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 .
Claims 1-17 and 21-25 are pending in the instant application. Claims 15, 16 and 21-25 are rejected. Claims 1-14 and 17 are allowed.
Information Disclosure Statements
The information disclosure statements filed on January 6, 2025 have been considered and signed copies of form 1449 are enclosed herewith.
Claim Rejections - 35 USC §§ 101 & 112
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
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.
Claim 16 is rejected under 35 U.S.C. § 101 because the claimed recitation of a use, without setting forth any steps involved in the process, results in an improper definition of a process, i.e., results in a claim which is not a proper process claim under 35 U.S.C. § 101. See for example Ex parte Dunki, 153 USPQ 678 (Bd. App. 1967) and Clinical Products, Ltd. v. Brenner, 255 F. Supp. 131,149 USPQ 475 (D.D.C. 1966).
Claims 15, 16 and 21-23 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.
Regarding claim 16, the claim is drawn to a use of the compound of formula (I), but since the claim does not set forth any steps involved in the method/process, it is unclear what method/process Applicant is intending to encompass. A claim is indefinite where it merely recites a use without any active, positive steps delimiting how this use is actually practiced.
Regarding claim 15, the phrases "such as for example" and “such as” render the claim indefinite because it is unclear whether the limitations following the phrases are part of the claimed invention. See MPEP § 2173.05(d). This rejection can be overcome, for example, by deleting the phrases and the limitations following them from the claim.
Regarding claim 22, the phrase “e.g.” or "for example" and the word “including” render the claim indefinite because it is unclear whether the limitation(s) following the phrase and word are part of the claimed invention. See MPEP § 2173.05(d). This rejection can be overcome, for example, by deleting the phrase, word and the limitations following them from the claim.
Regarding claims 21, 22 and 23, the claims depend on claim 19, which has been canceled, rendering the claims indefinite. This rejection can be overcome by amending the claims to be independent or by having the claims depend on pending claims.
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 24 and 25 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 a method for treating a disease or disease syndromes, conditions, or symptoms associated with pain and/or inflammation selected from the group consisting of diabetic neuropathic pain, interstitial cystitis/bladder-pain-syndrome, endometriosis and endometriosis-associated pain, does not reasonably provide enablement for a method of treating every known (in the art) disease or disease syndrome, condition, or symptom associated with pain and/or inflammation. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (A)). These include: nature of the invention, breadth of the claims, guidance of the
specification, the existence of working examples, state of the art, predictability of the art
and the amount of experimentation necessary. All of the Wands factors have been
considered with regard to the instant claims, with the most relevant factors discussed
below.
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 in
vitro and in vivo to determine which compounds exhibit the desired pharmacological
activities (i.e., what compounds can treat which specific disease or
disease syndrome, condition, or symptom 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 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 statue. In the instant case, the claimed
invention is highly unpredictable since one skilled in the art would recognize that in
regards to therapeutic effects, whether or not the disease or disease syndrome, condition, or symptom is affected by the inhibition of the Bradykinin B1 receptor would make a difference.
With regards to the treatment of a disease or disease syndromes, conditions, or symptoms associated with pain and/or inflammation, this could include a plethora of diseases, including various broad classes of diseases, such as respiratory diseases, dermatological diseases or conditions, neurodegenerative diseases, etc. (i.e., many of which have a different cause and, therefore, require a different treatment). There is not one class of compounds, let alone one compound, which can treat any disease or disease syndrome, condition, or symptom associated with pain and/or inflammation.
For example, neurodegenerative diseases are associated with inflammation and cover a large array of largely unrelated disorders that have different modes of action and different origins. The term covers such diverse disorders as Alzheimer’s disease, Parkinson’s disease, lewy body dementia, frontotemporal dementia, Huntington’s disease, amyotrophic lateral sclerosis, progressive supranuclear palsy, spinocerebellar ataxias, Pick disease and prion diseases. Current pharmacological therapies offer symptomatic benefits with very little impact, if any, in modifying the course of these diseases. Anticholinesterase drugs are the most frequently used to treat Alzheimer’s disease and levodopa is the most effective pharmacological treatment for Parkinson’s disease. There is no approved pharmacological treatment for most other forms of neurodegenerative diseases except for amyotrophic lateral sclerosis, Huntington disease and some forms of cerebellar ataxias. See abstract of Moraes W. A.S. (Young Perspectives for Old Diseases, 2015, pp. 23-48).
Many of neurodegeneration diseases are genetic. Sometimes the cause is a medical condition such as alcoholism, a tumor, or a stroke. Other causes may include toxins, chemical, and viruses. Sometimes the cause is unknown. See https://medlineplus.gov/degenerativenervediseases.html. In other words, these diseases exhibit a very broad range of effects and origins. Therefore, unlike in some areas of medicine, there is no representative, or "typical" neurodegenerative disorder. Some affect the mind, some affect movement, some affect both, and some affect neither.
Alzheimer's disease and Parkinson’s disease are the most common neurodegenerative disorder. See abstract of Moraes W. A.S. (Young Perspectives for Old Diseases, 2015, pp. 23-48). However, the etiology of Alzheimer’s disease involves both tau protein and 13-amyloid. Such a statement is not true for any other important neurodegenerative disorder, and indeed the vast majority of neurodegenerative disorders involve neither one of those.
Hence, in the absence of a showing of correlation between all the diseases or disease syndromes, conditions, or symptoms associated with pain and/or inflammation claimed as capable of treatment through the inhibition of the Bradykinin B1 receptor, one of skill in the art is unable to fully predict possible results from the administration of the compounds of the claims due to the unpredictability.
The amount of direction or guidance present and the presence or absence of
working examples
A disclosure should contain representative examples which provide reasonable
assurance to one skilled in the art that the compounds which fall within the scope of a
claim will possess the alleged activity. The only direction or guidance present in the instant specification is the listing of diseases or disease syndromes, conditions, or symptoms associated with pain and/or inflammation Applicant considers as treatable by the administration of a cholinate of 2-(1-cyclobutyl-1H-pyrazol-4-yl)-5-[({1-[2-fluoro-2-(trifluoromethyl)phenyl]-cyclopropyl}carbonyl)amino]benzolic acid and reference to WO 2018/114786 A1 (see Example 3) for the synthesis of the compound of formula (I). WO 2018/114786 A1 also discloses the use of the compound (i.e., the non-cholinate form) in various assays (see pages 353-390), including assays drawn to Bradykinin B1 receptor inhibition, endometriosis, peritonitis, diabetic neuropathy, neuropathic pain, arthritis, bladder function, overactive bladder, and Type 2 diabetes. However, the instant specification does not contain any evidentiary support that a cholinate of 2-(1-cyclobutyl-1H-pyrazol-4-yl)-5-[({1-[2-fluoro-2-(trifluoromethyl)phenyl]-cyclopropyl}carbonyl)amino]benzolic acid would be able to treat every known (in the art) disease or disease syndrome, condition, or symptom associated with pain and/or inflammation. Furthermore, there are no working examples to support the treatment of a disease or disease syndromes, conditions, or symptoms associated with pain and/or inflammation.
Applicant has not provided any competent evidence or disclosed tests that are
highly predictive for the pharmaceutical use of the instant compounds and
pharmacological activity in general is a very unpredictable area. Note that in cases
involving physiological activity such as the instant case, "the scope of enablement
obviously varies inversely with the degree of unpredictability of the factors involved."
See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
The level of skill in the art
The level of skill in the art is high. However, due to the unpredictability in the
pharmaceutical art, 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 which compounds exhibit the desired pharmacological activity and which
diseases or disorders would benefit from this activity.
Thus, the specification fails to provide sufficient support of the broad use of the
compounds of the instant claims for the treatment of the various claimed
diseases or disease syndromes, conditions, or symptoms associated with pain and/or inflammation, as a result necessitating one of skill to perform an exhaustive search for which diseases or disease syndromes, conditions, or symptoms associated with pain and/or inflammation can be treated by the compounds of the instant claims in order to practice the claimed invention. Only several of the claimed diseases are discussed here to make the point of an insufficient disclosure, it does not mean that the other diseases or disease syndromes, conditions, or symptoms associated with pain and/or inflammation meet the enablement requirements.
The quantity of experimentation needed
The quantity of experimentation needed is undue experimentation. One of skill in
the art would need to determine what specific diseases or disease syndromes, conditions, or symptoms associated with pain and/or inflammation are benefited by the
administration of the compounds of the instant claims.
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 method. In view of 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.
Genentech Inc. v. Novo Nordisk A/S (CA FC) 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 "patent 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 specific diseases or disease syndromes, conditions, or symptoms associated with pain and/or inflammation can be treated by the compounds encompassed in the instant claims, with no assurance of success.
This rejection can be overcome amending the claims to be drawn to a method for treating a disease or disease syndromes, conditions, or symptoms associated with pain and/or inflammation selected from the group consisting of diabetic neuropathic pain, interstitial cystitis/bladder-pain-syndrome, endometriosis and endometriosis-associated pain.
Allowable Subject Matter
Claims 1-14 and 17 are allowed. No prior art was found. The closest prior art is WO 2018/114786 A1 which discloses the compound 2-(1-Cylcobuty-1H-pyrazol-4-yl)-5-[({1-[2-fluoro-4-(trifluoromethyl)-phenyl]cyclopropyl}carbony)amino]benzoic acid (see Example 3 on page 287) but does not disclose or suggest a cholinate thereof.
Conclusion
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/KRISTIN A VAJDA/Primary Examiner, Art Unit 1622