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 16-35 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 U.S. National Stage Entry of PCT/EP22/57015, filed 03/17/2022. PCT/EP22/57015 claims priority of foreign application EP21382221.6, filed 03/18/2021. Therefore, the effective filing date is 03/18/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09/21/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 16-26 and 30-35 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 written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The courts have stated that, “To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated that, “A written description of an invention involving a chemical genus, like a description of a chemical species, ‘requires a precise definition, such as by structure, formula, [or] chemical name,’ of the claimed subject matter sufficient to distinguish it from other materials.” Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) (“In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus …”) Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed genus is sufficient. See MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
In the instant case, claims 16, 26, and 35 are drawn to compounds/compositions of Formula (I) and/or a “prodrug thereof”.
The compounds of Formula (I) are structurally defined. However, the genus of “a prodrug” of Formula (I) is not fully structurally defined. It is unclear what is encompassed by the term “prodrug”. The specification provides a definition for a “prodrug” as follows (see pg. 15): The term "prodrug" is used in its broadest sense and encompasses those derivatives that are converted in vivo to the compounds of the invention.
Prodrugs are derivatives or precursors of therapeutically active molecules which undergo bioconversion into their active form inside the body. See, for example, Walther et al. (“Prodrugs in Medicinal Chemistry and Enzyme Prodrug Therapies.” Advanced Drug Delivery Reviews, vol. 118, Sept. 2017, pp. 65–77), which discusses prodrugs in medicinal chemistry and enzyme prodrug therapies. Prodrugs are typically employed when, for example, the parent drug compound has poor aqueous solubility, poor absorption from the gastro-intestinal tract into the blood, poor rates of cell entry, or various other reasons (see Table 1 of Walther). Design strategy for a prodrug depends on the structural features of the parent drug molecule and availability of the appropriate chemical functionalities that can be used to mask pharmacodynamic activity of the drug through an attachment of a modifying group. Typically, an enzymatic process is relied upon for drug release.
In particular, Walther notes that esters are commonly used as prodrugs due to the ubiquity of esterases in the body and the abundance of hydroxyl and carboxylic acid functionalities in drug compounds (see pg. 67, “Esterases: a “universal tool for drug recovery”).
However, a person having ordinary skill would not readily envisage a prodrug of Formula (I) having an ester, because there is no hydroxyl or carboxylic acid functionality in the compounds. Walther discloses other common prodrugs for bioconversion, such as phosphate prodrugs, nitrophenyl prodrugs, glycoside prodrugs, and others. However, these various strategies are relied upon typically to release free hydroxyl or amino groups, which are not present in the compounds of Formula (I).
Applicant’s specification provides no examples of a “prodrug” of the compounds of Formula (I). Additionally, no disclosure is provided which would guide a person of ordinary skill toward a particular prodrug strategy or design for the compounds of Formula (I).
The compounds of Formula (I) and “prodrug thereof” are not described in the prior art. They appear to be a new set of compounds with an affinity for sigma receptors, and thus, information about their properties which would guide a person of ordinary skill toward a particular derivative or prodrug structure is also not disclosed in the prior art.
Methods of synthesizing compounds are, in general, known to the person of ordinary skill, however methods of making the myriad of compounds embraced by the instant claims is beyond the skill of the artisan, particularly when certain elements, such as “a prodrug”, are merely described partially. As such, the instant specification and instant claims do not provide sufficient description such that one could anticipate what additional elements may be present in the prodrugs of Formula (I).
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Dependent claims 17-25 and 30-34 do not resolve these issues, since these claims do not further limit or provide further structure of the “prodrug”. Accordingly, these claims are also rejected.
Claims 27-29 are objected to as being dependent upon a rejected claim.
The rejection would be overcome by amending the claims to remove the term “prodrug”.
Claims 30-34 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of binding to σ1 receptors comprising administering a compound of formula (I), does not reasonably provide enablement for the treatment of any clinical condition associated with a sigma receptor, including those listed in claim 34. 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 disease associated with a sigma receptor in a patient, comprising administering a compound of the formula (I). This is taught to include any clinical condition associated with a sigma receptor, including those specific conditions listed in claim 34.
Nature of the invention
The nature of the invention is performance of a method of treating a disease associated with a sigma receptor in a patient, comprising administering a compound of formula (I). The compounds of formula (I) are taught to bind to σ1 receptors.
State of the prior art
No single drug has been discovered that is effective in treating the myriad of sigma receptor related conditions in a patient, such as pain, including but not limited to neuropathic pain, inflammatory pain, chronic pain, a pain condition involving allodynia and/or hyperalgesia, and all CNS diseases and disorders, including but not limited to addiction to drugs and chemical substances, anxiety, attention- deficit-/hyperactivity disorder (ADHD), autism spectrum disorder, catalepsy, cognition disorder, learning, memory and attention deficit, depression, encephalitis, epilepsy, headache disorder, insomnia, locked-in-syndrome, meningitis, migraine, multiple sclerosis (MS), leukodystrophies, amyotrophic lateral sclerosis (ALS), myelopathy, narcolepsy, neurodegenerative disease, traumatic brain injury, Alzheimer disease, Gaucher's disease, Huntington disease, Parkinson disease, Tourette's syndrome, psychotic condition, bipolar disorder, schizophrenia and paranoia. See In re Hokum, 226 USPQ 353 (ComrPats 1985).
The compounds appear novel, so the prior art does not teach the treatment of any specific sigma receptor related conditions comprising administering compounds of formula (I).
Level of one of ordinary skill in the art
The artisans performing the inventor’s or joint inventor’s method of treating a sigma receptor related condition 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 sigma receptor related condition 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 sigma receptor related condition 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 conditions, such as pain, including but not limited to neuropathic pain, inflammatory pain, chronic pain, a pain condition involving allodynia and/or hyperalgesia, and all CNS diseases and disorders, including but not limited to addiction to drugs and chemical substances, anxiety, attention- deficit-/hyperactivity disorder (ADHD), autism spectrum disorder, catalepsy, cognition disorder, learning, memory and attention deficit, depression, encephalitis, epilepsy, headache disorder, insomnia, locked-in-syndrome, meningitis, migraine, multiple sclerosis (MS), leukodystrophies, amyotrophic lateral sclerosis (ALS), myelopathy, narcolepsy, neurodegenerative disease, traumatic brain injury, Alzheimer disease, Gaucher's disease, Huntington disease, Parkinson disease, Tourette's syndrome, psychotic condition, bipolar disorder, schizophrenia and paranoia.
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 examples for the binding of compounds of formula (I) to σ1 receptors. There is insufficient disclosure to reasonably conclude that the method of treating any sigma receptor related condition in a patient, comprising administering a compound of formula (I), as recited, would contribute to treatment 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 thousands 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 sigma receptor related diseases. Even in vitro and in vivo assays do not always correlate to efficacy in humans and are not generally predictive of clinical efficacy.
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 sigma receptor related condition 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 30 and 31 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.
The inventor or joint inventor should note that claims 30 and 31 are reach-through claims. 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 sigma receptor related diseases or conditions 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 25 and 26, provides nonlimiting examples of treatable sigma receptor related diseases or conditions as “pain, especially neuropathic pain, inflammatory pain, and chronic pain or other pain conditions involving allodynia and/or hyperalgesia, or CNS disorder or diseases, selected from the group consisting of addiction to drugs and chemical substances including cocaine,
amphetamine, ethanol and nicotine, anxiety, attention-deficit-/hyperactivity disorder (ADHD), autism spectrum disorder, catalepsy, cognition disorder, learning, memory and attention deficit, depression, encephalitis, epilepsy, headache disorder, insomnia, locked-in-syndrome, meningitis, migraine, multiple sclerosis (MS), leukodystrophies, amyotrophic lateral sclerosis (ALS), myelopathy, narcolepsy, neurodegenerative disease, traumatic brain injury, Alzheimer disease, Gaucher's disease, Huntington disease, Parkinson disease, Tourette's syndrome, psychotic condition, bipolar disorder, schizophrenia or paranoia.”
However, neither the specification, nor the claim, explicitly limits the invention to any specifically disclosed or recited embodiments, including, but not limited to, the above listed diseases and conditions. Consequently, the method for the treatment or prophylaxis of a sigma receptor related disease or condition, the method comprising administering a compound of formula (I) has been rendered indefinite by the use of the reach-through protocol.
The examiner suggests amending the claim, particularly as stated in the section above entitled Claim Rejections - 35 U.S.C. § 112(a), to overcome this rejection.
Conclusion
Claims 16-26 and 30-35 are rejected.
Claims 27-29 are objected to.
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.
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/R.M.S./Examiner, Art Unit 1624
/JEFFREY H MURRAY/Supervisory Patent Examiner, Art Unit 1624