintained. Further, Applicants' request to hold the rejection in abeyance is not a proper response to a rejection. Rather, a request to hold a matter in abeyance may only be made in response to an objection or requirements as to form (see MPEP 37 CFR 1.111(b) and 714.02). Thus, the rejection is maintained in the absence of a terminal disclaimer.
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.
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 52, 54-57, 59, 66-68, 70, and 72-73 are rejected under 35 U.S.C. 103 as being unpatentable over Weinstein et al. (US 4,753,958, Published June 28, 1988) in view of Houle et al. (US PG Pub 2006/0265028 A1, Published November 23, 2006) in further view of Wright et al. (US20030068375A1, Published 04/10/2003) in further view of Kuhn et al. (US20040151793A1, Published 08/05/2004).
Applicant’s invention
The applicant’s claims are drawn to a method for treating sun exposed skin in a subject in need thereof, comprising administering to the subject a pharmaceutical composition comprising porfimer sodium, one or more gelling agents, one or more permeation enhancers, polysorbate 80 glycerin, benzyl alcohol, phenoxyethanol, and hexylene glycol, wherein the gelling agent is hydroxypropyl cellulose, and wherein the composition is applied to the sun exposed skin; and light is applied to the sun exposed skin.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claim 52, 54 and 72, Weinstein et al. teaches a topical or intradermal preparation for the treatment of hyperproliferative epithelial diseases (i.e., pharmaceutical composition) (col 4, lines 16-17). Weinstein continues to teach a therapeutically effective amount of the component of Hematoporphyrin derivative is used (col 4, lines 50-51), and further teaches a fraction of HPD enriched in the active component, can also be purchased from Photofrin Mecidal,Inc., under the trade name Photofrin II ( col 6, lines 3-8) which is porfimer sodium (CAS Registry No 87806-31-3). Weinstein further teaches on exposing said treated area of skin to radiation that photoactivates said component of Hematoporphyrin Derivative (i.e., light) (col 4, lines 60-64). Weinstein continues to teach hexylene glycol as a carrier (col 6, line 63). Weinstein also teaches a preferred radiation source is red light (620-640nm, corresponding to an HPD absorption band). Such wave lengths are used for the treatment of tumors because of deeper tissue penetration by the longer wave length light (col 8, lines 23-27).
Regarding claims 55 and 66-67, Weinstein teaches additional example of diseases which can respond to the treatment described herein include atopic dermatitis, vitiligo, non
specific dermatitis, primary irritant contact dermatitis, allergic contact dermatitis, ichthyosis, epidermolytic hyperkeratosis, premalignant sun-induced keratosis, nonmalignant keratosis (i.e., seborrheic keratosis), actinic keratosis, and seborrheic dermatitis (col 5, lines 47-54).
Regarding claims 59, 64, and 72 Weinstein teaches that the light source, placed 10 cm above the exposure site, delivered doses of 8.8 J/cm2, 17.6J/cm2 or 35.2J/cm2, representing exposure times of 15, 30, and 60 minutes, respectively (col 10, lines 47-54).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
Weinstein does not expressly teach about one or more gelling agent in the composition wherein at least one gelling agent is hydroxypropyl cellulose, polysorbate 80, glycerin, benzyl alcohol, and phenoxyethanol. Weinstein also does not expressly teach wherein the pharmaceutical composition comprises one or more permeation enhancers selected from the group consisting of propylene glycol SR, diethylene glycol monoethyl ether, and dimethyl sulfoxide (DMSO), in an amount ranging from about 65% wt to about 75 %. Lastly, Weinstein does not expressly teach the porfimer sodium amount ranging from about 0.4 % to about 0.6% w/w in the pharmaceutical composition. These deficiencies are cured by Houle et al, Wright et al, and Kuhn et al.
Houle et al. is directed to a method of administering an effective and/or sufficient amount of a photosensitizer to the target skin, then irradiating the target skin with energy comprising
one or more wavelength capable of activating said photosensitizer for a time period sufficient to activate the photosensitizer (abstract). Houle discloses that preferably the photosensitizers herein are selected from pro-porphyrins, porphyrins, and mixtures thereof and further list porfimer sodium (available as Photofrin™) as an example (page 3, paragraph [0036]). Houle discloses that the composition may comprise any component that is suitable for the intended purpose such as conventional delivery vehicles and excipients including gelling agents (page 5, paragraph preferably between about 0.01 to about 1 % w/w and particularly preferred in the use of about a 0.2% w/w topical formulation (page 7, paragraph [0072]). Houle continues to disclose that preferred viscosity modifiers are selected from polyethylene glycols, acrylic acid-based polymers (carbopol polymers or carbomers), xanthan gum, polyvinyl alcohol, and poloxamers (page 6, paragraph [0065]). Houle also teaches suitable excipients or carriers for use with photosensitizers such as glycerol (i.e., glycerin) (page 5, paragraph [0056]). Houle further teaches the use of solvents acceptable for use in the treatment of skin tissues such as benzyl alcohol (page 6, paragraph [0063]). Houle further discloses that preferred skin-penetration enhancers for use herein include, but are not limited to, diethylene glycol, monoethyl ether, polysorbate 80 (pages 5-6, paragraph [0059]) and it is preferred that the formulations comprise from about 0.1 % to about 99%, and even more preferably from about 15% to about 75%, by weight of skin penetration enhancer (page 6, paragraph [0060]). Lastly, Houle teaches suitable preservatives include parabens, benzyl alcohol, disodium EDTA etc. (page 6, paragraph [0069]).
In the analogous art of pharmaceutical formulations, Wright teaches the pharmaceutical formulation comprises a gelling agent such as hydroxypropyl cellulose, polyethylene glycols, acrylic acid-based polymers (carbopol polymers or carbomers), xanthan gum, polyvinyl alcohol, and poloxamers (page 4, paragraph [0049]).
In the analogous art of treating damaged skin, Kuhn teaches suitable preservatives such as phenoxyethanol, benzyl alcohol, and methyl or propylparaben (page8 , paragraph [0156]).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-143)
Regarding claim 52, it would have been prima facie obvious to one of ordinary skill in the art at the time of the instant invention to administer Weinstein’s preparation as treatment to subjects with hyperproliferative epithelial diseases. The artisan of ordinary skill would have been motivated to do so in order to treat e.g., additional diseases which can respond to the treatments describes including sun exposed skin. Furthermore, this embodiment is contemplated in the broader disclosure of Weinstein, as noted above. One having ordinary skill in the art would have understood in view of Houle that the composition could contain a conventional delivery vehicles such as glycerol (i.e., glycerin), benzyl alcohol, polysorbate 80 and excipients including gelling agents (see MPEP 2144.07).
With regards to wherein the gelling agent is hydroxypropyl cellulose in instant claim 52, Weinstein is silent about the use of gelling agents. Houle teaches about the gelling agent being selected from polyethylene glycols, acrylic acid-based polymers (carbopol polymers or carbomers), xanthan gum, polyvinyl alcohol, and poloxamers (page 6, paragraph [0065]). One would have understood in view of Wright that the pharmaceutical formulation comprises a gelling agent such as hydroxypropyl cellulose, polyethylene glycols, acrylic acid-based polymers (carbopol polymers or carbomers), xanthan gum, polyvinyl alcohol, and poloxamers (page 4, paragraph [0049]). It would have been obvious to one of ordinary skill to use hydroxypropyl cellulose as a gelling agent in Weinstein’s preparation as treatment to subjects with hyperproliferative epithelial diseases because Houle teaches gelling agent being selected from polyethylene glycols, acrylic acid-based polymers (carbopol polymers or carbomers), xanthan gum, polyvinyl alcohol, and poloxamers and Wright teaches hydroxypropyl cellulose as well as polyethylene glycols, acrylic acid-based polymers (carbopol polymers or carbomers), xanthan gum, polyvinyl alcohol, and poloxamers (page 4, paragraph [0049]). It would have been prima facie obvious to exchange or combine the known gelling agents described by Houle with the known gelling agent hydroxypropyl cellulose (as taught by Wright) because these substances were known to serve the same purpose. See MPEP 2144.06.
With regards to the pharmaceutical composition comprising phenoxyethanol in instant claim 52, Houle teaches suitable preservatives include parabens, benzyl alcohol, disodium EDTA etc. (page 6, paragraph [0069]). One would have understood in view of Kuhn in the analogous of treating damaged skin, suitable preservatives such as phenoxyethanol, benzyl alcohol, and methyl or propylparaben (page 8, paragraph [0156]). It would have been obvious to one of ordinary skill in the art to have preservatives such as phenoxyethanol in Weinstein’s preparation as treatment to subjects with hyperproliferative epithelial diseases because Houle teaches suitable preservatives include parabens, benzyl alcohol, disodium EDTA etc. (page 6, paragraph [0069]) and Kuhn teaches suitable preservatives such as phenoxyethanol, benzyl alcohol, and methyl or propylparaben. Therefore phenoxyethanol was known to serve the same purpose of a preservative in a pharmaceutic composition such as Weinstein’s preparation. See MPEP 2144.06.
Regarding claims 56, 57 and 73, wherein the subject does not suffer from pain when the light is applied to the sun exposed skin, the methods of the Weinstein and Houle encompasses not experiencing pain because no limitation of time of exposure or amount of active agent and no particular limitation on the pain sensitivity of the subject is recited in the instant claims. Not necessarily every patient would experience pain in the same way.
Regarding claims 59, 64 and 72 Weinstein teaches that the light source, placed 10 cm above the exposure site with exposure times of 15, 30, and 60 minutes. It would have been obvious to one of ordinary skill in the art to apply the composition to the skin for at least as long as the exposure time. Weinstein teaches that the composition is administered in a therapeutically effective amount, so the effective time frame of exposure time to the skin would be routine experimentation and is practiced by one of ordinary skill. Where the general conditions
of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable
ranges by routine experimentation. In re Aller, 220 F. 2d 454, 105 USPQ 233 (CCPA 1955). In
addition, according to the MPEP, “It is to be presumed also that skilled workers would as a
matter of course, if they do not immediately obtain desired results, make certain experiments and
adaptations, within the skill of the competent worker.” (MPEP 716.07).
Regarding claim 68, both Weinstein and Houle teach on applying a pharmaceutical composition comprising a porfimer sodium (Photofrin) to treat an affected area with light being applied as well. It would have been obvious to one of ordinary skill, in the art at the time, to modify the teachings of Weinstein to incorporate the teachings of Houle, thus having a concentration of the photosensitizer (i.e., porfimer sodium) in the pharmaceutical composition ranging in the amount of preferably between 0.01% to about 1% w/w (page 7, paragraph [0072]). The skilled artisan would have had a reasonable expectation of success because the preferred concentration disclosed by Houle is in range of the concentration recited in the claims.
Regarding claim 70, having a pharmaceutical composition which also comprises one or more one or more permeation enhancers selected from the group consisting of propylene glycol SR, diethylene glycol monoethyl ether, and dimethyl sulfoxide (DMSO), in an amount ranging from about 65% wt to about 75% wt would be obvious when the prior art is teaching about penetration enhancers. Houle teaches that preferred skin-penetration enhancers for use herein include, but are not limited to, diethylene glycol monoethyl ether, (page 5, paragraph [0059]). Houle further discloses that it is preferred that the formulations comprise from about 0.1 % to about 99%, preferably from about 0.1 % to about 90%, more preferably from about 5% to about 90%, even more preferably from about 15% to about 75%, by weight of skin penetration enhancer (page 6, paragraph [0060]). This range overlaps with the range recited in the instant claims. See MPEP 2144.05(I): In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). One of ordinary skill in the art would have reasonable success of adding a penetration enhancer to the pharmaceutical composition for aiding the delivery of the photosensitizing agent and this would merely require routine tests of several different concentrations to optimized the known aiding effect of the penetration enhancer.
Claims 58 and 61-64 are rejected under 35 U.S.C. 103 as being unpatentable over Weinstein et al. (US 4,753,958, Published June 28, 1988) in view of Houle et al. (US PG Pub 2006/0265028 A1, Published November 23, 2006) in further view of Wright et al. (US20030068375A1, Published 04/10/2003) in further view of Kuhn et al. (US20040151793A1, Published 08/05/2004) further in view Kaw et al. (Kaw, J Am Acad Dermatol (2020) pages 862-868).
Applicant’s Invention
Weinstein and Houle render obvious all the limitations of instant claim 52. Applicant’s claim 58, adds further the limitations that wherein the subject suffers from a level pain 2, 1 or
less per the visual analog scale of pain when the light is applied to the sun exposed skin. The instant claim 61 adds further limitation that the subject does not develop edema or pruritus from treatment on the sun exposed skin. Applicant’s claims 62 and 63 add further the limitations wherein the subject does not develop erythematous lesions greater than a score of 1 and also higher than 1 or 2 per erythema scale from said treatment on the sun exposed skin.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claims 58, and 61-64, Weinstein and Houle both teach about a pharmaceutical composition for treatment of hyperproliferative epithelial diseases with a component of Hematoporphyrin derivative, exposing said treated area with radiation that photoactivates said component, and including a gelling agent in the composition that is applied to the affected area of skin of the subject.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Weinstein and Houle both teach about a pharmaceutical composition for treatment of hyperproliferative epithelial diseases (col 4, lines 16-17) with a component of Hematoporphyrin derivative (col 4, lines 50-51), exposing said treated area with radiation that photoactivates said component (col 4, lines 60-64), and including a gelling agent in the composition (page 5, paragraph [0056]), that is applied to the affected area of skin of the subject; wherein the subject does not develop erythematous lesions greater than a score of 1 and also higher than 1 or 2 per erythema scale from said treatment on the sun exposed skin, Weinstein and Houle do not expressly teach about subject suffering from a level pain 2, 1 or less per the visual analog scale of pain when the light is applied to the sun exposed skin, and that the subject does not develop edema or pruritus from treatment on the sun exposed skin . However, this deficiency is cured by Kaw et al.
Kaw et al. discloses, a simple modification of the PDT regimen that nearly eliminates pain during illumination yet provides the same clinical benefit in terms of AK lesion clearance (page 2, paragraph “capsule summary”). Kaw continues to teach that several secondary endpoints were measured. For pain assessment, patients were asked every 5 to 10 minutes during illumination to report their pain on a 0-to-10 visual analog scale (VAS)( page 3, paragraph “outcome measures”). Kaw further teaches ALA-PDT of extensive AK lesions of the face and scalp, using a new simultaneous incubation illumination regimen, causes minimal pain yet provides clinical efficacy comparable to traditional PDT regimens. This new simultaneous approach should significantly improve patient care by reducing pain, discomfort, and patient anxiety (page 6, “conclusion” paragraph). Kaw further teaches erythema, an early indicator of PDT response, was typically very mild at the conclusion of treatment (page 4, “results” paragraph 2). Kaw further teaches percentage of patients who reported the particular symptoms itching (i.e., pruritus) or swelling (i.e., edema) (supplementary table 3).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-143)
Regarding claim 58, it would have been prima facie obvious to one of ordinary skill in the art at the time of the instant invention to adjust application protocol of the pharmaceutical composition of Weinstein and Houle to the subject in order to minimize pain sensation, and one having ordinary skill in the art would have understood in view of Kaw to use the VAS pain scale to assess the level of pain experienced by the subject. Kaw teaches the use of a different photodynamic therapy agent, 5-aminolevulinic acid (ALA), reduces pain drastically (page 5, “discussion” paragraph). One of ordinary skill in the art would have been motivated optimize the treatment timing in order to minimize the unpleasant side effect of pain for the patient. The skilled artisan would have had a reasonable expectation of success because relative timing of light and photodynamic agent had been demonstrated to affect pain sensation in a very similar protocol. The examiner notes that although claims 56-57 and 73 are rejected above, these claims also would have been prima facie obvious for the reasons set fourth for claim 58.
Regarding claim 61, it would have been prima facie obvious to one of ordinary skill in the art at the time of the instant invention to apply the pharmaceutical composition of Weinstein and Houle to the subject. One having ordinary skill in the art would have understood in view of Kaw that not 100 percent of the patients reported any sign of edema or pruritus. Kaw discloses that 43 percent reported itching on day 1 and 22-26 percent reported swelling on day 1 of treatment(supplementary table 3). The skilled artisan would have reasonable expectation of success in treating subjects wherein they do not develop edema or pruritus disclosed by Kaw because as explained above, the skilled artisan would have recognized that not 100 percent of the subjects reported any side effects which read to the instant claim.
Regarding claims 62 and 63, it would be obvious to one of ordinary skill in the art to optimize the parameters of treatment duration and timing of application of the photodynamic therapy composition relative to timing of light application to reduce the undesirable side effect of pain. Kaw discloses that order of application matters in using ALA for photodynamic therapy on subjects with actinic keratosis and it would have been a matter of routine for one of ordinary skill to test different relative times of application and durations of treatment and measure consequent pain sensation. "Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05.
With regards to claims 64 and 65, these limitations were obvious exactly as set forth for claims 59 and 60 in the rejection above.
Claim 71 is rejected under 35 U.S.C. 103 as being unpatentable over Weinstein et al. (US 4,753,958, Published June 28, 1988) in view of Houle et al. (US PG Pub 2006/0265028 A1, Published November 23, 2006) in further view of Wright et al. (US20030068375A1, Published 04/10/2003) in further view of Kuhn et al. (US20040151793A1, Published 08/05/2004) further in view Huang et al. (Huang, ACS Infectious Diseases, (2017) pages 320-328).
Applicant’s invention
Weinstein and Houle render obvious all the limitations of instant claim 52. Applicant’s claim 71 adds further the limitations that the pharmaceutical composition comprises a
potentiator of PDT selected from the group consisting of sodium azide, sodium thiocyanate, sodium bromide and potassium iodide (KI), sodium iodide and potassium selenocyanate (KSeCN), in an amount ranging from 1.3 % wt to about 2 % wt.
Determination of the scope and the content of the prior art
(MPEP §2141.01)
Regarding claim 71, Weinstein teaches a topical or intradermal preparation for the treatment of hyperproliferative epithelial diseases (i.e., pharmaceutical composition) with a therapeutically effective amount of the component of Hematoporphyrin derivative with an enriched active component under the trade name Photofrin II which is porfimer sodium, and exposing said treated area of skin to radiation that photoactivates said component of Hematoporphyrin Derivative (i.e., light). Houle teaches that the composition may comprise any component that is suitable for the intended purpose such as conventional delivery vehicles and excipients including gelling agents.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Weinstein and Houle teaches about a pharmaceutical composition for treatment of hyperproliferative epithelial diseases (col 4, lines 16-17) with a component of Hematoporphyrin derivative (col 4, lines 50-51), exposing said treated area with radiation that photoactivates said component (col 4, lines 60-64), and includes a gelling agent in the composition (page 5, paragraph [0056]), Weinstein and Houle do not expressly teach on potentiator of PDT selected from consisting of sodium azide, sodium thiocyanate, sodium bromide and potassium iodide (KI), sodium iodide and potassium selenocyanate (KSeCN), in an amount ranging from 1.3 % wt to about 2 % wt. However, these deficiencies are cured by Huang et al.
Huang et al. is directed to antimicrobial photodynamic inactivation (i.e., pharmaceutical composition) where aPDI involves the use of dyes called photosensitizers (PS) in combination with visible light to produce reactive oxygen species (ROS) that kill the microbial cells (page 1, paragraph 1). Huang continues to teach published papers showing that aPDI using several different PS can be potentiated by the addition of the nontoxic inorganic salt potassium iodide (page 1, paragraph 3). Huang further teaches that as can be seen in Figure 1 all five species were eradicated by the addition of KI at concentrations up to 100 mM (page 2, paragraph 7). Note that 100mM is 16.6 g/L or about 1.7 wt% as in the instant claim.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-143)
Regarding claim 71, it would have been obvious to one of ordinary skill in the art at the time of the instant invention to combine the teachings of Weinstein, Houle, and Huang to achieve a pharmaceutical composition comprising porfimer sodium, one or more gelling agent, and light, which further comprises potassium iodide (KI) as a potentiator of PDT, in an amount ranging from 1.3% wt to about 2% wt. Weinstein and Houle are directed to a topical formulation of porfimer sodium (Photofrin), and Huang teaches addition of KI at 100mM can transform traditional anticancer PS such as Photofrin into powerful antimicrobial PS that can eradicate Gram-negative bacteria (as well as Gram-positives and fungi). One would have been motivated to add KI to the composition of Weinstein/Houle in order to increase the efficacy of the PDT agent.
Response to Arguments
Applicants arguments filed 12/15/2025 have been fully considered but they are not persuasive.
On page 6 of Applicants remarks, Applicants argue that Houle like Weinstein does not teach the specific pharmaceutical composition comprising porfimer sodium and one or more permeation enhancers, polysorbate 80, glycerin, benzyl alcohol, phenoxyethanol, hexylene glycol, wherein the gelling agent is hydroxypropyl cellulose, and that Houle teaches “preferred formulations” while completely silent regarding specific pharmaceutical excipients useful for treating sun exposed skin, therefore one would not have been able to arrive at the claimed pharmaceutical composition without impermissible hindsight knowledge. Applicants further argue that Kaw and Wright are also silent regarding claimed specific pharmaceutical composition excipients.
These arguments are not persuasive and addressed in the 103 rejection above. In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
The Examiner also points out with regards to the argument wherein Houle teaches “preferred formulations” while completely silent regarding specific pharmaceutical excipients useful for treating sun exposed skin, Disclosed examples and preferred embodiments do not constitute a teaching away from a broader disclosure or nonpreferred embodiments. In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). “A known or obvious composition does not become patentable simply because it has been described as somewhat inferior to some other product for the same use.” In re Gurley, 27 F.3d 551, 554, 31 USPQ2d 1130, 1132 (Fed. Cir. 1994) (The invention was directed to an epoxy impregnated fiber-reinforced printed circuit material. The applied prior art reference taught a printed circuit material similar to that of the claims but impregnated with polyester-imide resin instead of epoxy. The reference, however, disclosed that epoxy was known for this use, but that epoxy impregnated circuit boards have “relatively acceptable dimensional stability” and “some degree of flexibility,” but are inferior to circuit boards impregnated with polyester-imide resins. The court upheld the rejection concluding that applicant’s argument that the reference teaches away from using epoxy was insufficient to overcome the rejection since “Gurley asserted no discovery beyond what was known in the art.” Id. at 554, 31 USPQ2d at 1132.). Furthermore, “[t]he prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….” In re Fulton, 391 F.3d 1195, 1201, 73 USPQ2d 1141, 1146 (Fed. Cir. 2004).
On pages 6-7 of Applicants remarks, Applicants argue that Weinstein, Houle, Wright, Huang nor Kaw does not teach the claimed pharmaceutical composition. The applicant further argues that Kaw teaches blue light which has a wavelength between 450-495 made the patients experience less pain during simultaneous illumination. So based on Kaw, one would be motivated to use blue light for simultaneous illumination to reduce pain. Applicants further argue that the Office has not provided sufficient reasons as to why one skilled in the art would be motivated to make the proposed modification to remove Kaw’s blue light; ALA photodynamic therapeutic agent; and simultaneous illumination method to arrive at the claimed method.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The examiner points out Kaw was not relied on to address the specific wavelength (i.e., blue light). In view of Kaw, one of ordinary skill in the art would have been motivated optimize the treatment timing in order to minimize the unpleasant side effect of pain for the patient. The skilled artisan would have had a reasonable expectation of success because relative timing of light and photodynamic agent had been demonstrated to affect pain sensation in a very similar protocol. The Examiner reiterates that the Examiner is not relying on the exact methodology of Kaw in using blue light, ALA photodynamic therapeutic agent, and simultaneous illumination but only relies on the teaching of Kaw for the modification of timing and the use of the visual analog scale of pain as motivation for one of ordinary skill in the method of Weinstein to adjust the timing of light and photodynamic agent for the reduction of pain in the subjects. s
See MPEP 2143.01(I): The disclosure of desirable alternatives does not necessarily negate a suggestion for modifying the prior art to arrive at the claimed invention. In In re Fulton, 391 F.3d 1195, 73 USPQ2d 1141 (Fed. Cir. 2004), the claims of a utility patent application were directed to a shoe sole with increased traction having hexagonal projections in a "facing orientation." 391 F.3d at 1196-97, 73 USPQ2d at 1142. The Board combined a design patent having hexagonal projections in a facing orientation with a utility patent having other limitations of the independent claim. 391 F.3d at 1199, 73 USPQ2d at 1144. Applicant argued that the combination was improper because (1) the prior art did not suggest having the hexagonal projections in a facing (as opposed to a "pointing") orientation was the "most desirable" configuration for the projections, and (2) the prior art "taught away" by showing desirability of the "pointing orientation." 391 F.3d at 1200-01, 73 USPQ2d at 1145-46. The court stated that "the prior art' s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed…." Id. In affirming the Board' s obviousness rejection, the court held that the prior art as a whole suggested the desirability of the combination of shoe sole limitations claimed, thus providing a motivation to combine, which need not be supported by a finding that the prior art suggested that the combination claimed by the applicant was the preferred, or most desirable combination over the other alternatives. Id. See also In re Urbanski, 809 F.3d 1237, 1244, 117 USPQ2d 1499, 1504 (Fed. Cir. 2016).
In Ruiz v. A.B. Chance Co., 357 F.3d 1270, 69 USPQ2d 1686 (Fed. Cir. 2004), the patent claimed underpinning a slumping building foundation using a screw anchor attached to the foundation by a metal bracket. One prior art reference taught a screw anchor with a concrete bracket, and a second prior art reference disclosed a pier anchor with a metal bracket. The court found motivation to combine the references to arrive at the claimed invention in the "nature of the problem to be solved" because each reference was directed "to precisely the same problem of underpinning slumping foundations." Id. at 1276, 69 USPQ2d at 1690. The court also rejected the notion that "an express written motivation to combine must appear in prior art references…." Id. at 1276, 69 USPQ2d at 1690.
On pages 7-8 of Applicants remarks, Applicants argue that applicants data described in the application illustrates that the claimed method achieved safe and significantly lower PDT-induced pain in the treated patients during treatment. Applicant further argues that when the visual analog scale was used to collect information regarding pain with the study in Examples 6-11, no adverse side effects of pruritus, pain or edema was reported.
This argument is not persuasive. Please refer to MPEP 716.02(b) which details the burden on Applicant to establish that results in a side-by-side comparison to the closest prior art are unexpected and significant. Specifically, applicant must establish that differences in results are in fact unexpected and unobvious and are of both practical and statistical significance. Additionally, evidence of unexpected properties must be commensurate in scope with the claims. Applicants have argued that when the visual analog scale was used to collect information regarding pain associated with the study in examples 6-11, no adverse side effects of pruritus, pain or edema was reported. Applicants refer to examples 6-11 in their remarks but did not specify which experiment/table has the superior data. In the instant case, data of record is expected and/or does not appear to show statistical or practical significance. No comparison to the closest prior art appears to have been made of record as each of the examples 6-11 are compositions according to the instant invention. Thus, no improvement over prior art methods has been established at this point in prosecution. The Examiner points out that the Applicants have not provided a side-by-side comparison to the closet prior art wherein Houle teaches a formulation comprising a porfimer sodium, polysorbate 80, glycerin, benzyl alcohol, preservatives, and gelling agents which renders obvious the claims. Houle’s composition was known except for the specific gelling agent being hydroxypropyl cellulose, and the specific preservative being phenoxyethanol, but applicant has not established any particular unexpectedly improved benefit due to inclusion of those substances. Applicants also have not compared to Weinstein, however one would expect to have better delivery in a vehicle that is designed to deliver a composition to the skin. The examiner also points out that the Applicants examples only compare formulations containing an amount of porfimer sodium with or without potassium iodide, wherein the instantly claimed pharmaceutical composition comprises more than just porfimer sodium and potassium iodide. The examiner further notes that no statistical analysis has been performed, thus Applicant has not established statistical significance of the results presented in examples 8-11.
Conclusion
No claims are allowed.
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AFUA BAMFOAA BOATENG Examiner, Art Unit 1617
/ALI SOROUSH/Supervisory Patent Examiner, Art Unit 1614