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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 04/20/2026 has been entered.
Status of the Claims
Pursuant to the amendment dated 04/20/2026, claim 16 has been cancelled. Claims 1-13, 17-20, 24, and 27-47 had been cancelled in a previous communication.
Claims 14, 15, 21-23, 25, 26 and 48 are pending and under current examination.
All rejections not reiterated have been withdrawn.
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.
Claims 14, 15, 21-23, 25, 26, and 48 are rejected under 35 U.S.C. 103 as being unpatentable over Fink (US 2009/0018151; publication date: 01/15/2009), in view of Bobrowski (US20040067270; publication date: 04/08/2004), and Anand et al (J Pain Research 2019:12 2039-2052; publication date: 07/03/2019; cited in the IDS filed 03/03/2023), and Vinik et al. (BMC Neurology vol 16:261; publication year: 2016; cited in the IDS filed 03/03/2023).
With regard to claim 14, inter alia Fink discloses a method of preventing diabetic neuropathy by topically applying a vasodilator (abstract). The treatment is effective against diabetic complications such as neuropathy or diabetic ulcers (abstract). Fink discloses that diabetic peripheral neuropathy can present as numbness, tingling, paresthesia or pain (i.e. nonpainful presentation is included; 0010 and 0011). In diabetic patients neuropathy occurs due to a variety of causes including disruption of blood supply (0012). Diabetic neuropathy is known to be reversible (0013) and ulcers may appear on numb areas of the foot because pressure or injury goes unnoticed (0013). A major concern in diabetes is the worsening of the health of the skin, especially in the foot, and subsequent development of diabetic foot ulcers. Foot ulcers are multifactorial in origin with neuropathy, autonomic dysfunction, and vascular insufficiency all possibly contributing to this debilitating complication. (0017) In general, an agent that promotes increased microcirculation will be beneficial in relieving symptoms of diabetic neuropathy and if applied early enough in the disease process, an agent that promotes increased microcirculation could prevent the development of the complications of diabetes (0031). Fink’s invention includes a method of preventing peripheral neural and vascular ailments associated with diabetes by applying an agent that causes vasodilation to the affected area (0042).
Bobrowski discloses that capsaicin leads to a multitude of responses including vasodilation (mediated by the release of neurotransmitters from these activated nerves that cause blood vessels to relax; 0044).
Anand discloses that topical capsaicin treatment in the form of an 8% capsaicin patch may lead to nerve regeneration and restoration of sensory nerve fibers in a clinical study of neuropathic pain (abstract, pages 2046, 2047, and 2049).
In a related study evaluating treatment of painful diabetic neuropathy with 8% capsaicin patch, Vinik reported that approximately a third of patients showed improvement in various sensory functions when treated with capsaicin plus standard of care, which was a greater fraction than those treated with standard of care. Thus, one of ordinary skill in the art would have understood that topical application of capsaicin can restore some sensory function in patients with diabetic peripheral neuropathy.
It would have been prima facie obvious to apply the 8% capsaicin patch disclosed by Anand to the foot of a patient having diabetic neuropathy prior to development of an ulcer in order to prevent ulcers from forming because capsaicin was known to be a vasodilator and therefore one of ordinary skill would have recognized this substance as suitable to use in Fink’s method. Moreover, the artisan of ordinary skill would have been motivated to do so and had reasonable expectation of success because capsaicin 8% patch had been shown to restore healthy nerve physiology in another group of neuropathic pain patients (cancer induced peripheral neuropathy). The skilled artisan would have had further expectation of success in view of Vinik’s showing that capsaicin can restore some degree of sensory function in diabetic patients having painful peripheral neuropathy. Topical capsaicin had been shown to be beneficial for nerve health in cancer neuropathy and painful diabetic neuropathy. It would have been obvious and logical extension to test topical capsaicin in nonpainful diabetic neuropathy, particularly as two separate studies showed improved nerve health after treatment. The examiner notes that conclusive proof of efficacy is not required to show a reasonable expectation of success, and obviousness does not require absolute predictability, but at least some degree of predictability is required. See MPEP 2143.02(I) and (II). In this case, the fact that nerves/sensation improved in two separate studies provides the artisan of ordinary skill a reasonable expectation of success.
With respect to the limitation of claim 14 that the patient be suffering from non-painful diabetic neuropathy, it would have been obvious to apply the capsaicin as early as possible, to include when neuropathy has been identified prior to it becoming painful. One would have been motivated to do so in order to prevent the development of a foot ulcer because poor sensation (numbness) in the foot was a known contributor to ulcer development as of the instant effective filing date, particularly in view of Fink’s suggestion to treat as early as possible in the disease process (0031). Moreover
With respect to the amount of capsaicin applied per cm2 of skin required by claims 14 and 48, Anand discloses the same patch as employed in the instant invention therefore the examiner considers this to be an inherent feature of the patch. Additionally, it would have been obvious to optimize the amount of capsaicin applied in order to achieve the recognized effect of healing neuropathy. See MPEP 2144.05.
With regard to the intended outcome recited in instant claim 14, as explained above, the patch used by Anand is the same as the patch used in the instant application and therefore this outcome is deemed inherent in the method rendered obvious by Fink/Bobrowski/Anand/Vinik. Moreover, Fink indicates that improving the diabetic neuropathy will lead to some restoration of protective sensation (i.e. the patient can notice pressure on the foot because the foot is no longer numb). See above. Finally, Anand indicates that NGF levels return to levels similar to those seen in healthy skin after treatment with the capsaicin 8% patch (0247). Moreover, it is reasonable to conclude that the same patient is being administered the same active agent by the same mode of administration in the same amount in both the instant claims and the prior art reference. The fact that Applicant may have discovered yet another beneficial effect or mechanistic underpinnings of the method set forth in the prior art does not mean that they are entitled to receive a patent on that method.
With regard to claim 15, it would have been a matter of routine for one of ordinary skill to assess the optimal dosing regimen to achieve the known effect of healing neuropathy. See MPEP 2144.05.
With regard to claim 21, the patch is cutaneous.
With regard to claim 22, the patch is an 8% capsaicin patch.
With regard to claim 23, Anand discloses applying the patch for 30 min (abstract) this would give one of ordinary skill a starting point to optimize exposure time in the diabetic neuropathy patient. See MPEP 2144.05(II).
With regard to claim 25, it would have been obvious to treat a patient who has previously had a diabetic foot ulcer because if that patient’s neuropathy was sufficient to allow for ulceration once, it would likely do so again.
With regard to claim 26, as noted above Fink discloses foot ulcers.
Response to Arguments
Applicant's arguments filed 04/20/2026 have been fully considered but they are not persuasive.
On page 5, Applicant argues that one having ordinary skill would have only expected capsaicin to be effective as a vasodilator when the body is capable of responding by vasodilation; however, diabetic neuropathy damages the response of the body to things like surface pressure and heat, which would normally result in vasodilation.
The examiner respectfully disagrees that one having ordinary skill would have lacked reasonable expectation that capsaicin would increase blood flow in the skin of a diabetic patient because response to things like surface pressure and heat are dysregulated. As noted in the rejection above, several studies have shown improvement in nerve function and sensation after topical application of an 8% capsaicin patch identical to the patch described in the instant application. Applicant is reminded that conclusive proof of efficacy is not required to show a reasonable expectation of success. OSI Pharm., LLC v. Apotex Inc., 939 F.3d 1375, 1385, 2019 USPQ2d 379681 (Fed. Cir. 2019) ("To be clear, we do not hold today that efficacy data is always required for a reasonable expectation of success. Nor are we requiring ‘absolute predictability of success.’"); Acorda Therapeutics, Inc. v. Roxane Lab., Inc., 903 F.3d 1310, 1333, 128 USPQ2d 1001, 1018 (Fed. Cir. 2018) ("This court has long rejected a requirement of ‘[c]onclusive proof of efficacy’ for obviousness." (citing to Hoffmann-La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331 (Fed. Cir. 2014); PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1364 (Fed. Cir. 2007); Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364, 1367–68 (Fed. Cir. 2007) (reasoning that "the expectation of success need only be reasonable, not absolute")). The examiner considers the fact that capsaicin has improved nerve function in several studies of neuropathy to provide sufficient motivation and expectation of success to try the same topical capsaicin patch in nonpainful neuropathy. Anand indicates that NGF levels return to levels similar to those seen in healthy skin after treatment with the capsaicin 8% patch (0247). This fact too would lead one of ordinary skill to predict nerve healing due to topical exposure to capsaicin. As explained previously on the record in the Office action mailed 04/09/2025, although the molecular mechanism underlying neuropathy [of chemotherapy induced neuropathology] may differ, the effect of capsaicin on the nerve and surrounding tissue should be the same or comparable because the applied formulation, 8% capsaicin patch, is identical (MPEP 2112.01(II): "Products of identical chemical composition cannot have mutually exclusive properties." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).) The examiner acknowledges previous arguments that the environment in the skin tissue of a diabetic patient may differ from the environment in a patient having neuropathy due to cancer chemotherapy. However, the examiner maintains the opinion that one of ordinary skill would have had reasonable expectation of success that capsaicin could restore some function of the nerves/skin of a patient having nonpainful diabetic neuropathy. Evidence of record shows that nerve regeneration following topical capsaicin treatment proceeds more slowly in patients with diabetes than in healthy control subjects in a clinical study (see abstract of Polydefkis, Brain 127, pages 1606-1615; publication year: 2004; cited in the IDS filed 03/03/2023). However, the fact remains that nerve regeneration does occur in the diabetic population in Polydefkis. Moreover, as described in the rejection above, Vinik discloses improved nerve function over standard of care in a subset of individuals having painful diabetic peripheral neuropathy. With Fink’s description of the underlying factors causing diabetic ulcer, which include neuropathy, autonomic dysfunction, and vascular insufficiency all possibly contributing, as well as the prior art teaching that capsaicin is a vasodilator, and can cause restoration of at least some nerve function in CIPN patients and patients with painful diabetic neuropathy, the prior art provides both strong motivation and reasonable expectation of success that treating nonpainful diabetic peripheral neuropathy would be beneficial in terms of health of the tissue, blood flow, and restoration of nerve function. One would have predicted that capsaicin’s effect on nerve regeneration would benefit any type of neuropathy. Additionally, Vinik discloses improved nerve function over standard of care in a subset of individuals having painful diabetic peripheral neuropathy. With Fink’s description of the underlying factors causing diabetic ulcer, which include neuropathy, autonomic dysfunction, and vascular insufficiency all possibly contributing, as well as the prior art teaching that capsaicin is a vasodilator, and can cause restoration of at least some nerve function in CIPN patients and patients with painful diabetic neuropathy, the prior art provides both strong motivation and reasonable expectation of success that treating nonpainful diabetic peripheral neuropathy would be beneficial in terms of health of the tissue, blood flow, and restoration of nerve function.
On pages 5-6 Applicant describes the effect of the claimed method and points out that claim 14 explicitly requires this outcome. Applicant argues further that Fink does not provide indication that minoxidil would fully or partially restore the ability of the skin vasculature to dilate.
In response to applicant's argument that the full or partial restoration of the ability of the skin vasculature to dilate in response to the application of skin surface pressure, chemical stimulants, and/or heat, wherein the full or partial restoration aids prevention of diabetic ulcers, the fact that the inventor has recognized another advantage which would flow naturally from following the suggestion of the prior art cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985).
On page 6, Applicant points to a publication by Anand (Front. Neurol., 10/26/2022), a copy of which has been submitted; however, this document has not been properly cited in an IDS, and therefore has not been formally considered on the record by the examiner. Applicant points out that this publication provides further data indicating that the capsaicin patch restores normal function to the skin via nerve fiber regeneration.
In response, arguments presented by applicant cannot take the place of evidence in the record. See In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984); In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) (“An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness.”).
As noted above, discovery of an underlying mechanism does not render an otherwise obvious method nonobvious. Moreover, the beneficial effect on nerve has been appreciated as of the instant effective filing date: Anand indicates that NGF levels return to levels similar to those seen in healthy skin after treatment with the capsaicin 8% patch (0247).
Moreover, insomuch as this may be an assertion of unexpected results, 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. In the instant case, one having ordinary skill would have expected improvement in nerve physiology, as discussed in the rejection, therefore the result is not unexpected.
On pages 6-7, Applicant argues that the examiner has not addressed the recitation requiring an outcome of fully or partially restoring an ability of skin vasculature to dilate in response to an application of skin surface pressure, chemical stimulants and/or heat of a patient suffering from non-painful diabetic peripheral neuropathy.
As explained in the rejection, the cited prior art renders obvious applying to the skin of a patient suffering from nonpainful diabetic neuropathy a patch identical to the patch described in the instant invention. Applicant’s assertion that the rejection fails to address the limitation regarding restoration of the ability of the skin vasculature to dilate is inaccurate. The restoration of the ability of the skin vasculature to dilate is an outcome intended for the claimed method, and the examiner has established a prima facie case that this outcome would have been inherent.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE PEEBLES whose telephone number is (571)272-6247. The examiner can normally be reached Monday through Friday: 9 am to 3 pm.
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/KATHERINE PEEBLES/ Primary Examiner, Art Unit 1617
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