Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
DETAILED ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 Request for Continued Examination (RCE) filed March 12, 2026, with the submission filed on January 13, 2026, that includes a response to the Final Office Action mailed November 12, 2025, has been entered. Claims 13 and 15 have been amended; and claims 1-12, 14, 16, and 21-35 have been canceled. Claims 15 and 18 have been withdrawn. Claims 13, 17, 19, and 20 are under examination in the application.
Withdrawal of Prior Claim Rejections - Obviousness-Type Double Patenting
A terminal disclaimer with respect to U.S. Patent No. 11,654,110 has been timely filed in compliance with 37 CFR 1.321(c) or 1.321(d), and signed in compliance with 37 CFR 1.321(b). Therefore, the Obviousness-Type Double Patenting rejection presented in the Final Office Action mailed November 12, 2025 is hereby withdrawn.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 13, 16, 17, and 19-21 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 13 is indefinite for the following reasons:
1. Claim 13 is directed to “determining whether an injured peripheral nerve has capacity for recovery”, requires administering an agent that promotes transient peripheral nerve activity in nerves that have “a capacity for improving their activity”, then requires detecting transient peripheral nerve activity, which indicates “capacity for recovery”. One of ordinary skill in the art thus cannot definitively ascertain the metes and bounds of the claimed subject matter. Is the peripheral nerve one that has “a capacity for recovery” or rather has “a capacity for improving their activity”? Are these two expressions for the very same thing? Moreover, “improving their activity” is a relative expression not defined by the claim. Improving in what way, and against what baseline or standard?
2. Claim 13 is directed to “determining whether an injured peripheral nerve has capacity for recovery”, and requires administering 4-AP that promotes transient peripheral nerve activity, and detecting the presence or absence of “one or more characteristics” of transient peripheral nerve activity in response to the 4-AP, wherein the presence of transient peripheral nerve activity indicates the injured peripheral nerve has “capacity for recovery”. So, in short, one administers 4-AP that stimulates transient nerve activity, and if the 4-AP in fact does stimulate the transient nerve activity, then the nerve has a “capacity for recovery”. One of ordinary skill in the art cannot definitively ascertain the metes and bounds of “capacity for recovery”. Recovery of what? If the 4-AP is stimulating transient nerve activity in the nerve like it supposed to, then it would appear that the nerve is functioning just as it should. So, what then needs to be “recovered”? Moreover, does a “capacity for recovery” necessarily mean an actual recovery, or just a “possibility for recovery”? Not only is what is being recovered an unknown, whether the recovery is actually attained also appears to be an unknown. Therefore, the metes and bounds of “a capacity for recovery” is indefinite.
3. Claim 13 also appears to equate “a capacity for recovery” with the ability of 4-AP to “promote transient peripheral nerve activity”. However, the actual, concrete presence of a direct correlation to actual recovery is rather arbitrary. For example, a given amount of 4-AP may in fact successfully stimulate transient peripheral nerve activity in the injured nerve of one subject, but that subject never actually recovers, while the very same amount of 4-AP may not stimulate transient peripheral nerve activity in the injured nerve of another subject, but that other subject actually recovers. One of ordinary skill in the art cannot definitively ascertain whether a “capacity to recover” must somehow be manifest in an actual, concrete recovery, or whether there is no necessary correlation between a “capacity to recover” and actual, concrete recovery.
4. Moreover, the claim does not expressly limit the amount of 4-AP that must be administered, and one of ordinary skill in the art cannot definitively ascertain whether the amount of 4-AP that stimulates transient peripheral nerve activity in the injured nerve is the same or not from the amount that stimulates transient peripheral nerve activity in an uninjured nerve. If the amount of 4-AP that stimulates transient peripheral nerve activity in an uninjured nerve does not stimulate transient peripheral nerve activity in an injured nerve, but a significantly higher amount of 4-AP is able to stimulate transient peripheral nerve activity in the injured nerve, does this meet the “capacity for recovery” limitation? One of ordinary skill in the art thus cannot definitively ascertain the metes and bounds of the claimed subject matter.
***For examination, the claim is being interpreted as merely requiring administration of an arbitrary amount of 4-AP to the subject with an injured peripheral nerve, and then simply detecting whether there is transient peripheral nerve activity in response to this stimulus. There need not be any actual recovery, or even any actual “capacity to recover”. In other words, an arbitrary amount of 4-AP is administered, and there is an attempt to measure peripheral nerve activity, and there can either be a detected response or no detected response in peripheral nerve activity, and that’s it.
Claims 17, 19, and 20 are indefinite for depending from an indefinite claim.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 13, 17, 19, and 20 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Shi et al. (Neurosci. Bull. 2011; 27(1): 36-44), in view of Ouyang et al. (J Neurotrauma. 2010; 27: 1109-1120), and Novak et al. (J Hand Therapy. 2005; 18(2): 230-240).
Applicant Claims
Applicant’s elected subject matter is directed to a method for “determining” whether an injured nerve has “capacity for recovery” comprising systemically administering 4-aminopyridine to a subject with an injured peripheral nerve, and “detecting” by physical examination one or more “characteristics” of transient peripheral nerve activity; wherein the injured peripheral nerve is a crushed peripheral nerve.
Determination of the Scope of the Prior Art (MPEP §2141.01)
Shi et al. disclose that acute nerve trauma, such as by compression, can displace myelin, that the demyelination of axons can lead to axonal conduction block mediated by potassium channels, and that systemically or locally administered 4-aminopyridine can successfully restore axonal conduction in demyelinated peripheral and central nerves and promote recovery of neurological function.
Ouyang et al. disclose that nerve crush/compression injury in particular can trigger demyelination and axonal conduction block mediated by potassium channels, manifested in a decline of the compound action potential, and that 4-aminopyridine can successfully restore axonal conduction, including restoring the compound action potential to near pre-injury levels. Moreover, nerve activity, e.g. via the compound action potential, can be monitored in real time after nerve crush injury, at any period before the application of 4-aminopyridine, during exposure to 4-aminopyridine, and/or after washout of 4-aminopyridine.
Novak et al. disclose that nerve activity can be monitored after crush/compression injury by various means, including by physical examination.
Ascertainment of the Difference Between the Scope of the Prior Art and the Claims (MPEP §2141.02)
Shi et al. do not explicitly disclose detecting peripheral nerve activity during exposure to 4-aminopyridine by physical examination. This deficiency is cured by the teachings of Ouyang et al. and Novak et al.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been prima facie obvious for one of ordinary skill in the art at the time the present application was filed to combine the respective teachings of Shi et al., Ouyang et al. and Novak et al., outlined supra, to devise Applicant’s claimed method.
Shi et al. disclose that nerve compression injury can displace myelin, that the demyelination of axons can lead to axonal conduction block mediated by potassium channels, and that systemically or locally administered 4-aminopyridine can successfully restore axonal conduction in demyelinated peripheral and central nerves and promote recovery of neurological function. Since Ouyang et al. disclose that the axonal conduction block in nerve crush/compression injury can be “detected” by a decline of the compound action potential, and that 4-aminopyridine can successfully restore axonal conduction, which restoring of nerve activity can be “detected” by the compound action potential being restored to near pre-injury levels, and that nerve activity can be monitored “live” at any time after nerve crush injury, i.e. before, during or after the application of 4-aminopyridine; and since Novak et al. disclose that nerve activity can be monitored after crush/compression injury by various means, including by physical examination; one of ordinary skill in the art would thus be motivated to systemically administer 4-aminopyridine to a subject with a crushed peripheral nerve, and “detect” by physical examination the manifestation of an increase in the peripheral nerve activity caused by administration of 4-aminopyridine, with the reasonable expectation that the resulting method will restore axonal conduction and promote recovery of nerve function after crush injury.
In light of the foregoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103(a).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Response to Arguments
Applicant's arguments filed January 13, 2026 have been fully considered but they are not persuasive.
i) Applicant contends that the cited prior art “fail to disclose or suggest using 4-AP to test whether an injured peripheral nerve…is capable of improving from the injury”.
The Examiner, however, would like to point out the following:
1. First, it is noted that “capable of improving from the injury” is indefinite, for reasons discussed under 35 USC 112, supra.
2. Applicant is basically administering 4-AP to an injured nerve, and then detecting the presence of a response to the 4-AP, if any. The nerve need not respond at all to the 4-AP. Further, even if the nerve responds to the 4-AP, there is some sort of determination made as to whether there is a “capacity for recovery” or “capacity for improving”, whatever that really means. Presumably, a “capacity for” merely means a probability or a possibility, and nothing more. In effect, it would appear that if the injured nerve is still alive, it will or at least could be made to (e.g. by a very large dose) respond to the application of 4-AP, thus indicating the nerve is not yet completely dead. If the nerve is still alive, it thus has the “capacity for recovery”.
3. While the cited prior art does not precisely disclose Applicant’s claims verbatim, one of ordinary skill in the art would be familiar with the application of 4-AP to nerves, and would know that 4-AP application to injured nerves successfully restores axonal conduction, including restoring the compound action potential to near pre-injury levels. If the action potential can be restored, nerve activity is restored. Shi expressly discloses that 4-AP restores axonal conduction and neurological function of demyelinated axons in both central and peripheral nerves alike. As Shi expressly states, “4’AP” is “a leading choice of potassium channel blocker to restore axonal conduction in demyelinated peripheral and central nervous system nerves” (see Shi, page 38, left column, highlight added for clarity). Hence, in the case of a mechanical injury to nerve, the demyelination that results facilitates an axonal conduction block, and this axonal conduction block can be restored by application of 4-AP, regardless if the nerve is central or peripheral. Despite the known differences in the myelination of the central nerves vs the peripheral nerves, the phenomenon at issue here, i.e. conduction block in injured, demyelinated nerves, and the ability of 4-AP to restore conduction block in these nerves, is common and essentially the same in both central nerves and peripheral nerves. Applicant has provided no evidence to the contrary.
4. The basic premise of the presently claimed method is to systemically administer 4-AP to a subject with an injured peripheral nerve (i.e. the stimulus), and then detect/determine if there is, in fact, transient activity in the injured peripheral nerve (i.e. the response). That’s really about it. The claim does not require any transient activity in the peripheral nerve in response to the application of the 4-AP. The final part of the claimed subject matter is essentially an abstraction, i.e. really nothing more than a mental conclusion whether the injured peripheral nerve has “a capacity for recovery” depending upon whether transient nerve activity is detected or not. As noted, supra, “a capacity for recovery” is indefinite, the claim does not define what, precisely, is being recovered, and there appears to be no requirement for any actual, concrete recovery. A “capacity for recovery”, even if deemed present, does not necessarily mean an actual “recovery” of anything.
5. Ouyang discloses that the axonal conduction block in nerve crush/compression injury can be “detected” by a decline of the compound action potential, and that 4-aminopyridine can successfully restore axonal conduction, which restoring of nerve activity can be “detected” by the compound action potential being restored to near pre-injury levels, and that nerve activity can be monitored “live” at any time after nerve crush injury, i.e. before, during or after the application of 4-aminopyridine. Novak discloses that nerve activity can be monitored after crush/compression injury by various means, including by physical examination. Again, Applicant is merely systemically administering 4-AP to a subject with a peripheral nerve injury, and then detecting/determining whether there is any transient activity in the injured peripheral nerve, i.e. whether the 4-AP is able to unblock the nerve conduction. One of ordinary skill in the art is one of ordinary creativity, not an automaton. This is without question within the capacity of the ordinary mechanic in the art, i.e. administer 4-AP to a subject with a peripheral nerve injury, and then detect/determine whether there is any transient activity in the injured peripheral nerve, i.e. whether the 4-AP is able to unblock the nerve conduction, and if it can the nerve is still viable, and if the nerve is still viable it has “a capacity for recovery”. This is clearly not a patentable advance in the art. The active steps are obvious, and the outcome is predictable. There is simply no patentable advance here.
For the foregoing reasons, the 35 USC 103 rejection is hereby maintained.
Conclusion
No claims are allowed.
Inquiries
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID BROWE whose telephone number is (571)270-1320. The examiner can normally be reached Monday - Friday, 9:30 AM to 6 PM EST.
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/DAVID BROWE/Primary Examiner, Art Unit 1617
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