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 .
Priority
This application filed on 09/13/2024, is a national stage application filed under 35 U.S.C. § 371 of international application No. PCT/US2023/064347, filed on 03/14/2023, which claims priority to, and the benefit of, U.S. Provisional Application Ser. No. 63/269,304, filed on 03/14/2022.
DETAILED ACTION
The preliminary amendment filed on 09/13/2024 that amended claims 6-10, and cancelled claim 12, has been acknowledged.
Claims 1-11 are pending.
Claim interpretation
Examination requires claim terms first be construed in terms in the broadest reasonable manner during prosecution as is reasonably allowed in an effort to establish a clear record of what applicant intends to claim. See MPEP § 2111. Under a broadest reasonable interpretation, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. See MPEP § 2111.01. It is also appropriate to look to how the claim term is used in the prior art, which includes prior art patents, published applications, trade publications, and dictionaries. MPEP § 2111.01 (III). However, specific embodiments of the specification cannot be imported into the claims, particularly where the subject claim limitation is broader than the embodiment. MPEP § 2111.01(II).
Claim interpretation for “central nervous system disorders”
Claim 10 and 11 recite “a method for the treatment or prophylaxis of a central nervous system disorder …”. Instant specification describes the term central nervous system as:
“… wherein the central nervous system disorder is a disorder selected from a group consisting of obesity, anxiety (including general anxiety, social anxiety, and panic disorders), depression (for example refractory depression and MDD), psychosis (including psychosis associated with dementia, such as hallucinations in advanced Parkinson's disease or paranoid delusions), schizophrenia, sleep disorders (particularly sleep disorders associated with schizophrenia and other psychiatric and neurological diseases), sexual disorders, migraine, pain and conditions associated with pain, including cephalic pain, idiopathic pain, chronic pain (such as moderate to moderately severe chronic pain, for example in patients requiring 24 hour extend treatment for other ailments), neuropathic pain, dental pain, fibromyalgia, chronic fatigue, agoraphobia, social phobias, agitation in dementia (e.g., agitation in Alzheimer's disease), agitation in autism and related autistic disorders, gastrointestinal disorders such as dysfunction of the gastrointestinal tract motility, and dementia, for example dementia of Alzheimer's disease or of Parkinson's disease; mood disorders; drug dependencies, for example, opioid dependency and/or alcohol dependency, and withdrawal from ding or alcohol dependency (e.g., opioid dependency); opioid overdose; co-morbidities associated with drug dependencies, such as depression, anxiety and psychosis; binge eating disorder; and obsessive- compulsive disorder (OCD), obsessive-compulsive personality disorder (OCPD)and related disorders; or opioid use disorder (OUD), or any combination thereof; …” [page 16, [00042]].
The claimed term central nervous system is interpreted as described by the specification, to include all the recited disorders and conditions.
Claim interpretation for “substantially”
Claims 6 recites “… wherein the compound is substantially free of …”, and claim 7 recites “substantially pure …”. Instant specification described the term substantially free as
"substantially free" means having less than 10 wt.%, or less than 8 wt.%, or less than 6 wt.%, or less than 5 wt.%, or less than 4 w.%, or less than 3 wt.%, or less than 2 wt.%, or less than 1 wt.%, of the isomer which the compound is substantially free of [page 6].
Instant specification described the term and substantially pure as:
a substantially pure diastereomer of the compound of Formula 1B, e.g., having not more than 5 mol% of the Compound of Formula lA, e.g., not more than 4 mol%, or not more than 3 mol%, or not more than 2 mol%, or not more than 1 mol%, or not more than 0.5 mol%, or not more than 0.25 mol%, or not more than 0.15 mol%, or not more than 0.1 mol%, or not more than 0.05 mol%, or not more than 0.01 mol%, of the Compound of Formula lA, measured from the total amount of Compound of Formula I (i.e., not taking into account any compounds other than the Compound of Formula lA and 1B).” [page 7].
Thus, the terms “substantially free” and “substantially pure” are interpreted as described by instant specification.
Abstract
The Abstract of the disclosure is objected to because the Abstract recites “the invention relates to a particular enantiomer …”. Applicant is reminded of the proper language and format for an abstract of the disclosure. The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Rejections 35 U.S.C. 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.
Claims 1-11 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.
Pursuant to 35 U.S.C. 112(b), the claim must apprise one of ordinary skill in the art of its scope so as to provide clear warning to others as to what constitutes infringement. MPEP 2173.02(II); Solomon v. Kimberly-Clark Corp., 216 F.3d 1372, 1379, 55 USPQ2d 1279, 1283 (Fed. Cir. 2000).
Claim 1-9 recite examples in the claims. Claim 1 recites: “Formula I having trans-stereochemistry across the 6b-10a ring fusion, in free or salt form (e.g., pharmaceutically acceptable salt form), for example in an isolated or purified free or salt form (e.g., pharmaceutically acceptable salt form), claim 2 recites “(e.g., pharmaceutically acceptable salt form)”, claim 3 recites “e.g., a 50:50 molar ratio”, claim 4 recites “e.g., at least 55 mol% … i.e., not taking into account…”, claim 5 recites “e.g., at least 55 mol% … i.e., not taking into account…”, etc. As provided in MEMP 2173.05(d), “Description of examples or preferences is properly set forth in the specification rather than the claims. If stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim. In those instances where it is not clear whether the claimed narrower range is a limitation, a rejection under 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph should be made. The examiner should analyze whether the metes and bounds of the claim are clearly set forth. Note that the mere use of the phrase "such as" or "for example" in a claim does not by itself render the claim indefinite. Because independent claim 1 is rejected as being indefinite, dependent claims 10-11 are indefinite due to their dependence on a rejected claim and lacking any limitations that cure the ambiguities resulting from the parent claim(s).
Claim 6 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite. Claim 6 recites “… wherein the compound is substantially free of any of the compound of Formula A, … wherein the compound is substantially free of any of the compound of Formula B, …”. Claim 1 recites Formula I. There is no recitation in claim 1 of Formula A or Formula B. The recitation of “the Formula A and the Formula B” lacks antecedent basis. It appears that Applicant is referring to Formula A and Formula B recited on page 3 of instant specification, however, as provided in the MPEP 2173.05, “Although a claim should be interpreted in light of the specification disclosure, it is generally considered improper to read limitations contained in the specification into the claims. See In re Prater, 415 F.2d 1393, 162 USPQ 541 (CCPA 1969) and In re Winkhaus, 527 F.2d 637, 188 USPQ 129 (CCPA 1975), which discuss the premise that one cannot rely on the specification to impart limitations to the claim that are not recited in the claim.
Claim Rejections - 35 USC § 112 (a)
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 10 and 11 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The specification does not reasonably enable one of skill in the art to make and use the full scope of: a method for the treatment or prophylaxis of a central nervous system disorder, comprising administering to a patient in need thereof a compound according to claim 1, in free or pharmaceutically acceptable salt form, or a pharmaceutical composition thereof.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to use the full scope of the claimed invention without undue experimentation.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)”. The “use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed most recently in Liebel-Flarsheim Co. v. Medrad, Inc. 481 F.3d 1371, 82 USPQ2d 1113; Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008).
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’.” The court (In re Wands, 8 USPQ2d 1400 (1988)) established the following factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. § 112, first paragraph:
The nature of the invention
The breadth of the claims
The state of the prior art
The level of one of ordinary skill
The level of predictability in the art
The existence of working examples
The amount of direction provided by the inventor
the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The Wands factors have been considered with regard to the instant claims, with the most relevant factors discussed below.
Nature of Invention/Breadth of the Claims
The invention is drawn to a method for the treatment or prophylaxis of a central nervous system disorder, comprising administering to a patient in need thereof a compound according to claim 1, in free or pharmaceutically acceptable salt form, or a pharmaceutical composition thereof, wherein, as discussed above in claim interpretation, central nervous system disorder encompasses obesity, anxiety (including general anxiety, social anxiety, and panic disorders), depression (for example refractory depression and MDD), psychosis (including psychosis associated with dementia, such as hallucinations in advanced Parkinson's disease or paranoid delusions), schizophrenia, sleep disorders (particularly sleep disorders associated with schizophrenia and other psychiatric and neurological diseases), sexual disorders, migraine, pain and conditions associated with pain, including cephalic pain, idiopathic pain, chronic pain (such as moderate to moderately severe chronic pain, for example in patients requiring 24 hour extend treatment for other ailments), neuropathic pain, dental pain, fibromyalgia, chronic fatigue, agoraphobia, social phobias, agitation in dementia (e.g., agitation in Alzheimer's disease), agitation in autism and related autistic disorders, gastrointestinal disorders such as dysfunction of the gastrointestinal tract motility, and dementia, for example dementia of Alzheimer's disease or of Parkinson's disease; mood disorders; drug dependencies, for example, opioid dependency and/or alcohol dependency, and withdrawal from ding or alcohol dependency (e.g., opioid dependency); opioid overdose; co-morbidities associated with drug dependencies, such as depression, anxiety and psychosis; binge eating disorder; and obsessive- compulsive disorder (OCD), obsessive-compulsive personality disorder (OCPD)and related disorders; or opioid use disorder (OUD), or any combination thereof.
The disease genera of claims 10 and 11 are broad. For example, the claims recitation of “central nervous system disorder” encompasses a number of mechanistically divergent conditions may stem from multiple genetic and environmental factors.
central nervous system disorders include disorders of cognition. Sahakian (B. Sahakian et al., Philosophical Transactions B (2015) (“Sahakian”)) teaches that cognitive manifestations of neuropsychiatric disorders include disturbances in the regulation of attention (attentional biases), learning (aberrant learning), and in top– down regulation by the prefrontal cortex. [page 2, col. 1]. Furthermore, impairments of memory and executive function have been found in many neuropsychiatric disorders. [page 2, col. 1]. Many neuropsychiatric disorders have a neurodevelopmental origin and an onset or prodromal stage in childhood. [page 2, col. 1]. For example, Liberman (J. Liberman et al., The New England Journal of Medicine, 270-280 (2018)) teaches that psychoses can be categorized into three broad groups: idiopathic psychoses, psychoses due to medical conditions, and toxic psychoses. [page 270]1. Lieberman further teaches that as a consequence of their pathology, many disorders that have different causes and pathophysiological characteristics have altered neurotransmission in the dopamine and glutamate pathways of the hippocampus, midbrain, corpus striatum, and prefrontal cortex (Fig. 2), which leads to the emergence of psychotic symptoms. In another example, Grassetto (G. Grassetto et al., Nuclear Medicine Communications, 1085-1092 (2015)) teaches that Dementia is not a single nosological entity and many types of dementia exist and may be classified as follows: (a) reversible dementia, if resulting from another disease (generally infective, metabolic, or psychiatric conditions, tumoral lesions, normal pressure hydrocephalus); (b) vascular dementia; and (c) neurodegenerative primary dementia. [page 1085, col. 2].
State of the Art/Predictability
The art respecting treatment of the claimed conditions is unpredictable as evidenced by art as the relevant filing date. For example, Lee teaches that: there are four primary reasons why it is difficult to develop therapeutic agents against central nervous system disorders:
(1) CNS disorders have a complex etiology (heterogeneity; gene to environment),
(2) limitations of understanding pathophysiology in neuropsychiatric disorders,
(3) lack of appropriate biomarkers and/or molecular targets, and
(4) lack of appropriate animal models
H. Lee et al., Schizophrenia Research and Treatment (2016) (“Lee”) (see page 2, col. 1). Lee further teaches that: “[s]ince the etiological complexity restricts our understanding of pathophysiology of CNS disorders, it is difficult to identify and/or characterize appropriate biomarkers and/or molecular targets. As a result, it is difficult to evaluate the mechanism(s) of action of therapeutic agents”. Lee at page 2, col. 1.
In another example, Gibbs (R. Gibbs et al., Cell Stem Forum, 21-24 (2018)2) teaches that “The genetic complexity, clinical variability, and inaccessibility of affected tissue in neurodegenerative and neuropsychiatric disorders have largely prevented the development of effective disease-modifying therapeutics”. Gibbs further teaches that “CNS disorders result from a complex interplay between genetics and environment, and likely represent a broad categorization of many different molecular pathologies leading to uniform clinical presentations” [Gibbs at page 21, col. 2. At page 2, col. 3]. Gibbs further lists a number of significant challenges in developing therapeutics to treat neuropsychiatric disorders, for example, “the biological pathways driving key pathogenic processes remain largely unknown, making it difficult to identify discrete drug targets that modify disease progression”. In another example, Ritchie (C. Ritchie et al., 7 Alzheimer’s Research & Therapy, 1-11 (2015)) teaches that Despite decades of research, a cure or effective preventative treatment for dementia remains elusive. (see Abstract). Ritchie provides and in-depth discussion of challenges regarding treatment of dementia, including difficulty in diagnosis and problems with translating animal models to humans. Ritchie concludes that dementia 'cure' remains elusive and that problems with trial design, endpoint definitions and analysis may be contributory. Ritchie at page 9, col. 1. In another example, Voineskos teaches (Voineskos, D., et al. (2020), Neuropsychiatric Disease and Treatment, 16, 221–234, “Voineskos” cited in the PTO-892), challenges associated with mental illness treatment-resistant depression. [Title]. Voineskos teaches that these challenges include difficulties inherent in assessing the illness, a consensus model for treatment-resistant depression has not yet been established, and more studies are necessary to understand the appropriate treatment pathways. [Abstract]. Voineskos teaches that “there are several challenges which accompany the treatment of TRD, not the least of which is the relatively large proportion of patients with MDD who may be classified as having TRD. While several approaches, both traditional and novel, have been developed as described above, further work is necessary to understand the TRD as an illness to adequately treat TRD and notably, to ensure sustained response or continued remission. Several guidelines outlining the treatment of MDD may help to direct practitioners in a logical, step-wise approach (CANMAT, APA, NICE), however, specific guidelines for TRD have not been widely accepted to our knowledge.” [page 229, col. 1, 2nd para.]. In summary, the art of record teaches that treatment of central nervous system disorders is unpredictable due to the range of underlying causes, complex etiologies, and different disease mechanisms.
Guidance in the Art and Specification
The art of record does not disclose the claimed compounds reported to have the claimed activity. Further, neither the art of record nor the specification provides any reasonable correlation between the claimed compounds and treatment of the claimed diseases. Neither the art of record nor the specification provides any statistically relevant data documenting the activity of the claimed compounds in the treatment of the diseases claimed.
The exemplary embodiments of the specification in this case only sets forth binding assays and maximum inhibition assays on 5-HT2A for compounds A and B, other enantiomers of Formula I, and there is no binding assays or inhibition studies for claimed enantiomers, IA and IB. These assays do not provide a nexus between the claimed disorders and the claimed enantiomers. The specification does not describe the effectiveness of these enantiomers on 5-HT2A receptor, the specification does not provide any structure-activity relationships that correlates the structure of the claimed enantiomers with the treatment of particular CNS disorders, the specification does not draw connection between the claimed enantiomers and 5-HT2A activation, the provided examples does not teach skilled artisan how the claimed enantiomers would treat the claimed disorders.
Thus, the specification is very narrow compared to the claim breadth. There are no tests or studies directed to a method of treating the recited disorders, and no art recognized tests for predicting the efficacy of the claimed enantiomers.
The Quantity of Experimentation Needed Is Undue
Upon balancing the unpredictability in the art, the lack of correlation in the prior art or specification between the claimed compounds and the claimed treatment, and the lack of working examples, the quantity of experimentation is undue.
The claims are broadly directed to treatment of “central nervous system disorders” but neither the art of record nor the specification teach any working models, mechanisms of action, or other reasonable correlation linking the claimed compound to treatment of the full scope of disorders claimed. In this regard, as discussed above, the claimed breadth of diseases is large and the claimed diseases have different mechanisms, underlying causes and etiologies.
The art of record teaches significant unpredictability in the treatment of central nervous system disorders. For example, Gibbs lists a number of significant challenges in developing therapeutics to treat central nervous system disorders: “the biological pathways driving key pathogenic processes remain largely unknown, making it difficult to identify discrete drug targets that modify disease progression”. Gibbs at page 3, col. 3. In another example, Ritchie teaches that despite decades of research, a cure or effective preventative treatment for dementia remains elusive. Ritchie at Abstract.
The complex etiology and divergent mechanisms of claimed diseases and disorders and unpredictability taught by the art of record impose significant challenges in developing therapeutics to treat the claimed mental illnesses and CNS diseases, disorders and conditions. The specification does not supplement the art of record with the additional guidance needed to enable the full claim scope. Rather, the specification provides almost no guidance in this regard.
In sum, the primary factors underling this 112 rejection are lack of guidance in the specification and art of record; particularly a lack of a disclosed reasonable correlation between the claimed compound and treatment of the claimed diseases. Further, neither the art of record nor the specification discloses or propose a therapeutic mechanism by which the claimed compounds could be predicted to treat the full scope of claimed diseases. These primary factors are balanced with the large number of mechanistically diverse diseases claimed and the unpredictability in treating these disorders to establish a prima facie case that the experimentation required by one of skill in the art to practice the full claim scope is undue.
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 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.
§ 103 Rejection over Li
Claims 1-11 are rejected under 35 U.S.C. 103 as being unpatentable over P. Li et al. (WO 2020/132474A1, 06/25/2020, “Li” cited in the PTO-892).
Li teaches enantiomers of a substituted heterocycle fused gamma-carboline (Formula I):
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, in free, solid, pharmaceutically acceptable salt and/or substantially pure form, pharmaceutical compositions thereof, and methods of use in the treatment of diseases involving the 5-HT2A receptor, and pathways involving the dopamine D1 and D2 receptor signaling system, [Abstract [0008], [0010]]:
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Li teaches the enantiomers above include salt form and pharmaceutically acceptable salt form of the enantiomers, wherein the enantiomer is substantially pure diastereomeric form (i.e., substantially free from other diastereomers, including enantiomers having a diastereomeric excess of greater than 70%, preferably greater than 80%, more preferably greater than 90% and most preferably greater than 95%. Li teaches that an enantiomer from the above is in purified form (e.g., in at least 90% pure form, or at least 95% or at least 98% or at least 99%) [0011].
Li teaches that “is well known for enantiomers of pharmacologically active compounds to have different or opposite activities, such as one enantiomer being active and the other enantiomer being non-active. Li teaches that one of the enantiomers above has different relative activity at the 5-HT2A, and the pharmacological profile of one of the enantiomer is different than the other. Li teaches that this difference in activity profile provides new avenues for the treatment of disease based on this relatively enhanced pharmacologic activity at the D1 and 5-HT2A receptors. [0013], [0014].
Li teaches that the enantiomer is substantially pure, enantiomeric form, e.g., greater than 70% enantiomeric excess (“ee”), preferably greater than 80% ee, more preferably greater than 90% ee, most preferably greater than 95% ee. The separation and purification of the isomers from the diastereomeric mixtures is accomplished by standard techniques known in the art (e.g., column chromatography, preparative TLC, preparative HPLC, simulated moving bed and the like). [0062].
While Li teaches two cis enantiomers of Formula I, Li does not teach the claimed trans enantiomers, IA and IB.
However, the claimed IA and IB are obvious over Li and MPEP 2144.09:
As provided in MPEP 2144.09, a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963). Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious); Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007) (5(S) stereoisomer of ramipril obvious over prior art mixture of stereoisomers of ramipril). Homology and isomerism involve close structural similarity which must be considered with all other relevant facts in determining the issue of obviousness. In re Mills, 281 F.2d 218, 126 USPQ 513 (CCPA 1960); In re Wiechert, 370 F.2d 927, 152 USPQ 247 (CCPA 1967). Prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979). The presumption of obviousness based on a reference disclosing structurally similar compounds may be overcome where there is evidence showing there is no reasonable expectation of similar properties in structurally similar compounds. In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (appellant produced sufficient evidence to establish a substantial degree of unpredictability in the pertinent art area, and thereby rebutted the presumption that structurally similar compounds have similar properties); In re Schechter, 205 F.2d 185, 98 USPQ 144 (CCPA 1953). A prima facie case of obviousness based on structural similarity is rebuttable by proof that the claimed compounds possess unexpectedly advantageous or superior properties. In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) (affidavit evidence which showed that claimed triethylated compounds possessed anti-inflammatory activity whereas prior art trimethylated compounds did not was sufficient to overcome obviousness rejection based on the homologous relationship between the prior art and claimed compounds); In re Wiechert, 370 F.2d 927, 152 USPQ 247 (CCPA 1967) (a 7-fold improvement of activity over the prior art held sufficient to rebut prima facie obviousness based on close structural similarity). However, a claimed compound may be obvious because it was suggested by, or structurally similar to, a prior art compound even though a particular benefit of the claimed compound asserted by patentee is not expressly disclosed in the prior art. It is the differences, in fact, in their respective properties which are determinative of nonobviousness. If the prior art compound does in fact possess a particular benefit, even though the benefit is not recognized in the prior art, applicant’s recognition of the benefit is not in itself sufficient to distinguish the claimed compound from the prior art. In re Dillon, 919 F.2d 688, 693, 16 USPQ2d 1897, 1901 (Fed. Cir. 1990) (en banc).
In the instant case, and in view of MPEP 2144.09, Li’s compounds and the claimed compounds are enantiomers of compound of Formula I (please note that the MPEP stated that “Prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious “); the claimed compound and the prior art compound have very close structural similarities and very similar properties as the claimed compounds and prior art compounds have similar utilities on 5-HT2A; and Applicant does not provide evidences of unexpectedly advantageous or superior properties of the claimed enantiomers over the prior art enantiomers.
Moreover, Li examines two enantiomers of the four enantiomers at the highlighted diastereomeric position of Formula I above and reported that one of the enantiomers above is more active on the 5-HT2A than the other and has better pharmacological profile, which indicates the essential role of this diastereomeric position of the compound of Formula I; Li teaches that this difference in activity profile provides new avenues for the treatment of disease based on this relatively enhanced pharmacologic activity at the D1 and 5-HT2A receptors; and Li teaches that “is well known for enantiomers of pharmacologically active compounds to have different or opposite activities”. Furthermore, Li explicitly teaches that compound of Formula I encompasses diastereomeric mixtures thereof. [0062]. Thus, one of ordinary skill would have been motivated with reasonable expectation of success to prepare and evaluate the other two enantiomers against 5-HT2A. Therefore, claims 1-3 are obvious over Li.
With regard to claims 4, 5 and 6, one of ordinary skill in the art would have to prepare excess of one enantiomer, for example IA over the other e.g., at least 55%-95 mol% because Li provides motivation to prepare substantially pure enantiomers of Formula I as discussed above, and because Li explicitly teaches that enantiomeric forms of Formula I are substantially pure, enantiomeric form, e.g., greater than 70% enantiomeric excess (“ee”), preferably greater than 80% ee, more preferably greater than 90% ee, most preferably greater than 95% ee. [0062].
With regard to claims 7 and 8, Li teaches that the enantiomers of Formula I include salt form and pharmaceutically acceptable salt form of the enantiomers, wherein the enantiomer is substantially pure diastereomeric form (i.e., substantially free from other diastereomers, including enantiomers having a diastereomeric excess of greater than 70%, preferably greater than 80%, more preferably greater than 90% and most preferably greater than 95%. Li teaches that an enantiomer from the above is in purified form (e.g., in at least 90% pure form, or at least 95% or at least 98% or at least 99%) [0011].
With regard to claim 9, Li teaches a pharmaceutical composition comprising an enantiomer of Formula I in admixture with a pharmaceutically acceptable diluent or carrier. [0109].
With regard to claims 10 and 11, Li teaches a method for the treatment or prophylaxis of a central nervous system disorder by administering an enantiomer of Formula I, [0135], wherein the central nervous system disorder is a disorder selected from a group consisting of obesity, anxiety, depression, schizophrenia, sleep disorders, dementia, etc. [0151].
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Double Patenting Rejection over US Patent No. 12440489 B2
Claims 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of US Patent No. 12440489 B2 (US Application No. 18/502,460) in view of Li et al. (WO2020/132474A1, 06/25/2020, “Li” cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1-11 recite “a compound of Formula I having trans-stereochemistry across 6b and 10a, wherein the compound of Formula I is a mixture of IA and IB:
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wherein the compound of is a racemic mixture of IA and IB, wherein the compound of Formula I has a molar excess of IA of at least 55-95mol%, wherein the compound of Formula I has a molar excess of IB of at least 55-95mol%, wherein the compound of Formula I is substantially free of other compounds, wherein the compound of Formula I is substantially pure form of at least 90-99% pure form, and wherein the compounds is in the form of a pharmaceutically acceptable salt. The claims also recite a pharmaceutical composition comprising the compound of Formula I in admixture with a pharmaceutically acceptable diluent or carrier, and method for the treatment or prophylaxis of a central nervous system disorder, comprising administering to a patient in need thereof the compound of Formula I.
US Patent No. 12440489 B2 recites a method of treatment of a central nervous system disorder by administering a compound of Formula I and a salt thereof:
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While US Patent No. 12440489 B2 recite cis enantiomer of Formula I, US Patent No. 12440489 B2 does not teach the claimed trans enantiomers, IA and IB. However, claims 1-11 are obvious over US Patent No. 12440489 B2 in view of Li.
Li teaches as discussed above and incorporated herein by reference, page 14-15.
The obviousness rationale is similar to the rationale in the 103 Rejection above, page 15-17.
Double Patenting Rejection over US Patent No. 11844757 B2
Claims 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-7 and 9-14 of US Patent No. 11844757 B2 in view of Li et al. (WO2020/132474A1, 06/25/2020, “Li” cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1-11 recite “a compound of Formula I having trans-stereochemistry across 6b and 10a, wherein the compound of Formula I is a mixture of IA and IB:
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wherein the compound of is a racemic mixture of IA and IB, wherein the compound of Formula I has a molar excess of IA of at least 55-95mol%, wherein the compound of Formula I has a molar excess of IB of at least 55-95mol%, wherein the compound of Formula I is substantially free of other compounds, wherein the compound of Formula I is substantially pure form of at least 90-99% pure form, and wherein the compounds is in the form of a pharmaceutically acceptable salt. The claims also recite a pharmaceutical composition comprising the compound of Formula I in admixture with a pharmaceutically acceptable diluent or carrier, and method for the treatment or prophylaxis of a central nervous system disorder, comprising administering to a patient in need thereof the compound of Formula I.
US Patent No. 11844757 B2 recites a method of treatment of a central nervous system disorder by administering a compound of Formula I and a salt thereof:
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While US Patent No. 11844757 B2 recite cis enantiomer of Formula I, US Patent No. 11844757 B2 does not teach the claimed trans enantiomers, IA and IB. However, claims 1-11 are obvious over US Patent No. 11844757 B2 in view of Li.
Li teaches as discussed above and incorporated herein by reference, page 14-15.
The obviousness rationale is similar to the rationale in the 103 Rejection above, page 15-17.
Double Patenting Rejection over US Patent No. 11376249 B2
Claims 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-7 and 15-19 of US Patent No. 11376249 B2 in view of Li et al. (WO2020/132474A1, 06/25/2020, “Li” cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1-11 recite “a compound of Formula I having trans-stereochemistry across 6b and 10a, wherein the compound of Formula I is a mixture of IA and IB:
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wherein the compound of is a racemic mixture of IA and IB, wherein the compound of Formula I has a molar excess of IA of at least 55-95mol%, wherein the compound of Formula I has a molar excess of IB of at least 55-95mol%, wherein the compound of Formula I is substantially free of other compounds, wherein the compound of Formula I is substantially pure form of at least 90-99% pure form, and wherein the compounds is in the form of a pharmaceutically acceptable salt. The claims also recite a pharmaceutical composition comprising the compound of Formula I in admixture with a pharmaceutically acceptable diluent or carrier, and method for the treatment or prophylaxis of a central nervous system disorder, comprising administering to a patient in need thereof the compound of Formula I.
US Patent No. 11376249 B2 recites a method of treatment of a central nervous system disorder by administering a compound of Formula I in a free or salt form:
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While US Patent No. 11376249 B2 recite cis enantiomer of Formula I, US Patent No. 11376249 B2 does not teach the claimed trans enantiomers, IA and IB. However, claims 1-11 are obvious over US Patent No. 11376249 B2 in view of Li.
Li teaches as discussed above and incorporated herein by reference, page 14-15.
The obviousness rationale is similar to the rationale in the 103 Rejection above, page 15-17.
Double Patenting Rejection over US Patent No. 10799500 B2
Claims 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 3-17 of US Patent No. 10799500 B2 in view of Li et al. (WO2020/132474A1, 06/25/2020, “Li” cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1-11 recite “a compound of Formula I having trans-stereochemistry across 6b and 10a, wherein the compound of Formula I is a mixture of IA and IB:
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wherein the compound of is a racemic mixture of IA and IB, wherein the compound of Formula I has a molar excess of IA of at least 55-95mol%, wherein the compound of Formula I has a molar excess of IB of at least 55-95mol%, wherein the compound of Formula I is substantially free of other compounds, wherein the compound of Formula I is substantially pure form of at least 90-99% pure form, and wherein the compounds is in the form of a pharmaceutically acceptable salt. The claims also recite a pharmaceutical composition comprising the compound of Formula I in admixture with a pharmaceutically acceptable diluent or carrier, and method for the treatment or prophylaxis of a central nervous system disorder, comprising administering to a patient in need thereof the compound of Formula I.
US Patent No. 10799500 B2 recites a compound of Formula I in free form, salt form, or pharmaceutically acceptable salt form:
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With regarding to claim 10 and 11 method of treating central nervous system disorder, US Patent No. 10799500 B2 recites the utility of compound of Formula I at col. 16, ln. 17 to col. 17 ln. 15 of the specification. Consistent with Sun Pharmaceutical Industries v. Eli Lilly and Col, 611 F. 3d 1381, 1387 (CAFC 2010), it is permissible to use a compound claim to reject a method of use claim where that method of use is disclosed in the specification of the application claiming the compound. According to the Sun Pharma. Court, “[i]t would shock one' s sense of justice if an inventor could receive a patent upon a composition of matter, setting out at length in the specification the useful purposes of such composition, . . .and then prevent the public from making any beneficial use of such product by securing patents upon each of the uses to which it may be adapted. . .”.
While US Patent No. 10799500 B2 recite cis enantiomer of Formula I, US Patent No. 10799500 B2 does not teach the claimed trans enantiomers, IA and IB. However, claims 1-11 are obvious over US Patent No. 10799500 B2 in view of Li.
Li teaches as discussed above and incorporated herein by reference, page 14-15.
The obviousness rationale is similar to the rationale in the 103 Rejection above, page 15-17.
Double Patenting Rejection over US Patent No. 10245260 B2
Claims 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-9 of US Patent No. 10245260 B2 in view of Li et al. (WO2020/132474A1, 06/25/2020, “Li” cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1-11 recite “a compound of Formula I having trans-stereochemistry across 6b and 10a, wherein the compound of Formula I is a mixture of IA and IB:
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wherein the compound of is a racemic mixture of IA and IB, wherein the compound of Formula I has a molar excess of IA of at least 55-95mol%, wherein the compound of Formula I has a molar excess of IB of at least 55-95mol%, wherein the compound of Formula I is substantially free of other compounds, wherein the compound of Formula I is substantially pure form of at least 90-99% pure form, and wherein the compounds is in the form of a pharmaceutically acceptable salt. The claims also recite a pharmaceutical composition comprising the compound of Formula I in admixture with a pharmaceutically acceptable diluent or carrier, and method for the treatment or prophylaxis of a central nervous system disorder, comprising administering to a patient in need thereof the compound of Formula I.
US Patent No. 10245260 B2 recites a method of treatment of a central nervous system disorder by administering a compound of Formula I in a free or salt form:
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While US Patent No. 10245260 B2 recite cis enantiomer of Formula I, US Patent No. 10245260 B2 does not teach the claimed trans enantiomers, IA and IB. However, claims 1-11 are obvious over US Patent No. 10245260 B2 in view of Li.
Li teaches as discussed above and incorporated herein by reference, page 14-15.
The obviousness rationale is similar to the rationale in the 103 Rejection above, page 15-17.
Double Patenting Rejection over US Patent No. 12023331 B2
Claims 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of US Patent No. 12023331 B2 in view of Li et al. (WO2020/132474A1, 06/25/2020, “Li” cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1-11 recite “a compound of Formula I having trans-stereochemistry across 6b and 10a, wherein the compound of Formula I is a mixture of IA and IB:
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wherein the compound of is a racemic mixture of IA and IB, wherein the compound of Formula I has a molar excess of IA of at least 55-95mol%, wherein the compound of Formula I has a molar excess of IB of at least 55-95mol%, wherein the compound of Formula I is substantially free of other compounds, wherein the compound of Formula I is substantially pure form of at least 90-99% pure form, and wherein the compounds is in the form of a pharmaceutically acceptable salt. The claims also recite a pharmaceutical composition comprising the compound of Formula I in admixture with a pharmaceutically acceptable diluent or carrier, and method for the treatment or prophylaxis of a central nervous system disorder, comprising administering to a patient in need thereof the compound of Formula I.
US Patent No. 12023331 B2 recites a method of treatment of acute depression or acute anxiety comprising administering to a patient in need thereof, a therapeutically effective amount of a Compound of Formula I:
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While US Patent No. 12023331 B2 recite cis enantiomer of Formula I, US Patent No. 12023331 B2 does not teach the claimed trans enantiomers, IA and IB. However, claims 1-11 are obvious over US Patent No. 12023331 B2 in view of Li.
Li teaches as discussed above and incorporated herein by reference, page 14-15.
The obviousness rationale is similar to the rationale in the 103 Rejection above, page 15-17.
Double Patenting Rejection over US Patent No. 12195463B2
Claims 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of US Patent No. 12195463B2. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1-11 recite “a compound of Formula I having trans-stereochemistry across 6b and 10a, wherein the compound of Formula I is a mixture of IA and IB:
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wherein the compound of is a racemic mixture of IA and IB, wherein the compound of Formula I has a molar excess of IA of at least 55-95mol%, wherein the compound of Formula I has a molar excess of IB of at least 55-95mol%, wherein the compound of Formula I is substantially free of other compounds, wherein the compound of Formula I is substantially pure form of at least 90-99% pure form, and wherein the compounds is in the form of a pharmaceutically acceptable salt. The claims also recite a pharmaceutical composition comprising the compound of Formula I in admixture with a pharmaceutically acceptable diluent or carrier, and method for the treatment or prophylaxis of a central nervous system disorder, comprising administering to a patient in need thereof the compound of Formula I.
US Patent No. 12195463B2 recites a compound of Formula I:
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in free or pharmaceutically acceptable salt form, wherein the compound is in isolated and purified form of at least 90% purity, wherein the compound has a diastereomeric excess greater than 90%, wherein the compound is in isolated or purified form of at least 98% purity, wherein the compound has an enantiomeric excess greater than 90%. The claims recite a pharmaceutical composition comprising Formula I, in free or pharmaceutically acceptable salt form, in admixture with a pharmaceutically acceptable diluent or carrier, and a method for the treatment or prophylaxis of a central nervous system disorder, comprising administering to a patient in need thereof Formula I, in free or pharmaceutically acceptable salt form, wherein said disorder is selected from the group consisting of general anxiety, social anxiety, panic disorders, refractory depression, major depressive disorder, psychosis associated with dementia, etc., wherein said disorder is a disorder involving the serotonin 5-HT2A, serotonin reuptake transporter (SERT), dopamine D1 and/or D2 pathways.
The claimed IA and IB are obvious over US Patent No. 12195463B2 and MPEP 2144.09:
As provided in MPEP 2144.09, a prima facie case of obviousness may be made when chemical compounds have very close structural similarities and similar utilities. "An obviousness rejection based on similarity in chemical structure and function entails the motivation of one skilled in the art to make a claimed compound, in the expectation that compounds similar in structure will have similar properties." In re Payne, 606 F.2d 303, 313, 203 USPQ 245, 254 (CCPA 1979). See In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963). Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious); Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007) (5(S) stereoisomer of ramipril obvious over prior art mixture of stereoisomers of ramipril). Homology and isomerism involve close structural similarity which must be considered with all other relevant facts in determining the issue of obviousness. In re Mills, 281 F.2d 218, 126 USPQ 513 (CCPA 1960); In re Wiechert, 370 F.2d 927, 152 USPQ 247 (CCPA 1967). Prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious. In re Payne, 606 F.2d 303, 203 USPQ 245 (CCPA 1979). The presumption of obviousness based on a reference disclosing structurally similar compounds may be overcome where there is evidence showing there is no reasonable expectation of similar properties in structurally similar compounds. In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (appellant produced sufficient evidence to establish a substantial degree of unpredictability in the pertinent art area, and thereby rebutted the presumption that structurally similar compounds have similar properties); In re Schechter, 205 F.2d 185, 98 USPQ 144 (CCPA 1953). A prima facie case of obviousness based on structural similarity is rebuttable by proof that the claimed compounds possess unexpectedly advantageous or superior properties. In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963) (affidavit evidence which showed that claimed triethylated compounds possessed anti-inflammatory activity whereas prior art trimethylated compounds did not was sufficient to overcome obviousness rejection based on the homologous relationship between the prior art and claimed compounds); In re Wiechert, 370 F.2d 927, 152 USPQ 247 (CCPA 1967) (a 7-fold improvement of activity over the prior art held sufficient to rebut prima facie obviousness based on close structural similarity). However, a claimed compound may be obvious because it was suggested by, or structurally similar to, a prior art compound even though a particular benefit of the claimed compound asserted by patentee is not expressly disclosed in the prior art. It is the differences, in fact, in their respective properties which are determinative of nonobviousness. If the prior art compound does in fact possess a particular benefit, even though the benefit is not recognized in the prior art, applicant’s recognition of the benefit is not in itself sufficient to distinguish the claimed compound from the prior art. In re Dillon, 919 F.2d 688, 693, 16 USPQ2d 1897, 1901 (Fed. Cir. 1990) (en banc). In the instant case, and in view of MPEP 2144.09, the claimed compound and prior arts compounds are enantiomers of compound of Formula I. Please note that the MPEP stated that “Prior art structures do not have to be true homologs or isomers to render structurally similar compounds prima facie obvious “. The claimed compound and the prior art compound have very close structural similarities and very similar properties as the claimed compounds and prior art compounds have similar utilities on 5-HT2A, and Applicant does not provide evidences of unexpectedly advantageous or superior properties of the claimed enantiomers over the prior art enantiomers. Moreover, claims 2, 10, 11 and 14 recite that the compound is at least 90% pure, isolated and purified to at least 98%, has a diastereomeric excess greater than 90%, and has an enantiomeric excess greater than 90%. By preparing one of the enantiomer of Formula I as a medicament for treating central nervous system disorder, US Patent No. 12195463B2 would motivates one of ordinary skill in the art to prepare and evaluate the other enantiomers against 5-HT2A for treating central nervous system disorder.
Double Patenting Rejection over US Patent No. 12297200B2
Claims 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of US Patent No. 12297200B2 in view of Li et al. (WO2020/132474A1, 06/25/2020, “Li” cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1-11 recite “a compound of Formula I having trans-stereochemistry across 6b and 10a, wherein the compound of Formula I is a mixture of IA and IB:
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wherein the compound of is a racemic mixture of IA and IB, wherein the compound of Formula I has a molar excess of IA of at least 55-95mol%, wherein the compound of Formula I has a molar excess of IB of at least 55-95mol%, wherein the compound of Formula I is substantially free of other compounds, wherein the compound of Formula I is substantially pure form of at least 90-99% pure form, and wherein the compounds is in the form of a pharmaceutically acceptable salt. The claims also recite a pharmaceutical composition comprising the compound of Formula I in admixture with a pharmaceutically acceptable diluent or carrier, and method for the treatment or prophylaxis of a central nervous system disorder, comprising administering to a patient in need thereof the compound of Formula I.
US Patent No. 12297200B2 recites a method of preparing a compound of Formula 1J in free or salt form, and a pharmaceutical composition of Formula 1J in at least 97% purity:
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With regarding to claim 10 and 11 method of treating central nervous system disorder, US Patent No. 12297200 B2 recites that the compound is useful for the treatment or prophylaxis of central nervous system disorders, [col. 2, ln. 61-63]. Consistent with Sun Pharmaceutical Industries v. Eli Lilly and Col, 611 F. 3d 1381, 1387 (CAFC 2010), it is permissible to use a compound claim to reject a method of use claim where that method of use is disclosed in the specification of the application claiming the compound. According to the Sun Pharma. Court, “[i]t would shock one' s sense of justice if an inventor could receive a patent upon a composition of matter, setting out at length in the specification the useful purposes of such composition, . . .and then prevent the public from making any beneficial use of such product by securing patents upon each of the uses to which it may be adapted. . .”.
While US Patent No. 12297200B2 recite cis enantiomer of Formula I, US Patent No. 12297200B2 does not teach the claimed trans enantiomers, IA and IB. However, claims 1-11 are obvious over US Patent No. 12297200B2 in view of Li.
Li teaches as discussed above and incorporated herein by reference, page 14-15.
The obviousness rationale is similar to the rationale in the 103 Rejection above, page 15-17.
Double Patenting Rejection over co-pending Application No. 18/670,391
Claims 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7, 9-11 and 22-25 of co-pending Application No. 18/670,391 (US20240307386A1) in view of Li et al. (WO2020/132474A1, 06/25/2020, “Li” cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1-11 recite “a compound of Formula I having trans-stereochemistry across 6b and 10a, wherein the compound of Formula I is a mixture of IA and IB:
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wherein the compound of is a racemic mixture of IA and IB, wherein the compound of Formula I has a molar excess of IA of at least 55-95mol%, wherein the compound of Formula I has a molar excess of IB of at least 55-95mol%, wherein the compound of Formula I is substantially free of other compounds, wherein the compound of Formula I is substantially pure form of at least 90-99% pure form, and wherein the compounds is in the form of a pharmaceutically acceptable salt. The claims also recite a pharmaceutical composition comprising the compound of Formula I in admixture with a pharmaceutically acceptable diluent or carrier, and method for the treatment or prophylaxis of a central nervous system disorder, comprising administering to a patient in need thereof the compound of Formula I.
co-pending Application No. 18/670,391 recites a method of treatment of a central nervous system disorder by administering a compound of Formula I in free or salt form:
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While co-pending Application No. 18/670,391 recite cis enantiomer of Formula I, co-pending Application No. 18/670,391 does not teach the claimed trans enantiomers, IA and IB. However, claims 1-11 are obvious over co-pending Application No. 18/670,391 in view of Li.
Li teaches as discussed above and incorporated herein by reference, page 14-15.
The obviousness rationale is similar to the rationale in the 103 Rejection above, page 15-17.
Double Patenting Rejection over co-pending Application No. 17/832,282
Claims 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 5-6 and 9-18 of co-pending Application No. 17/832,282 (US20220296591A1) in view of Li et al. (WO2020/132474A1, 06/25/2020, “Li” cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1-11 recite “a compound of Formula I having trans-stereochemistry across 6b and 10a, wherein the compound of Formula I is a mixture of IA and IB:
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wherein the compound of is a racemic mixture of IA and IB, wherein the compound of Formula I has a molar excess of IA of at least 55-95mol%, wherein the compound of Formula I has a molar excess of IB of at least 55-95mol%, wherein the compound of Formula I is substantially free of other compounds, wherein the compound of Formula I is substantially pure form of at least 90-99% pure form, and wherein the compounds is in the form of a pharmaceutically acceptable salt. The claims also recite a pharmaceutical composition comprising the compound of Formula I in admixture with a pharmaceutically acceptable diluent or carrier, and method for the treatment or prophylaxis of a central nervous system disorder, comprising administering to a patient in need thereof the compound of Formula I.
co-pending Application No. 17/832,282 recites a method of treatment of a central nervous system disorder by administering a compound of Formula I in free or salt form:
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While co-pending Application No. 17/832,282 recite cis enantiomer of Formula I, co-pending Application No. 17/832,282 does not teach the claimed trans enantiomers, IA and IB. However, claims 1-11 are obvious over co-pending Application No. 17/832,282 in view of Li.
Li teaches as discussed above and incorporated herein by reference, page 14-15.
The obviousness rationale is similar to the rationale in the 103 Rejection above, page 15-17.
Double Patenting Rejection over co-pending Application No. 19/176,720
Claims 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 18, 22 and 24-25 of co-pending Application No. 19/176,720 (US20260098040A1) in view of Li et al. (WO2020/132474A1, 06/25/2020, “Li” cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1-11 recite “a compound of Formula I having trans-stereochemistry across 6b and 10a, wherein the compound of Formula I is a mixture of IA and IB:
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wherein the compound of is a racemic mixture of IA and IB, wherein the compound of Formula I has a molar excess of IA of at least 55-95mol%, wherein the compound of Formula I has a molar excess of IB of at least 55-95mol%, wherein the compound of Formula I is substantially free of other compounds, wherein the compound of Formula I is substantially pure form of at least 90-99% pure form, and wherein the compounds is in the form of a pharmaceutically acceptable salt. The claims also recite a pharmaceutical composition comprising the compound of Formula I in admixture with a pharmaceutically acceptable diluent or carrier, and method for the treatment or prophylaxis of a central nervous system disorder, comprising administering to a patient in need thereof the compound of Formula I.
Co-pending Application No. 19/176,720 recites a method of preparing a compound of Formula I in free or salt form, and a pharmaceutical composition comprising a compound of Formula 1J:
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With regarding to claim 10 and 11 method of treating central nervous system disorder, Co-pending Application No. 19/176,720 recites that the compound is useful for the treatment or prophylaxis of central nervous system disorders, [0006]. Consistent with Sun Pharmaceutical Industries v. Eli Lilly and Col, 611 F. 3d 1381, 1387 (CAFC 2010), it is permissible to use a compound claim to reject a method of use claim where that method of use is disclosed in the specification of the application claiming the compound. According to the Sun Pharma. Court, “[i]t would shock one' s sense of justice if an inventor could receive a patent upon a composition of matter, setting out at length in the specification the useful purposes of such composition, . . .and then prevent the public from making any beneficial use of such product by securing patents upon each of the uses to which it may be adapted. . .”.
While co-pending Application No. 19/176,720 recite cis enantiomer of Formula I, co-pending Application No. 19/176,720 does not teach the claimed trans enantiomers, IA and IB. However, claims 1-11 are obvious over co-pending Application No. 19/176,720 in view of Li.
Li teaches as discussed above and incorporated herein by reference, page 14-15.
The obviousness rationale is similar to the rationale in the 103 Rejection above, page 15-17.
Double Patenting Rejection over co-pending Application No. 19/181,262
Claims 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 5, 7-10, 15-19 and 22 of co-pending Application No. 19/181,262 (reference application) in view of Li et al. (WO2020/132474A1, 06/25/2020, “Li” cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1-11 recite “a compound of Formula I having trans-stereochemistry across 6b and 10a, wherein the compound of Formula I is a mixture of IA and IB:
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wherein the compound of is a racemic mixture of IA and IB, wherein the compound of Formula I has a molar excess of IA of at least 55-95mol%, wherein the compound of Formula I has a molar excess of IB of at least 55-95mol%, wherein the compound of Formula I is substantially free of other compounds, wherein the compound of Formula I is substantially pure form of at least 90-99% pure form, and wherein the compounds is in the form of a pharmaceutically acceptable salt. The claims also recite a pharmaceutical composition comprising the compound of Formula I in admixture with a pharmaceutically acceptable diluent or carrier, and method for the treatment or prophylaxis of a central nervous system disorder, comprising administering to a patient in need thereof the compound of Formula I.
co-pending Application No. 19/181,262 recites a method of treatment or prevention of opiate addiction in a patient suffers from anxiety, depression, psychosis, dementia, etc., by administering a compound of Formula I in a free or salt form:
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While co-pending Application No. 19/181,262 recite cis enantiomer of Formula I, co-pending Application No. 19/181,262 does not teach the claimed trans enantiomers, IA and IB. However, claims 1-11 are obvious over co-pending Application No. 19/181,262 in view of Li.
Li teaches as discussed above and incorporated herein by reference, page 14-15.
The obviousness rationale is similar to the rationale in the 103 Rejection above, page 15-17.
Double Patenting Rejection over co-pending Application No. 19/239,540
Claims 1-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 17-19 of co-pending Application No. 19/239,540 (reference application) in view of Li et al. (WO2020/132474A1, 06/25/2020, “Li” cited in the PTO-892). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Instant claims 1-11 recite “a compound of Formula I having trans-stereochemistry across 6b and 10a, wherein the compound of Formula I is a mixture of IA and IB:
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wherein the compound of is a racemic mixture of IA and IB, wherein the compound of Formula I has a molar excess of IA of at least 55-95mol%, wherein the compound of Formula I has a molar excess of IB of at least 55-95mol%, wherein the compound of Formula I is substantially free of other compounds, wherein the compound of Formula I is substantially pure form of at least 90-99% pure form, and wherein the compounds is in the form of a pharmaceutically acceptable salt. The claims also recite a pharmaceutical composition comprising the compound of Formula I in admixture with a pharmaceutically acceptable diluent or carrier, and method for the treatment or prophylaxis of a central nervous system disorder, comprising administering to a patient in need thereof the compound of Formula I.
co-pending Application No. 19/239,540 recites a method of treatment of neuropathic pain (central nervous system disorder, see claim interpterion above) by administering a compound of Formula I in a free or salt form:
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While co-pending Application No. 19/239,540 recite cis enantiomer of Formula I, co-pending Application No. 19/239,540 does not teach the claimed trans enantiomers, IA and IB. However, claims 1-11 are obvious over co-pending Application No. 19/239,540 in view of Li.
Li teaches as discussed above and incorporated herein by reference, page 14-15.
The obviousness rationale is similar to the rationale in the 103 Rejection above, page 15-17.
Conclusion
Claims 1-11 are rejected. No claims are allowed.
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/M.M.A./Examiner, Art Unit 1622
/JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
1 Later publications showing factual evidence can be cited include situations where the facts shown in the reference are evidence "that, as of an application’s filing date, undue experimentation would have been required. MPEP 2124.
2 Later publications showing factual evidence can be cited include situations where the facts shown in the reference are evidence "that, as of an application’s filing date, undue experimentation would have been required. MPEP 2124.
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