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 .
Summary
Receipt of Applicants Remarks, Arguments and Amendments filed on 06/03/2026 is acknowledged. Claims 1-28 are pending. Claim 11 is amended. Claim 12 is cancelled. Claims 1-10 and 19-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention,
Claims 11, and 13-18 are pending and under examination in this application.
Modified Rejections
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 11 and 13-18 are rejected under 35 U.S.C. 103 as being unpatentable over Seykora (WO 2012/099968 A1) in view of Epidermal growth factor receptor activation and inhibition in 3D in vitro models of normal skin and human cutaneous squamous cell carcinoma (hereinafter the reference is referred as Commandeur), Blackman (US Patent 4,883,660) and further in view of Cutaneous Adverse Effects With HER1/EGFR-Targeted Agents: Is There a Silver Lining? (hereinafter the reference is referred as Perez-Soler).
Seykora teaches compositions and methods for treating skin cancer-associated diseases by topically administering tyrosine kinase inhibitors (abstract).
Regarding claims 11, 16, 17 and 18, Seykora explicitly teaches topical compositions comprising EGFR inhibitors including erlotinib or derivatives thereof, analogs thereof, and combinations thereof (¶ 0033) in pharmaceutically acceptable carriers (¶ 0045 and ¶ 0094) for treating cutaneous Squamous Cell Carcinoma (sSCC), with the express purpose of concentrating drug at the tumor site while reducing systemic adverse effects (¶ 0028-¶ 0034). An example of pharmaceutically acceptable carriers is ethanol or DMSO and in certain embodiments, and the pharmaceutical composition is a gel or ointment having the topical formulation comprising tyrosine kinase inhibitor (s) and related compounds in amount of 0.5-1.5%, DMSO 7-9%, propylene glycol 17-19%, hydroxy propyl methyl cellulose 1-2% and water 70-73% (Table 1 of ¶ 0046 and ¶ 0094). Examples of tyrosine kinase inhibitors and related compounds suitable for use in methods of embodiments are dasatinib, erlotinib, and gefitinib, derivatives thereof, analogs thereof, and combinations thereof (¶ 0033). It is noted that Specification (¶ 0002) expressly names Epidermal Growth Factor Receptor (EGFR) inhibitor drugs erlotinib, gefitinib target the EGFR (a known oncogene) and are used for the systemic treatment of some forms of cancer and that erlotinib and gefitinib as suitable tyrosine kinase inhibitors for the claimed topical compositions. The specification describes EGFR inhibitors as a class of kinase inhibitors encompassed by the invention (¶ 0017). Regarding limitation of erlotinib or a pharmaceutically acceptable salt thereof in a concentration of about 0.5%-7.5% w/w, Seykora discloses tyrosine kinase inhibitors at 0.5-1.5 % (table 1) and notes that topical 5-FU, the standard-of-care comparator, is used at "0.5%, 2.5%, or 5.0% formulations" against the same skin lesion types (¶ 0005). Concentrations up to 7.5% w/w represent a routine upward optimization of a known range. Moreover, Seykora discloses one millimolar PP2 in DMSO (25 µL) was topically applied (¶ 0020-¶ 0022) and in Example 4, topical dasatinib, a tyrosine kinase inhibitor in topical of 1% ointment formulation in DMSO 8% (page 25, line 6-7, and Table 2) and further discloses that the compositions deliver erlotinib topically, specifically to avoid systemic adverse effects and distinguishes topical from oral/systemic administration to reduce systemic toxicity and that topical localization avoids systemic EGFR inhibition, which is the source of the acneiform rash and other cutaneous toxicities well-documented for systemic erlotinib. This functional characteristic directly follows from the topical formulation (¶ 0002-¶ 0013, and ¶ 0057-¶ 0062) corresponding to the limitations of reduced cutaneous side-effects vs. systemic administration and reduced cutaneous toxicity. Thus, the limitation of “erlotinib or pharmaceutically acceptable salt thereof is dissolved within the composition” is expressly taught.
Regarding claim 13, the claim recites wherein the topical composition has a systemic absorption of less than 1% or less than 0.5% by weight of erlotinib or pharmaceutically acceptable salt thereof. At the concentrations described in Seykora (erlotinib at 1%–10% w/w in a topical carrier) i.e., “The data show that these small molecule kinase inhibitors can be more potent than existing agents which are used as 0.5% to 5% formulations” (page 24, lines 5-6), the low systemic absorption is a natural consequence of topical application, particularly with a near-anhydrous or penetration-limited vehicle. A PHOSITA would understand that systemic absorption from topical erlotinib compositions would be a small fraction of the 150 mg/day oral dose that produces peak plasma concentrations of approximately 1,600–3,000 ng/mL (typical Cmax). The claimed % absorption thresholds of less than 1 % follow necessarily from the disclosed topical compositions and represent nothing more than a predictable property of the disclosed formulations with a carrier applied to a localized skin area. Systemic absorption from a well-designed topical formulation is routinely below 1% by weight of the applied dose. This is not an inventive achievement but a standard feature of topical dosage forms, well within the skill of a PHOSITA formulating a topical kinase inhibitor composition.
Regarding claim 14, Seykora teaches preparations for topical administration include aqueous or non-aqueous solutions, suspensions, emulsions, and gel and examples of non-aqueous solvents are propylene glycol, polyethylene glycol, vegetable oils such as olive oil, and injectable organic esters such as ethyl oleate (¶ 0049, lines 12-15), and the experimental DMSO-based solutions (Figs. 7-13 contain no added water, and Tyrosine kinase inhibitor(s) and related compounds in DMSO (table 1) and topical 1 % dasatinib ointment in DMSO (table 1 and 2) and PP2 in DMSO (¶ 0020-¶ 0023). It is noted that Dimethyl sulfoxide (DMSO) is of low water content and commonly used in gel and ointment topical pharmaceutical formulations. However, Seykora does disclose high water content (70-73%) in the dasatinib formulation of (table 1-2) which is directly opposite of claimed limitation of water content of (0%-4%), but Seykora expressly discloses the alternative non-aqueous (anhydrous) solutions in preparation are also suggested and taught. A PHOSITA would have been motivated to use an anhydrous or near-anhydrous vehicle for erlotinib given the known sensitivity of erlotinib to acidic pH and oxidation in aqueous systems and minimizing water content to 0%- 4% w/w to preserve drug stability is a routine and expected formulation optimization.
Regarding claim 15, Seykora teaches the carrier system may also comprise, when desired, a suitable gelling agent including, but not limited to, cellulose esters such as hydroxypropyl cellulose, hydroxyethyl cellulose, polyvinylpyrrolidone, carboxy vinyl polymer and the like that may be provided in any amount necessary to thicken the composition to a desired gel consistency, and when formulated as a gel, the base composition exhibits favorable spreadability characteristics, and in addition, it remains visible on the skin surface longer, thereby instilling in the user the impression that the vehicle is more completely delivering its active ingredient(s) (¶ 0055). Therefore, the limitation of “gelling agent in an amount of about 0.1 % w/w to about 6 % w/w” is suggested and expressly taught.
Commandeur teaches transmembrane tyrosine kinase epidermal growth factor receptor (EGFR) is considered a key player in the development of cutaneous squamous cell carcinoma (SCC), and inhibition of EGFR with the small molecule tyrosine kinase inhibitor erlotinib is currently under clinical investigation in cutaneous SCC patients. the effects of EGFR activation and inhibition on normal and malignant in vitro human skin equivalents (HSEs). In healthy HSEs, increasing EGF concentrations ranging from 5 to 50 ng/mL resulted in a dramatic decrease in epidermal proliferation as immunohistochemically assessed by Ki67 and increased epidermal stress as assessed by K17 after 2 weeks of air-exposed culture. Also, higher concentrations of
EGF induced remarkable epidermal disorganization with loss of proper stratification. Similar effects were observed in HSEs generated with cutaneous SCC cell lines SCC-12B2 and SCC-13. Treatment of both healthy and SCC-HSEs with 10 µM erlotinib resulted in efficient reduction of epidermal thickness from 10 to 3 viable cell layers and counteracted EGF-induced epidermal stress. Remarkably, erlotinib treatment caused severe desquamation in healthy HSEs, reminiscent of xerosis as a known side-effect in
patients treated with erlotinib. The presented three-dimensional organotypic SCC models appear suitable for further investigations on the morphological and functional impacts of modifying EGFR signaling in cutaneous SCC, without burdening patients or
mice. The effective inhibition of epidermal growth by erlotinib in our HSEs confirms the therapeutic potential of this tyrosine kinase inhibitor for cutaneous SCC patients (abstract).
Regarding claims 11 and 13, as noted above, Commandeur teaches (1) the limitations of Erlotinib dissolved and applied to cutaneous SCC models ("treatment of both healthy and SCC-HSEs with 10 μM erlotinib resulted in efficient reduction of epidermal thickness from 10 to 3 viable cell layers", wherein erlotinib is dissolved in the treatment medium and directly applied to the skin equivalent surface, constituting topical administration of dissolved erlotinib to a cutaneous SCC model, (2) Erlotinib as therapeutic agent for cutaneous SCC, "Inhibition of EGFR with the small molecule tyrosine kinase inhibitor erlotinib is currently under clinical investigation in cutaneous SCC patients." This confirms that erlotinib was a recognized therapeutic agent being investigated specifically for cutaneous SCC, motivating topical formulation development, (3) skin toxicity of erlotinib and motivation to reduce cutaneous side effects (that erlotinib treatment caused "severe desquamation in healthy HSEs, reminiscent of xerosis as a known side-effect in patients treated with erlotinib," directly documenting the cutaneous toxicity that claims 11-13 seek to avoid by topical (as opposed to systemic) delivery.
Blackman teaches pharmaceutical compositions suitable for topical, transmucosal and oral administration may be prepared utilizing the novel gel bases. Methods of administration of topically, systemically and orally active pharmaceutical agents utilizing the novel gel bases (abstract).
Regarding claim 11 (amended), Applicant amended claim 11 to require the limitation “wherein the composition comprises more than 40% w/w glycol”. This limitation is explicitly met by Blackman. Blackman teaches anhydrous gel bases comprising a glycol solvent (such as propylene glycol or PEG 400) and an ethoxylated fatty alcohol surfactant (Column 4, lines 20-22). In Examples 1-18, Blackman discloses specific formulations where the glycol solvent comprises 90% to 99.5% w/w of the total composition. This inherently encompasses and renders obvious a formulation comprising 'more than 40% w/w glycol'."
Regarding claims 14 and 15, Blackman expressly teaches anhydrous composition "a pharmaceutical composition comprising a gel base ... the base being anhydrous." (claim 1), and Examples 1–18 disclose compositions consisting exclusively of glycol solvent (propylene glycol or PEG 400) and ethoxylated fatty alcohol surfactant, thus no water is present (0% w/w water), which falls squarely within the claimed 0%–4% w/w range. Moreover, Blackman expressly teaches gel base is formed by adding ethoxylated fatty alcohol surfactants (gelling agents) at concentrations of 0.5–10% w/w to glycol solvents (column 4, lines 20-22), and claim 1 recites gel bases comprising from about 0.5% to about 10% by weight ethoxylated behenyl alcohol (or C16-C21 ethoxylated alcohol at 2.5%–10%) in a glycol solvent, and in Examples 1–18 demonstrate specific anhydrous gel compositions with gelling agent concentrations of 0.5%, 1%, 2.5%, 5%, and 10% w/w, thus the ranges are all within or overlapping the claimed 0.1%–6% range of instant claim 15. Moreover, Blackman expressly teaches
vehicles as suitable for topical application to the skin and mucosa, and which provide rapid penetration of any compatible pharmaceutical agent, dissolved or suspended therein (column 2, lines 55-58) and a pharmaceutical composition with an active "pharmaceutical agent dissolved therein or admixed therewith." (claim 1) and in (Example 19, Table 1) demonstrate dissolution of active agents (corticosteroids, propranolol HCl, ibuprofen) in the anhydrous glycol gel base. Additionally, Blackman discloses anhydrous vehicle for moisture-sensitive active ingredients and expressly teaches that anhydrous gel bases are preferred for "active ingredients which are water-decomposable or water-insoluble" (column 1, line 6 to column 2, line 38) and that such bases "do not adversely affect moisture-degradable or water-insoluble ingredients" (column 2, line 42 to column 3, line 2). A PHOSITA would directly be motivated to selecting an anhydrous vehicle for erlotinib because erlotinib is known to be sensitive to oxidation and acidic pH in aqueous environments. Lastly, Blackman teaches superior skin penetration and topical efficacy and demonstrates in a vasoconstriction assay (Example 21) that the anhydrous glycol gel formulations were superior to commercial KENALOG® cream and ointment in delivering a topical corticosteroid, thus, providing direct motivation to use anhydrous gel vehicles to improve topical drug delivery efficacy.
Perez-Soler teaches The human epidermal growth factor receptor (HER1/EGFR) is dysregulated in many solid tumors, making it an attractive target for anticancer therapy. A number of agents that target this receptor are in use or in development. A specific adverse effect common to this class of agent is a papulopustular rash, usually on the face and upper torso, which generally occurs in a dose-dependent manner. Little is known about the etiology of this rash, and there are no clear evidence-based management recommendations. Histologic data indicate that rash may be caused by HER1/EGFR inhibition in skin, although this has not been confirmed. Findings suggest that there is a relationship between the development of rash and response and/or survival, making rash a potential surrogate marker of activity. Data from multiple studies
with cetuximab and erlotinib show a consistent relationship between rash and response, as well as between rash and survival. The relationship between rash and clinical outcome is currently less consistent for gefitinib. Some studies report a correlation, whereas others do not. The cause of the possible relationship between rash and clinical benefit remains unclear at this time, and additional studies are needed to determine the clinical utility of this observation (abstract).
Regarding claims 11 and 13, as noted above, Perez-Soler teaches that systemic erlotinib causes characteristic cutaneous toxicities by inhibiting EGFR in normal skin keratinocytes, and thus provides direct motivation for topical formulation. Perez-Soler discloses that acneiform/papulopustular rash occurs in 43–75% of patients receiving systemic EGFR inhibitors, including erlotinib (Tarceva), by inhibiting EGFR signaling in the sebaceous gland epithelium and hair follicle. The mechanism is on-target inhibition of EGFR in normal skin, the same pathway exploited therapeutically in cutaneous SCC (page 5238-5240).
It would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA) before the effective filing date of the claimed invention to arrive at the topical composition comprising erlotinib or a pharmaceutically acceptable salt thereof comprising a concentration of about 0.5 % - 7.5% as taught by Seykora. The teachings of Seykora highlight Erlotinib -Tyrosine Kinase Inhibitor (TKI), incorporated (dissolved/dispersed) in the ointment/gel base and DMSO functions as the solubilizing component for the hydrophobic small-molecule TKIs, thus Erlotinib is established as soluble in DMSO and suitable for the same carrier system in Seykora (¶ 0033). The concentration up to 7.5 % w/w represent a routine optimization of a known range, as discussed in the rejections above. The teachings in Commandeur, Blackman and Perez-Soler establishes the motivation to combine. Commandeur teaches that erlotinib was in active clinical investigation, specifically for cutaneous SCC (page 2120), confirming that erlotinib is the clinically relevant EGFR inhibitor target for the same disease treated by Seykora. Perez-Soler teaches that systemic EGFR inhibitor therapy causes dose-limiting cutaneous toxicity in 43 – 75 % of patients, establishing a clear clinical problem that topical delivery is beneficial and directly addresses. Therefore, combining these known teachings, and substituting erlotinib into the expressly disclosed topical TKI composition of Seykora, motivated by Commandeur clinical context and Perez-Soler’s toxicity profile, is reasonable to a PHOSITA to involve only known elements combined with known methods and components in a topical composition to yield predictable results. Both Seykora and Blackman establish that erlotinib is soluble in the glycol-based and DMSO-based carriers that form the basis of the claimed anhydrous vehicle (propylene glycol, PEG 400, and DMSO), providing a well-founded expectation that erlotinib will dissolve in the claimed composition at the recited concentrations. A PHOSITA would have a well-founded expectation that erlotinib could be dissolved in anhydrous propylene glycol/PEG 400 gel base at the claimed concentrations (0.5-7.5% w/w), particularly since Blackman teaches that active agents soluble in glycols are excellent candidates for its gel bases. Furthermore, Blackman provides a complete, reproducible formulation framework with 21 detailed working examples of anhydrous gel formulations and a validated in vivo performance study (example 21), thus it would have been obvious to a PHOSITA to apply this technology to erlotinib with a reasonable expectation of success. While Seykora expressly states the purpose of gelling agents, to thicken topical composition to a “desired gel consistency” (¶ 0055), a PHOSITA formulating an anhydrous topical erlotinib composition would need to achieve adequate viscosity for skin application, and too thin a composition would not adhere to the lesion site, and adding a gelling agent at 0.1-6 % w/w is the standard pharmaceutical approach to achieving this. Therefore, Seykora (¶ 0055, Table 1) in view of Blackman (Claim 1, Examples 1-18) teach gelling agent concentrations squarely within or encompassing the claimed range. The gelling agents in Seykora (HPMC, hydroxypropyl cellulose, polyvinylpyrrolidone) and Blackman (ethoxylated behenyl/cetyl/stearyl alcohols) are both established, commercially available pharmaceutical excipients with well characterized behavior in topical formulations, and their use of 0.1-1.6 % w/w to achieve gel consistency is propylene glycol or DMSO/PG carrier is fully predictable to a PHOSITA. Moreover, Blackman
demonstrates successful gel formation at concentrations as low as 0.5% w/w (Examples 1–2), confirming that gelling is achievable throughout the claimed range. Thus, predictable chemistry in this combination and it is routine topical formulation practice.
Response to Arguments
Applicant’s arguments filed June 3, 2026, have been fully considered but are found unpersuasive because of the following reasons below.
The entry of the amendment to Claim 11 introducing the structural limitation "wherein the composition comprises more than 40% w/w glycol" necessitates a modification of the 35 U.S.C. 103 rejection to explicitly address this newly added element.
Applicant's Argument 1: The ">40% w/w Glycol" Limitation and Propriety of the Combination with Blackman.
Applicant argues that Blackman is an unrelated, general-purpose gel base patent from 1988 that fails to mention erlotinib, EGFR inhibitors, or cancer, and that its combination reflects impermissible hindsight. Applicant further argues that Seykora’s formulated examples contain 70%–73% water and less than 19% glycol, meaning a generic mention of non-aqueous solvents cannot teach the specific high-glycol concentration of amended claim 11.
This argument is unpersuasive because Blackman is considered analogous art. The criteria for analogous art under 35 U.S.C. 103 are satisfied if the reference is from the same field of endeavor or is reasonably pertinent to the particular problem with which the inventor is involved. Here, both the current application and Blackman operate within the identical field of endeavor: topical pharmaceutical formulation vehicles. A Person Having Ordinary Skill in the Art (PHOSITA) tasked with formulating a topical delivery system for a specific therapeutic agent is not restricted to reviewing vehicles previously tested with that identical active ingredient; they standardly consult the general formulation art.
Explicit Motivation to Combine: Blackman explicitly addresses a well-known formulation problem, teaching that its high-glycol, anhydrous gel bases are highly preferred for "active ingredients which are water-decomposable or water-insoluble" because they prevent moisture-induced chemical degradation. Erlotinib is widely known in the art to be poorly soluble in water and susceptible to oxidation and pH-dependent degradation in aqueous environments (Column 1, line 6 to column 2, line 38).
Predictable Structural Overlap: Seykora already establishes that erlotinib is an appropriate therapeutic agent for topical skin cancer treatment and explicitly notes its compatibility with organic co-solvents like propylene glycol. Faced with the high water content (70%–73%) of Seykora's baseline formulations and the known aqueous instability of erlotinib, a PHOSITA would be directly motivated to substitute Seykora’s aqueous carrier with Blackman’s specialized anhydrous vehicle to maximize drug stability. Blackman discloses that its glycol solvent (e.g., propylene glycol or PEG 400) comprises 90% to 99.5% w/w of the total composition. This structural range clearly encompasses and renders obvious the applicant’s newly added limitation of "more than 40% w/w glycol".
Applicant's Argument 2: The "Dissolved" vs. "Dispersed" Erlotinib Limitation
Applicant contends that following the general composition guidelines of Seykora would result in a dispersed suspension rather than a composition where the erlotinib is fully "dissolved within the composition" as required by Claim 11.
This argument is unpersuasive. Claim 11 is a composition claim defined by its structural components, not a method of manufacturing. Blackman explicitly teaches that its anhydrous glycol gel bases provide a vehicle designed to achieve complete dissolution, resulting in a composition with an active "pharmaceutical agent dissolved therein" (Blackman, Claim 1 and Example 19). Furthermore, Seykora establishes that erlotinib is highly soluble in common organic carriers such as DMSO and glycols. Merging the active ingredient of Seykora into the anhydrous vehicle of Blackman predictably and inevitably results in a vehicle where the erlotinib is fully dissolved.
Applicant's Argument 3: Alleged "Teaching Away" and Unexpected Results
Applicant argues that the prior art teaches away from the claimed invention. Specifically, Applicant points out that Commandeur documents severe local skin toxicity (desquamation/xerosis) when erlotinib is applied directly to skin equivalents, and Perez-Soler attributes systemic erlotinib rash to EGFR inhibition in normal skin keratinocytes. Applicant argues that a PHOSITA would expect topical application to increase local cutaneous toxicity, making the applicant's finding of reduced cutaneous side effects at a 5 wt% concentration an unexpected, surprising result.
This argument is unpersuasive. No Teaching Away: For a prior art reference to "teach away," it must explicitly discourage a PHOSITA from following the path chosen by the applicant or state that such a path is unsuited for its intended purpose. Neither Commandeur nor Perez-Soler discourages topical formulation. On the contrary, Commandeur explicitly concludes that its findings "confirm the therapeutic potential of this tyrosine kinase inhibitor [erlotinib] for cutaneous SCC patients".
Predictable Problem vs. Solution: Perez-Soler details that systemic (oral) administration of erlotinib results in severe, widespread papulopustular rashes across the face and upper torso in up to 75% of patients. Seykora addresses this exact clinical downside by teaching that localized topical administration delivers the drug directly to the lesion site "specifically to avoid systemic adverse effects" and reduce overall systemic toxicity. Shifting from systemic exposure to a highly localized topical application inherently minimizes systemic side effects.
Standard Excipient Performance: To the extent that local irritation (such as xerosis) occurs at the application site due to EGFR inhibition, Blackman's vehicle consists almost entirely of glycols (propylene glycol/PEG). Glycols are universally recognized in the pharmaceutical arts as humectants and emollients that soften skin and mitigate localized dryness. The minimization of localized side effects is the entirely predictable functional result of using a standard, skin-protective glycol vehicle as taught by Blackman, rather than an unexpected structural synergy. Moreover, even if local xerosis occurs, it is a known and predictable side effect already documented in Commandeur, and the claim does not require complete absence of local side effects (only reduced systemic cutaneous toxicity.
Applicant's Argument 4: Functional Pharmacokinetic Thresholds
Applicant argues that the specific systemic absorption thresholds in amend claim 11 (<100 ng/mL of erlotinib or <10 ng/mL of metabolite) are not inherent properties of any topical erlotinib composition, but rather depend strictly on the distinct composition parameters demonstrated in the applicant's specification.
This argument is unpersuasive. The systemic absorption limitations recited in amended claim 11, specifically (<100 ng/mL of erlotinib or <10 ng/mL of metabolite) constitute statements of an intended functional result or pharmacokinetic property rather than a distinct structural configuration. It is well-established patent law that where the structure of the claimed composition is identical or rendered obvious by the prior art, the language of a functional property does not patentably distinguish the claim over that prior art. Because the combination of Seykora and Blackman discloses an identical structural composition—an equivalent active TKI agent (erlotinib) within an overlapping concentration range (0.5%–7.5% w/w) dissolved within an identical vehicle class (an anhydrous, high-glycol gel base)—the prior art composition will inherently exhibit the same functional performance and systemic absorption profiles when applied to localized skin lesions under identical biological conditions. Applicant has provided no comparative evidence demonstrating that a structurally identical formulation derived from the teachings of Seykora and Blackman would fail to meet these functional thresholds.
Amended Claim 11 relies on a combination of known structural elements (erlotinib and a high-glycol anhydrous base) utilized for their established properties to achieve completely predictable clinical results. The amendments fail to overcome the prior art teachings.
Conclusion
No claims are allowed.
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDRE MACH whose telephone number is (571)272-2755. The examiner can normally be reached 0800 - 1700 M-F.
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/ANDRE MACH/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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