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 .
Current Status
This action is responsive to the amended claims of 02/17/2026. Claims 1-20 are pending. Claims 19-20 are new. Claims 4-6, 13-14, and 17-18 are withdrawn. Claims 1-3, 7-12, 15-16, and 19-20 have been examined on the merits.
Election/Restrictions
Applicant’s amendments have not overcome the prior art rejections of record. Thus, the Markush search has not been further extended since the search for the elected species still retrieves prior art.
The elected species read on claims 1-3, 7-12, 15-16, and 19-20.
Claims 4-6, 13-14, and 17-18 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/08/2025.
Priority
The effective filing date remains 07/10/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 02/17/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Response to Arguments
Examiner acknowledges receipt of and has reviewed the amendments and remarks of 02/17/2026; no new matter is found.
The objection to claims 3, 12, and 15-16 is withdrawn since the punctuation has been amended as suggested by Examiner.
The 112b rejections of claims 1-3, 7-12, and 15-16 are withdrawn since “the composition” is now “a composition” in both independent claims 1 and 9.
The 102(a)(1) rejection of claims 1-3, 7-8, and 16 over YEN (Yen, C.F. et al. J. Am. Acad. Dermatol., June 2018, 78, e143-144) is maintained and modified below to account for the amendments to the claims. Applicant's arguments have been fully considered but they are not persuasive. Applicant argues the claims are drawn to a method of reducing and preventing EGFRI-damage to normal epithelial cells. Applicant refers to “pre-treatment” cells as “normal epithelial cells” – i.e., cells not yet damaged by EGFRI. However, the instant disclosure does not restrict/define “normal epithelial cells” to undamaged cells. The disclosure is open-ended: e.g., Pg. 3 ¶11 “In one embodiment, said normal epithelial cells are epithelial cells that have not been damaged by an EGFRI.” Further, in the relevant art, evidenced by HOGAN (Hogan, C. et al., Nature Cell Biology, 2009, 11, 460-467), normal epithelial cells are understood as non-cancerous cells or non-transformed cells (Pg. 460 Abstract). Thus, under the broadest reasonable interpretation (BRI), the claims are drawn to treatment of any epithelial cells that are “normal” – which includes those not yet damaged by EGFRI but also those that are just not cancerous (no indication as to their EGFRI-damage status is invoked).
Thus, the amendment to claim 1 does not restrict the scope of the method to only cells not yet damaged by EGFRI. Therefore, the argument is not in line with the scope of the claims.
The 102(a)(1) rejection of claims 1-3, 7-12, and 15-16 over YEN (Yen, C.F. et al. International Journal of Dermatology, Nov. 2019, 59(3), 326-332) is maintained and modified below to account for the amendments to the claims. Applicant's arguments have been fully considered but they are not persuasive. For claims 1-3, 7-8, and 16, Applicant’s arguments have been addressed above, ¶11. For claims 9-12 and 15, Applicant argues the combination of a beta-1 adrenergic receptor antagonist with an EGFRI significantly enhances the anticancer effects of the EGFRI (see instant FIG. 6-7). Further, YEN does not teach such enhancement. Applicant did not amend claim 9.
This is not persuasive since unexpected results cannot be used to overcome anticipatory rejections. In this case, claim 9 is not so narrowly drawn to a method wherein the beta-1 antagonist must enhance the EGFRI. Under the BRI, as long as both drugs are administered during a method of treating cancer, the claims are met.
The 102(a)(1) rejection of claims 1-3, 8-9, 11-12, and 15-16 over SOLLENA (Sollena, P. et al. Drugs in Context, Nov. 2019, 8, 1-7) is maintained and modified below to account for the amendments to the claims. Applicant's arguments have been fully considered but they are not persuasive. The same arguments addressed in ¶11-12 were applied here.
The 103 rejection of claims 1-3, 7-12, and 15-16 over SOLLENA (Sollena, P. et al. Drugs in Context, 2019, 8, 1-7) in view of YEN (Yen, C.F. et al. J. Am. Acad. Dermatol., June 2018, 78, e143-144) is maintained and modified below to account for the amendments to the claims. Applicant's arguments have been fully considered but they are not persuasive. As stated above, Applicant appears to intend “normal epithelial cells” to be narrowed to only those not yet damaged by EGFRI. While the unexpected results do show an improved outcome when the beta-1 antagonist is administered before EGFRI treatment to undamaged cells and the Figs. 6-7 show synergy at certain dosages, the claims are not so narrow (see ¶11-13 above). Further, the rejection is not made over whether it would be obvious to preventatively administer the composition to undamaged cells, the rejection is made over swapping one beta-1 antagonist for another in a method of treating (reducing) EGFRI damage and inhibiting cancer. The pairing of a beta-1 antagonist and EGFRI is known in the applied art.
Both the anticipatory and obviousness type non-statutory double patenting (NSDP) rejections of the claims 1-3 and 7-8 & claims 1-3, 7-12, and 15-16 over Application No. 18/021,053 are withdrawn. App. No. 18/021,053 has been abandoned.
The obviousness-type NSDP of claims 1-3, 7-12, and 15-16 over U.S. Patent No. 11,154,518 in view of SOLLENA is maintained and modified in response to the amendments. Applicant did not present any arguments.
Response to Amendment
Claim Objections
Claim 20 is objected to because of the following informalities: the use of semicolons and commas is inconsistent. Semicolons are used to separate all but the last 5 options. While the claim can be clearly interpreted wherein the semicolons separate alternative delivery modes and the commas separate modes which are utilized together due to the use of the word “and,” Applicant may want to use consistent punctuation to avoid such grouping of the final 5 modes. Further, if Applicant wants all modes to be alternatives, Examiner suggests “or” rather than “and”. Appropriate correction is required.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-3, 7-8, and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by YEN (Yen, C.F. et al. J. Am. Acad. Dermatol., June 2018, 78, e143-144; provided by Examiner 11/14/2025) evidenced by HOGAN (Hogan, C. et al., Nature Cell Biology, 2009, 11, 460-467).
YEN teaches epidermal growth factor receptor inhibitors (EGFRI) cause paronychia and lesions (Pg. e143 para 1); which are shown as lesions on the skin of a patient (Pg. e143 Fig. 1). YEN teaches the paronychia was induced by afatinib and was treated with topical betaxolol 0.25% drops (Pg. e143 para 2).
As evidenced by HOGAN, normal epithelial cells are understood as non-cancerous cells or non-transformed cells (Pg. 460 Abstract). The epithelial cells affected with paronychia/lesions in YEN fall under this definition. While they have been damaged by the EGFRI, the instant claims are not so narrow to only be drawn to treatment of un-damaged cells (see ¶11 above).
Examiner understands the topical betaxolol drops are a composition comprising an effective amount of a β-1 adrenergic receptor antagonist (instant claim 1 and 7). Further, since YEN teaches the afatinib-induced paronychia results in lesions on the skin, Examiner understands YEN as teaching a method of treating skin (instant claim 2) wherein the EGFRI-induced damage is skin barrier damage (instant claim 3). Further, since YEN teaches the EGFRI is afatinib, the method reads on instant claims 8 and 16.
Claims 1-3, 7-12, and 15-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by YEN (Yen, C.F. et al. International Journal of Dermatology, Nov. 2019, 59(3), 326-332, provided in IDS of 01/09/2023) evidenced by HOGAN (Hogan, C. et al., Nature Cell Biology, 2009, 11, 460-467).
YEN teaches non-small cell lung cancer patients were treated for paronychia and associated lesions on their fingers or toes by administration of topical betaxolol 0.25% solution once daily (Pg. 2 Methods para 1). YEN teaches paronychia is a common adverse event caused by EGFR inhibitors (Pg. 1 Abstract) and is an inflammatory process of the soft tissue around the finger- and toenails which causes lesions that are painful and bleed easily (Pg. 2 Intro para 2). YEN teaches in cancer patients treated with afatinib (i.e., the EGFR inhibitor), betaxolol treatment resulted in resolution of EGFRI-induced paronychia after about 8 weeks (Pg. 4 Results left col. para 2). YEN teaches betaxolol is an effective treatment for patients suffering from EGFR inhibitor-induced paronychia with lesions (Pg. 1 Abstract).
YEN further teaches treatment of non-small cell lung cancer by targeting the EGFR pathways is the best option, but adverse dermatological events may affect patients’ compliance with EGFR inhibitors (Pg. 2 Intro para 1). A temporary dose reduction in EGFR inhibitors is usually recommended but a dose reduction can reduce efficacy of the cancer treatment (Pg. 2 Intro para 2). During the betaxolol treatment, the EGFR inhibitor was given at the full dose (Pg. 2 Methods para 1).
As evidenced by HOGAN, normal epithelial cells are understood as non-cancerous cells or non-transformed cells (Pg. 460 Abstract). The epithelial cells affected with paronychia/lesions in YEN fall under this definition. While they have been damaged by the EGFRI, the instant claims are not so narrow to only be drawn to treatment of un-damaged cells (see ¶11-12 above).
Examiner understands the topical betaxolol solution as a composition comprising an effective amount of a β-1 adrenergic receptor antagonist (instant claim 1, 7, and 9-10). Further, since YEN teaches the paronychia results in lesions on the skin, Examiner understands YEN as teaching a method of treating skin (instant claim 2) wherein the EGFRI-induced damage is skin barrier damage (instant claim 3). Further, since YEN teaches the EGFRI is afatinib, the method reads on instant claims 8, 11-12, and 16.
Since YEN teaches a method of treating afatinib-induced skin barrier damage by administration of betaxolol in patients being treated for non-small cell lung cancer with afatinib, Examiner understands this method as anticipatory of the method of instant claims 9 and 15 (i.e., inhibiting lung cancer cells comprising administration of afatinib and betaxolol – see ¶12 above).This conclusion is further supported by the fact that the betaxolol treatment allows the EGFRI to be given at a full dose, thus retaining efficacy of the cancer treatment.
Thus, YEN teaches the method of claim 1 and its dependent claims 2-3, 7-8, and 16 and the method of claim 9 and its dependent claims 10-12 and 15.
Claims 1-3, 8-9, 11-12, and 15-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by SOLLENA (Sollena, P. et al. Drugs in Context, Nov. 2019, 8, 1-7; provided by Examiner 11/14/2025) evidenced by HOGAN (Hogan, C. et al., Nature Cell Biology, 2009, 11, 460-467).
Regarding claims 1-3, 9, and 15, SOLLENA teaches patients under treatment with afatinib for non-small cell lung cancer were diagnosed with paronychia and pyogenic granuloma-like lesions on the hands and feet; timolol 0.5% treatment was applied to the lesions twice daily (Pg. 2 Results Case series para 1 & Pg. 3 Table 1). SOLLENA teaches timolol as a beta-blocker (Pg. 1 Abstract); Examiner understands the timolol 0.5% as a composition comprising an effective amount of a β-1 adrenergic receptor antagonist (instant claim 1 and 9).
As evidenced by HOGAN, normal epithelial cells are understood as non-cancerous cells or non-transformed cells (Pg. 460 Abstract). The epithelial cells affected with lesions in SOLLENA fall under this definition. While they have been damaged by the EGFRI, the instant claims are not so narrow to only be drawn to treatment of un-damaged cells (see ¶11-13 above).
SOLLENA teaches inhibition of EGFR-driven pathways ultimately results in decreased epidermal thickness and reduced integrity of the epidermal barrier (Pg. 1 Intro para 1). SOLLENA further teaches paronychia and pyogenic granuloma-like lesions are observed in 10–15% of cancer patients treated with EGFR-I and EGFR-I-induced epidermal thinning and altered barrier function are believed to be the initiating events (Pg. 2 left col. para 1-2). Thus, SOLLENA teaches a method of treating EGFRI-induced damage to the skin barrier (instant claims 1-3).
Since SOLLENA teaches a method of treating afatinib-induced skin barrier damage by administration of timolol in patients being administered afatinib for treatment of non-small cell lung cancer, Examiner understands this method as anticipatory of the method of instant claims 9 and 15 (i.e., inhibiting lung cancer cells comprising administration of afatinib and timolol).
Regarding claims 8, 11-12, and 16, SOLLENA further teaches afatinib is an EGFR inhibitor that is a tyrosine kinase inhibitor (Pg. 1 Intro para 2).
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 1-3, 7-12, and 15-16 are rejected under 35 U.S.C. 103 as being unpatentable over SOLLENA (Sollena, P. et al. Drugs in Context, 2019, 8, 1-7; provided by Examiner 11/14/2025) evidenced by HOGAN (Hogan, C. et al., Nature Cell Biology, 2009, 11, 460-467), as applied to claims 1 and 9 above, and further in view of YEN (Yen, C.F. et al. J. Am. Acad. Dermatol., June 2018, 78, e143-144; provided by Examiner 11/14/2025).
Determining the Scope and Contents of the Prior Art:
SOLLENA, evidenced by HOGAN, teaches the method of instant claims 1-3, 8-9, 11-12, and 15-16, as laid out in the 102 rejection above. In summary, SOLLENA teaches a method of treating EGFRI-induced damage to the skin barrier (paronychia) and of inhibiting lung cancer cells comprising administration of afatinib and timolol. SOLLENA further teaches at least two patients only showed a partial response to the timolol treatment (Pg. 3 Table 1).
YEN teaches afatinib-induced paronychia was treated with topical betaxolol 0.25% drops (Pg. e143 para 2); a follow-up after 4 weeks demonstrated complete resolution of symptoms (Pg. e143 para 2). YEN teaches betaxolol is a beta-blocker (Pg. e143 para 2).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
SOLLENA, evidenced by HOGAN, does not teach wherein the beta-blocker/beta-1 adrenergic receptor antagonist is betaxolol.
YEN is silent as to whether the afatinib treatment is for treatment of lung cancer.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treatment of non-small cell lung cancer and EGFRI-induced skin barrier damage and possesses the technical knowledge necessary to make adjustments to the treatment to optimize/enhance the treatment outcomes. Said artisan has also reviewed the problems in the art regarding beta-blockers/beta-1 adrenergic receptor antagonists for treatment of paronychia and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references SOLLENA (evidenced by HOGAN) in view of YEN.
The artisan would be motivated to substitute one functional equivalence (the beta-blocker timolol) for another (the beta-blocker betaxolol) with an expectation of success, since the prior art establishes that both function in a similar manner, i.e., both SOLLENA (Pg. 3 Table 1) and YEN (Pg. e143 para 2) teach the beta-blockers are effective in treatment of afatinib-induced paronychia. Further, the artisan would have a reasonable expectation of success in replacing timolol with betaxolol since YEN teaches complete resolution of symptoms (Pg. e143 para 2).
Claims 1-3, 7-8, 16, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over YEN (Yen, C.F. et al. J. Am. Acad. Dermatol., June 2018, 78, e143-144; provided by Examiner 11/14/2025) evidenced by HOGAN (Hogan, C. et al., Nature Cell Biology, 2009, 11, 460-467) as applied to claim 1 above, further in view of FDA (FDA, GILOTRIF (afatinib) Full Prescribing Information, revised 01/2018, retrieved from www.fda.gov/drugsatfda).
Newly added claim 20 is drawn to the method of claim 1 wherein the composition is delivered orally and topically. This mode is obvious.
Determining the Scope and Contents of the Prior Art:
YEN, evidenced by HOGAN, teaches the method of instant claims 1-3, 7-8, and 16, as laid out in the 102 rejection above. Note, the betaxolol is administered topically (Pg. e143 para 2).
FDA teaches afatinib in the form of tablets for oral dosing as approved by the US FDA (Pg. 1 Left Col.) for treatment of cancer (Pg. 2 ¶1).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
YEN, evidenced by HOGAN, is silent as to the route of afatinib administration.
FDA does not teach the combination of afatinib and betaxolol.
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treatment of cancer and EGFRI-induced skin barrier damage and possesses the technical knowledge necessary to make adjustments to the mode of administration to optimize/enhance the treatment outcomes. Said artisan has also reviewed the problems in the art regarding afatinib modes of administration and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references YEN (evidenced by HOGAN) in view of FDA.
Regarding claims 1 and 20, the artisan would be motivated to deliver the afatinib orally since this is the format approved by the FDA (Pg. 1 Left Col.) for treatment of cancer (Pg. 2 ¶1). Due to approval by the FDA, the artisan would have a reasonable expectation of success. Further, since YEN teaches the betaxolol is administered topically (Pg. e143 para 2), the artisan would have a reasonable expectation of success in delivering the instant composition orally and topically.
Regarding claims 2-3, 7-8, and 16, since these limitations are anticipated, above, the claims would be similarly obvious in view of the combined references.
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 1-3, 7-12, 15-16, and 20 are rejected on the ground of obviousness-type nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 11,154,518 (reference claims) in view of SOLLENA (Sollena, P. et al. Drugs in Context, 2019, 8, 1-7; provided by Examiner 11/14/2025), as evidenced by HOGAN (Hogan, C. et al., Nature Cell Biology, 2009, 11, 460-467), and further in view of FDA (FDA, GILOTRIF (afatinib) Full Prescribing Information, revised 01/2018, retrieved from www.fda.gov/drugsatfda).
Determining the Scope and Contents of the Prior Art:
The claims of US ‘518 are drawn to a method for treating paronychia in a patient comprising administering a composition comprising an effective amount of a β-1 adrenergic receptor antagonist (ref claim 1); wherein the paronychia is induced by a targeted therapy (ref claim 2) and the β-1 adrenergic receptor antagonist is selected from the same species recited in instant claims 7 and 10 (ref claims 3 and 6). Reference claims 4-5 recite an additional therapy which are included under the broad recitation of “comprising” in the instant claims. Thus, the reference claims are drawn to a method of treating targeted therapy-induced paronychia comprising administration of β-1 adrenergic receptor antagonists. Paronychia (i.e., skin barrier damage) and the claimed β-1 adrenergic receptor antagonists are species recited in the instant claims (see instant claims 3, 7, and 10).
SOLLENA, evidenced by HOGAN, teaches the method of instant claims 1-3, 8-9, 11-12, and 15-16, as laid out in the 102 rejection, above. SOLLENA further teaches the EGFRI induced damage can significantly impair the patient’s quality of life and compliance to anticancer treatment (Pg. 1 Abstract).
FDA teaches afatinib in the form of tablets for oral dosing as approved by the US FDA (Pg. 1 Left Col.) for treatment of cancer (Pg. 2 ¶1).
Ascertaining the Differences Between the Prior Art and the Claims at Issue:
US ‘518 does not teach wherein the targeted therapy is an EGFRI (such as afatinib) nor wherein the patient is treated to inhibit cancer cells (such as lung cancer).
Resolving the Level of Ordinary Skill in the Pertinent Art:
The level of ordinary skill in the art is represented by an artisan who has sufficient background in the development of a method useful for treatment of lung cancer and EGFRI-induced epithelial/skin cell damage and possesses the technical knowledge necessary to make adjustments to the treatment to optimize/enhance the treatment outcomes. Said artisan has also reviewed the problems in the art regarding beta-blockers/beta-1 adrenergic receptor antagonists for treatment of paronychia and understands the solutions that are widely-known in the art.
Considering Objective Evidence Present in the Application Indicating Obviousness or Nonobviousness:
The instant claims are prima facie obvious in light of the combination of references US ‘518 in view of SOLLENA (evidenced by HOGAN) and in view of FDA.
The artisan would be motivated to treat EGFRI-induced paronychia by the method of US ‘518 in a patient being administered afatinib for treatment of non-small cell lung cancer in order to improve the patient’s quality of life and compliance to anticancer treatment, as suggested by SOLLENA (Pg. 1 Abstract). The artisan would have an expectation of success since both US ‘518 (ref claims 1, 3, and 6) and SOLLENA (Pg. 2 Results Case series para 1 & Pg. 3 Table 1) treat paronychia by administration of a beta-blocker/beta-1 adrenergic receptor antagonist.
The artisan would be further motivated with an expectation of success since the claims of US ‘518 are directed towards treatment of paronychia that was induced by a targeted therapy. The artisan would understand the afatinib treatment of non-small cell lung cancer taught by SOLLENA (Pg. 2 Results Case series para 1 & Pg. 3 Table 1) as a targeted treatment that induced paronychia.
Furthermore, the artisan would understand the combined treatment of afatinib and a beta-1 adrenergic receptor antagonist (recited in reference claims 3 and 6) as a method of inhibiting cancer cells in a subject, since SOLLENA teaches the combination treatment in the context of treatment for patients with non-small cell lung cancer (Pg. 2 Results Case series para 1 & Pg. 3 Table 1). Moreover, since SOLLENA suggests the patient’s quality of life and compliance to anticancer treatment (i.e., afatinib) may be improved by resolution of the paronychia (Pg. 1 Abstract), the artisan would have a motivation to administer the combination treatment (i.e., afatinib + beta-blocker) to a cancer patient in order to inhibit the cancer cells and treat any paronychia.
In view of FDA, the artisan would have a reasonable expectation of success in administering the afatinib as an oral composition. Since SOLLENA teaches the beta-blocker is topical (Pg. 2 Results Case series para 1), the artisan would find the delivery modes of instant claim 20 obvious.
Therefore, the instant claims are obvious in view of the combined references.
Conclusion
Claims 1-3, 7-12, 15-16, and 20 are rejected.
Claim 19 is objected to for its dependence on a rejected claim.
Note: the Markush search has not been fully extended. None of the art retrieved for the elected species teaches or suggests prevention of EGFRI induced damage by administering the instant composition of afatinib & betaxolol to epithelial cells not yet damaged by the EGFRI (i.e., instant claim 19). In view of the unexpected results provided in Applicants affidavit, Examiner cannot make a true assertion that this method of claim 19 would be obvious. However, upon future extension of the search, art could be retrieved for other species which anticipates claim 19. In that case, the unexpected results cannot stop an anticipatory 102-type rejection being made.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARA ELIZABETH BELL whose telephone number is (703)756-5372. The examiner can normally be reached Monday-Friday 9:00-5:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Andrew Kosar can be reached at 571-272-0913. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/S.E.B./Examiner, Art Unit 1625
/JOHN S KENYON/Primary Patent Examiner, Art Unit 1625
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