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
Claims 1-14, 17, and 21 are pending.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55. Instant application is a continuation of PCT/EP2021/070310, filed 07/21/2021. PCT/EP2021/070310 claims priority of foreign application EP20187298.3, filed 07/23/2020. Therefore, the effective filing date is 07/23/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/12/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claims 1-5, 9, 10, 13, 17, and 21 are objected to because of the following informalities:
Claims 1-3 read “R is … substituted with H, halogen, alkyl, haloalkyl, cyano and hydroxyl” (emphasis added), and should read “R is … substituted with H, halogen, alkyl, haloalkyl, cyano, or hydroxyl”. Alternatively, the claims could read “R is … substituted with one or more substituents selected from the group consisting of H, halogen, alkyl, haloalkyl, cyano, and hydroxyl”.
Claims 2-4 read “…1-to-4 N and 0-to-1 O, unsubstituted or substituted…” and should read “…1 to 4 nitrogen atoms and 0 to 1 oxygen atoms, wherein the heteroaryl ring is unsubstituted or substituted…” for clarity.
Claims 5, 9, and 10 read “…comprising 1 N and 1 O either unsubstituted or substituted with methyl, or unsubstituted heteroaryl ring comprising 1-to-4 N.” and should read “…comprising 1 nitrogen and 1 oxygen, wherein the 5-membered heteroaryl is either unsubstituted or substituted with methyl, or wherein R is an unsubstituted heteroaryl ring comprising 1 to 4 nitrogen atoms.” for clarity.
Claim 13 reads “The compound according to claim 1” (emphasis added) and should read “A compound according to claim 1” for consistency with claim 12.
The numbering of claims 17 and 21 reads “17)” and “21)”, respectively, and for consistency should read “17.” and “21.”.
The numbering of claims does not include claims 15, 16, or 18-20, or mention these claims as canceled. The numbering of claims should include all claims 1-21 to avoid confusion.
Claim 21 reads “A method for …, which method comprises administering…” and for clarity and brevity should read “A method for… comprising administering…”.
Appropriate correction is required.
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.
Claim 21 is 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 inhibiting V1a receptors comprising administering a compound of formula (I), does not reasonably provide enablement for the therapeutic and/or prophylactic treatment of conditions listed in instant claim 21. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
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. These factors include, but are not limited to: (a) breadth of the claims; (b) nature of the invention; (c) state of the prior art; (d) level of one of ordinary skill in the art; (e) level of predictability in the art; (f) amount of direction provided by the inventor or joint inventor; (g) existence of working examples; and (h) quantity of experimentation needed to make or use the invention based on the content of the disclosure. {See Ex parte Forman 230 USPQ 546 (Bd. Pat. App. & Inter. 1986); and In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988)}.
The above factors, regarding the present invention, are summarized as follows:
Breadth of the claims
The breadth of the claim includes a method of treating a condition characterized by inappropriate secretion of vasopressin in a patient, comprising administering a compound of the formula (I).
Nature of the invention
The nature of the invention is performance of a method of treating a condition characterized by inappropriate secretion of vasopressin in a patient, comprising administering a compound of general formula (I).
State of the prior art
No single drug has been discovered that is effective in treating the myriad of conditions which are claimed to be treated by the instant compounds, including, but not limited to, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, aggressive behavior, social anxiety disorder, post-traumatic stress disorder (PTSD), brain edema in stroke or traumatic brain injury, phase shift sleep disorders, “small cell lung cancers or breast cancers; hyponatremic encephalopathy; pulmonary syndrome; Meniere's disease; ocular hypertension; glaucoma; cataracts; obesity; type-I and type-II diabetes; atherosclerosis; metabolic syndrome; hyperlipidemia; insulin resistance; or hypertriglyceridemia; in5 pos-operative treatments, in particular after abdominal surgery; autism; hypercortisolemia; hyperaldosteronemia; pheochromocytoma; Cushing's syndrome; preeclampsia; disorders of micturition” (page 18 of the specification), “ACTH-dependent disorders, cardiac disorders, pain, modifications in gastric emptying, in fecal excretion (colitis, irritable bowel syndrome or Crohn's disease) or in acid secretion, hyperglycemia, immunosuppression, inflammatory processes (rheumatoid arthritis and osteoarthritis), multiple infections, septic shock, cancers, asthma, psoriasis and allergies” (page 17 of the specification). See In re Hokum, 226 USPQ 353 (ComrPats 1985).
Level of one of ordinary skill in the art
The artisans performing the inventor’s or joint inventor’s method of treating a condition characterized by inappropriate secretion of vasopressin in a patient, comprising administering a compound of formula (I), would be a collaborative team of synthetic chemists and/or health practitioners, possessing commensurate degree level and/or skill in the art, as well as several years of professional experience.
Level of predictability in the art
Synthetic organic chemistry is quite unpredictable. See In re Marzocchi and Horton 169 USPQ at 367 ¶3. Similarly, it is well established that “[T]he scope of enablement varies inversely with the degree of unpredictability of the factors involved, and physiological activity is generally considered to be an unpredictable factor”. See In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970).
Amount of direction provided by the inventor
The invention lacks direction with respect to making and/or using (performing) a method of treating a condition characterized by inappropriate secretion of vasopressin in a patient, comprising administering a compound of formula (I).
Existence of working examples
The disclosure is insufficient to allow extrapolation of the limited examples to enable performing the instantly recited method of treating a condition characterized by inappropriate secretion of vasopressin in a patient, comprising administering a compound of formula (I).
Similarly, according to the specification, compounds of formula (I) are capable of treating a variety of conditions, including, but not limited to, anxiety, depressive disorders, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, aggressive behavior, social anxiety disorder, post-traumatic stress disorder (PTSD), brain edema in stroke or traumatic brain injury, phase shift sleep disorders, “small cell lung cancers or breast cancers; hyponatremic encephalopathy; pulmonary syndrome; Meniere's disease; ocular hypertension; glaucoma; cataracts; obesity; type-I and type-II diabetes; atherosclerosis; metabolic syndrome; hyperlipidemia; insulin resistance; or hypertriglyceridemia; in5 pos-operative treatments, in particular after abdominal surgery; autism; hypercortisolemia; hyperaldosteronemia; pheochromocytoma; Cushing's syndrome; preeclampsia; disorders of micturition” (page 18 of the specification), “ACTH-dependent disorders, cardiac disorders, pain, modifications in gastric emptying, in fecal excretion (colitis, irritable bowel syndrome or Crohn's disease) or in acid secretion, hyperglycemia, immunosuppression, inflammatory processes (rheumatoid arthritis and osteoarthritis), multiple infections, septic shock, cancers, asthma, psoriasis and allergies” (page 17 of the specification).
However, the specification fails to set forth any convincing in vitro and/or in vivo assays corroborating the alleged activity in association with any of the aforementioned diseases. The specification only provides an example to demonstrate the ability of the compounds in the inhibition of V1a receptors. There is insufficient disclosure to reasonably conclude that the method of treating any of the above listed conditions, comprising administering a compound of formula (I), as recited, would contribute to treatment or prophylaxis of any the aforementioned diseases. The inventor or joint inventor has neither provided convincing data for any patient population, nor indicated any art recognized correlation between the disclosed data and the breadth of the claim.
Quantity of experimentation needed
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the invention was filed, would not have taught one skilled in the art how to make and/or use (perform) the full scope of the claimed invention without undue experimentation. See In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993).
One skilled in the art, such as a medical doctor, would be required to perform hundreds of clinical trials and in vivo or in vitro assays in order to determine which of the compounds of formula (I) would be capable of treating which conditions characterized by inappropriate secretion of vasopressin.
The determination that undue experimentation would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the above noted factual considerations. See In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404. These factual considerations are discussed comprehensively in MPEP § 2164.08 (scope or breadth of the claims), § 2164.05(a) (nature of the invention and state of the prior art), § 2164.05(b) (level of one of ordinary skill), § 2164.03 (level of predictability in the art and amount of direction provided by the inventor or joint inventor), § 2164.02 (the existence of working examples) and § 2164.06 (quantity of experimentation needed to make or use the invention based on the content of the disclosure).
Based on a preponderance of the evidence presented herein, the conclusion that the inventor or joint inventor is insufficiently enabled for a method of treating a condition characterized by inappropriate secretion of vasopressin in a patient, comprising administering a compound of formula (I), is clearly justified.
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 14 and 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 14 recites the limitations "formula 4" and “formula 5” in lines 2-3 of the claim. There is insufficient antecedent basis for this limitation in the claim.
Regarding claim 21, the phrase "in particular" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
The inventor or joint inventor should note that claim 21 is a reach-through claim. The claim attempts to obtain protection for subject matter that is prophetic and/or has yet to be invented. Similarly, the metes and bounds of the treatable “conditions of inappropriate secretion of vasopressin” are not defined by the claim, the specification does not provide an adequate standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the metes and bounds of the invention. The specification, on pages 11, uses open language, such as “such as” and “include but are not limited to”, to define “conditions of inappropriate secretion of vasopressin” as “disorders of stress, mood, and behavioral disorders, including stress-related affective disorders, … cardiovascular conditions, for example hypertension, pulmonary hypertension, cardiac insufficiency, myocardial infarction or coronary vasospasm, in particular in smokers, Raynaud's syndrome, unstable angina and 20 PT (percutaneous transluminal coronary angioplasty), cardiac ischemia, hemostasis disturbances or thrombosis; conditions of the central nervous system, such as migraine, cerebral vasospasm, cerebral hemorrhage, trauma and cerebral edema, depression, anxiety, stress, emotional disorders, obsessive- compulsive disorder, panic attacks, psychotic states, aggression, memory or sleep disorders, or cognitive disorders, for example disorders associated with impaired social cognition (e.g., schizophrenia, autism spectrum disorder); conditions of the renal system, such as renal vasospasm, necrosis of the renal cortex, nephrogenic diabetes insipidus or diabetic nephropathy; or conditions of the gastric system, such as gastric vasospasm, cirrhosis of the liver, ulcers or the pathology of vomiting, for example nausea, including nausea due to chemotherapy, or travel sickness; circadian rhythm-related disorders such as phase shift sleep disorders, jet-lag, sleep disorders and other chronobiological disorders, … neuropsychiatric disorders, neuropsychiatric symptoms in neurodegenerative diseases, PTSD, inappropriate aggression, anxiety, depressive disorders, major depression, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior, and other affective disorders”.
However, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments, including, but not limited to, “disorders of stress, mood, and behavioral disorders, including stress-related affective disorders, … cardiovascular conditions, for example hypertension, pulmonary hypertension, cardiac insufficiency, myocardial infarction or coronary vasospasm, in particular in smokers, Raynaud's syndrome, unstable angina and 20 PT (percutaneous transluminal coronary angioplasty), cardiac ischemia, hemostasis disturbances or thrombosis; conditions of the central nervous system, such as migraine, cerebral vasospasm, cerebral hemorrhage, trauma and cerebral edema, depression, anxiety, stress, emotional disorders, obsessive- compulsive disorder, panic attacks, psychotic states, aggression, memory or sleep disorders, or cognitive disorders, for example disorders associated with impaired social cognition (e.g., schizophrenia, autism spectrum disorder); conditions of the renal system, such as renal vasospasm, necrosis of the renal cortex, nephrogenic diabetes insipidus or diabetic nephropathy; or conditions of the gastric system, such as gastric vasospasm, cirrhosis of the liver, ulcers or the pathology of vomiting, for example nausea, including nausea due to chemotherapy, or travel sickness; circadian rhythm-related disorders such as phase shift sleep disorders, jet-lag, sleep disorders and other chronobiological disorders, … neuropsychiatric disorders, neuropsychiatric symptoms in neurodegenerative diseases, PTSD, inappropriate aggression, anxiety, depressive disorders, major depression, obsessive compulsive disorder, autistic spectrum disorders, schizophrenia, and aggressive behavior, and other affective disorders”. Consequently, the method for the treatment or prophylaxis of a condition of inappropriate secretion of vasopressin, the method comprising administering a compound of formula (I), has been rendered indefinite by the use of the reach-through protocol.
Allowable Subject Matter
Claims 6-8, 11, and 12 are allowed. Claims 1-5, 9, 10, 13, and 17 are objected to but appear allowable if the minor informalities are amended.
The closest prior art is WO 2006123242 A1, cited by Applicant in the IDS, which teaches compounds of formula (I), shown below.
PNG
media_image1.png
116
229
media_image1.png
Greyscale
These compounds are taught to be used in the treatment of a disorder for which a V1a antagonist is indicated. These compounds differ from the instantly claimed compounds in that ring A is a heterocycle and not a cyclohexyl as in the instant claims. Additionally, there is the absence of a -CH2- group between R1 and the triazole ring in the prior art compared to the instant compounds. This reference does not teach or suggest the changes that must be made to compounds of formula (I) shown above in order to arrive at the instantly claimed compounds.
Conclusion
Claims 6-8, 11, and 12 are allowed.
Claim 1-5, 9, 10, 13, and 17 is objected to.
Claims 14 and 21 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RILLA M SAMSELL whose telephone number is (703)756-5841. The examiner can normally be reached Monday-Friday, 9-5.
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, Jeffrey Murray can be reached at (571) 272-9023. 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.
/R.M.S./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624