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 .
Status of the Claims
Clams 1-13 and 16-22 are pending and examined.
Claim of Foreign Priority
While a Certified Copy of Foreign Priority Document has been received by the Office, a claim of Foreign Priority was not included in the Application Data Sheet filed by Applicant. For purposes of examination, the cited prior art precedes the earliest potential priority date claimed.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claim 2 is objected to because of the following informalities: Claim 2 depends from “claim 0” and is therefore improper. The examiner interprets this claims to depend from claim 1 for purposes of examination below. Appropriate correction is required.
Claim Rejections - 35 USC § 112
Regarding claim 10, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
NOTE: The examiner interprets the term surgery to be synonymous with operation. If this is not the case, the examiner requests Applicant change the term surgery to operation or the term postoperative to postsurgical for purposes of consistency and to prevent a rejection for lack of antecedent basis.
The examiner interprets the phrase “associated with” to mean concurrent with and/or caused by for purposes of examination.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-13 and 16-22 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treatment and amelioration of neuropathic pain, does not reasonably provide enablement for prevention of all forms of facial pain, prevention of all forms of postoperative pain, and inhibiting the risk of pain.
The term “treatment” is used in the claims. The instant Specification defines four species of treatment to include: preventive treatment, prophylactic treatment, ameliorative treatment, and symptomatic treatment. See p16-17 Definitions. Per Applicant’s definitions, preventive treatment and prophylactic treatment include administration to a subject that does not have a condition or symptom, but is merely at risk of the same. Claims also include inhibiting risk (i.e., claims 16 and 18). This is in contrast to claims also directed to reducing risk (claim 17). In light of claim differentiation, the examiner interprets inhibiting as preventing and reducing as ameliorating.
Prevents means to totally eliminate and inhibit risk means that there is no longer any chance that pain could occur.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to treat and prevent a subject population having a claimed condition. Treatment of facial pain in a subject diagnosed with facial pain is enabled. Further, ameliorating postsurgical pain in a subject that has undergone or will undergo a surgical procedure is also enabled.
In particular this Scope of Enablement Rejection applies to the following: Preventing and/or inhibiting pain or risk.
As stated in the MPEP 2164.01(a), “There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is "undue."
In In re Wands, 8 USPQ2d 1400 (1988), factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have need described. They are:
1. The nature of the invention
2. The state of the prior art
3. The predictability or lack thereof in the art
4. The amount of direction or guidance present
5. The presence or absence of working examples
6. The breadth of the claims
7. The quantity of experimentation needed, and
8. The level of skill in the art
The Nature of the Invention
The instant claims are drawn to prevention, treatment, and inhibiting the risk of facial pain. Treatment, which is defined by the instant Specification to include “prevention” actually means to anticipate or counter in advance, to keep from happening, etc. and there is no disclosure as to how one skilled in the art can reasonably establish the basis and the type of subject to which the instant compounds and compositions can be administered in order to have the "preventive" effect for a patient suffering or susceptible to facial pain nor the inhibition of risk of pain in a same subject. Example 2 is directed to prophylactic treatment.
The State of the Prior Art and the Predictability or lack thereof in the art
The state of the prior art is that the pharmacological art involves screening invitro and in vivo to determine which compounds exhibit the desired pharmacological activities (i.e. what compounds can treat which specific diseases/conditions by what mechanism). There is no absolute predictability even in view of the seemingly high level of skill in the art. The existence of these obstacles establishes that the contemporary knowledge in the art would prevent and treat one of ordinary skill in the art from accepting any therapeutic regimen on its face.
The instantly claimed invention is highly unpredictable as discussed below: It is noted that the pharmaceutical art is unpredictable, requiring each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F.2d 833, 166 USPQ 18 (CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. In the instant case, the instantly claimed invention is highly unpredictable since one skilled in the art would recognize that in regards to the preventative effects of the instantly claimed compounds on a facial pain disorder and on the inhibition of risk of pain.
According to Cleveland Clinic, https://my.clevelandclinic.org/health/diseases/15833-neuropathic-pain “You can’t always prevent nerve pain from happening.” You can reduce overall risk. People might need a combination of medication and physical therapy and psychological counseling.
According to The Ramos Center for Interventional & Functional Pain Medicine, https://ramoscenter.com/neuropathic-pain/ “Although early treatment is crucial for neuropathic pain management, there is no single treatment available that can cure or prevent neuropathic pain completely.”
With regards to preventing facial pain, there are various conditions that can ultimately cause depression or a neurological condition. Further, because of the broad range of individuals who can be affected by a neurodegenerative disease e.g., prevention of the disease is focused on a person’s risk of the same, which is not entirely predictable. It is known in the art that in order to establish a proper and effective prevention plan for any neurological condition using medication, it is necessary for a practitioner in the art area to establish definitively that a person is at risk for the same. No medications are disclosed in the art as being useful for the general prevention of such conditions without accounting for the particular cause of the disease and the specific patient population.
The Amount of Direction / Guidance Present and the Presence or Absence of Working Examples
The examples in the instant Specification provides a single “Example 2” of a method of prophylactic treatment of pain with compound 1. The method entails an administration to animals at an oral dose of 0.3-3 mg/kg in a rat model of mechanical and thermal hypersensitivity. See p23, lines 31-34. Treatments were administered starting on day 2 and continued once daily from days 3-7.
The working examples are focuses solely on observing a response in rats to specific forms of stimuli without adequate understanding if pain was totally prevented. While treatment and an amelioration appears to be observed, it is not clear what basis there is to conclude all pain was prevented and whether risk was inhibited. A marked reduction of pain thresholds and a significant reduction indicates an analgesic effect.
The level of the skill in the art
The level of skill in the art is high. However, due to the unpredictability in the pharmaceutical art as described above, it is noted that each embodiment of the invention is required to be individually assessed for physiological activity by in vitro and in vivo screening to determine whether the compound exhibits the desired pharmacological activity. The amount of guidance or direction needed to enable the invention is inversely related to the degree of predictability in the art. In re Fisher, 839, 166 USPQ 24. Thus, although a single embodiment may provide broad enablement in cases involving predictable factors, such as mechanical or electrical elements, in cases involving unpredictable factors, such as most chemical reactions and physiological activity, more teaching or guidance is required. In re Fishcher, 427 F.2d 839, 166 USPQ 24; Ex Parte Hitzeman, 9 USPQ 2d 1823.
The quantity of experimentation needed
The quantity of experimentation needed is undue experimentation. One of skill in the art would need to definitively determine the specific population of individuals who would need to be treated and would furthermore have to determine which of the claimed compounds would provide for the prevention and inhibition of pain and risk of pain. To make such determination in any patient population with facial pain of all types, as the instant claims are drawn to, would require undue experimentation to both develop an animal model which would reasonably correlate with all forms of pain and also to identify the portion of the population in which the instantly claimed compounds would need to necessarily be administered.
According to Cleveland Clinic (11/13/2023), https://my.clevelandclinic.org/health/diseases/15833-neuropathic-pain “You can’t always prevent nerve pain from happening.” You can reduce overall risk. People might need a combination of medication and physical therapy and psychological counseling.
According to The Ramos Center for Interventional & Functional Pain Medicine, https://ramoscenter.com/neuropathic-pain/ “Although early treatment is crucial for neuropathic pain management, there is no single treatment available that can cure or prevent neuropathic pain completely.”
Thus, factors such as "sufficient working examples", "the level of skill in the art" and "predictability", etc. have been demonstrated to be sufficiently lacking in the instantly claimed methods. In view of the breadth of the claim, the chemical nature of the invention, and the lack of working examples regarding the activity of the claimed compounds, one having ordinary skill in the art would have to undergo an undue amount of experimentation to use the invention commensurate in scope with the claims.
The court in Genentech Inc. v. Novo Nordisk A/S (CAFC) 42 USPQ2d 1001, states that, “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion" and "[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable.”
Therefore, in view of the Wands factors and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, a person of skill in the art would have to engage in undue experimentation to test which diseases can be treated or prevented by the compound encompassed in the instant claims, with no assurance of success.
To overcome this rejection, limit the claims to treating pain in a subject experiencing facial pain, e.g., and mitigating or ameliorating postsurgical pain a subject that has or will undergo a surgical procedure by administering the claimed agent to the subject 4 days prior to said surgery, e.g.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-13 and 16-22 are rejected under 35 U.S.C. 103 as being unpatentable over Nielsen et al., (WO2020/053377 A1) (cited in ISR), in view of Xie et al., (US2016/0347810), in view of Piomelli et al., (US2009/0082435), in view of Vickers et al., “Neuropathic Orofacial Pain Part 1- Prevalence and Pathophysiology,” Australian Endodontic Journal February 11, 2010 (Abstract).
Nielson teaches treatment of neuropathic pain with the claimed compound. See Abstract. The compound can treat pain, neuropathic pain, and/or itch. See p1, lines 7-8. The compound can be used to prevent, treat, and alleviate neuropathic pain. See p3, lines 12-13. Compositions may be administered orally as well as buccally and sublingually, and by inhalation, e.g. See p7-8, bridging par. An oral dose can range from 1 microgram or .001 mg to 100 mg/kg/day orally. See p9, lines 28-29. Symptoms of neuropathic pain including burning, tingling, electricity, pins and needles, hyperalgesia, and many other characterizations. See p10, lines 23-28. Administration of an API is taught after surgery. Further, chronic administration of was shown to maintain effects indicating a lack of tolerance. See Figure 3, e.g. It is not apparent that the type of surgery would impact the ability to mitigate and/or treat pain and itch resulting therefrom.
With regard to claims directed to administration for a number of days prior to an operation, the examiner notes that Nielson teaches after 7 days of chronic treatment, a significant analgesic effect of all doses tested was maintained. As such, when prevention is intended, a starting point for dosage regimen optimization would be considered to be 7 days prior to surgery, e.g. Chronic and acute administration are both effective. See Example 4, among others.
Nielson does not teach facial pain in particular.
Xie teaches neuropathic pain to include: trigeminal neuralgia (par. 92), postoperative pain (prior claim 16); and migraine or tension headache (par. 189).
Piomelli teaches neuropathic pain to include: trigeminal neuralgia, post-surgical pain, atypical facial neuralgia after tooth extraction, mononeuropathy, and others. See par.’s 19 and 48.
Vickers teaches orofacial pain is neuropathic pain and those predisposed may include those suffering from cluster or migraine headaches. See Abstract. This is common at the dentist and is common after endodontic treatments.
It would have been prima facie obvious to a person having ordinary skill in the art prior to the filing of the instant application to arrive at the claimed methods in view of Nielson, Xie, Piomelli, and Vickers. One would be motivated to do so because the claimed API is taught to treat neuropathic pain at claimed dosages and through a same route of administration. Moreover, Xie, Piomelli, and Vickers collectively teach that trigeminal neuralgia, postoperative pain, atypical facial neuralgia, orofacial pain, migraines, and tension headaches are forms of neuropathic pain. As such, a POSA would have a reasonable and predictable expectation of success in treating the forms of facial pain and neuropathic pain by administering an agent known to treat neuropathic pain at dosages taught to prevent and treat neuropathic pain when administered by a claimed route of administration at a claimed dosage.
As such, no claim is allowed.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JARED D BARSKY whose telephone number is (571)272-2795. The examiner can normally be reached on 9-5 M-F.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy Clark can be reached on 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JARED BARSKY/Primary Examiner, Art Unit 1628