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 .
DETAILED ACTION
Claims 1-31 are pending in the instant application.
Claim 22 is cancelled.
Claims 1-21 and 23-31 are examined herein.
Priority
The instant application claims benefit of foreign priority to GB2016492.7, filed on 16 October 2020, GB2111344.4, filed on 080 August 2021, and the benefit of priority to PCT/EP2021/078716, filed on 15 October 2021. The claims to the benefit of priority are acknowledged. As such, the effective filing date of the claims is 16 October 2020.
Information Disclosure Statement
No information disclosure statement (IDS) submitted by applicant.
Claim Interpretation
Claim 11 is directed to a composition; as such, the intended use (i.e. for use as a medicament) does not alter the chemical structure(s) of composition and is therefore not further limiting. See MPEP 2111.02.II:
[S]tatements in the preamble reciting the purpose or intended use of the claimed invention must be evaluated to determine whether or not the recited purpose or intended use results in a structural difference (or, in the case of process claims, manipulative difference) between the claimed invention and the prior art. If so, the recitation serves to limit the claim. See, e.g., In re Otto, 312 F.2d 937, 938, 136 USPQ 458, 459 (CCPA 1963) (The claims were directed to a core member for hair curlers and a process of making a core member for hair curlers. The court held that the intended use of hair curling was of no significance to the structure and process of making.); In re Sinex, 309 F.2d 488, 492, 135 USPQ 302, 305 (CCPA 1962) (statement of intended use in an apparatus claim did not distinguish over the prior art apparatus). To satisfy an intended use limitation which is limiting, a prior art structure which is capable of performing the intended use as recited in the preamble meets the claim. See, e.g., In re Schreiber, 128 F.3d 1473, 1477, 44 USPQ2d 1429, 1431 (Fed. Cir. 1997) (anticipation rejection affirmed based on Board’s factual finding that the reference dispenser (a spout disclosed as useful for purposes such as dispensing oil from an oil can) would be capable of dispensing popcorn in the manner set forth in appellant’s claim 1 (a dispensing top for dispensing popcorn in a specified manner)) and cases cited therein.
Claim Objections
Claims 2, 3, 6, 7, 12, and 13 are objected to because of the following informalities:
The following terms are capitalized, which implies they are trademarked. The compounds are not trademarked and do not require capitalization. 5-Hydroxytryptophan (5-HTP) (Oxitriptan), Tryptophan (L-Tryptophan), O-Tryptophan, 2-Hydroxy-Tryptophan, lmino-Tryptophan, lndoximod, 1-hydroperoxy-L-tryptophan, Tryptophanamide, 7-Aza-L-tryptophan, and Oglufanide
Appropriate correction is required.
Claim 14 is objected to because of the following informalities:
The claim recites; “…wherein the ergot alkaloid comprised ergoloid mesylates.” Comprise shold not be in the past tense. The claims should read; “…wherein the ergot alkaloid comprises ergoloid mesylates.
Appropriate correction is required.
Applicant is advised that should claim 10 be found allowable, claim 11 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 10-11, 13 and 15 rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more. Claims 10-11, 13 and 15 are directed to a natural product. The Examiner has followed the guidance set forth in MPEP 2106 and has concluded that the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception.
MPEP § 2106 sets forth the Subject Matter Eligibility Test to determine if a claim is directed to patent eligible subject matter.
Eligibility Step 1: The Four Categories of Statutory Subject Matter
As described in MPEP § 2106.03, Step 1 of the eligibility analysis asks: Is the claim to a process, machine, manufacture or composition of matter? The claims recite a naturally occurring composition, a combination one or tryptophans and one or more ergot alkaloids, set forth in independent claim 10. Accordingly, the answer to the question of Step 1 is Yes, because claims 10-11, 13 and 15 are considered directed to a composition of matter, which is eligible subject matter.
Eligibility Step 2A: Whether a Claim is Directed to a Judicial Exception
Step 2A, Prong One
Step 2A, Prong One asks if the claim recites a natural phenomenon. In the instant case, the compound of claim 10 is recited as a combination one or tryptophans and one or more ergot alkaloids. The characteristics of this compound are not markedly different from the naturally occurring counterpart in its natural state, because as claimed it has the identical chemical structure as it has in nature. Ergot alkaloids are biosynthetically derived from tryptophan in the genus Claviceps (Lorenz et al. Appl Environ Microbiol. 2007;73(22):7185–719). Therefore this genus of fungi is composed of both tryptophan and one or more ergot alkaloids.
MPEP § 2106.04(b) states that “When a claim recites a nature-based product limitation, examiners should use the markedly different characteristics analysis discussed in MPEP § 2106.04(c) to evaluate the nature-based product limitation and determine the answer to Step 2A.” MPEP 2106.04 (c)(I) states that “if the nature-based product limitation is naturally occurring, there is no need to perform the markedly different characteristics analysis because the limitation is by definition directed to a naturally occurring product and thus falls under the product of nature exception.”
In the instant case, the nature-based product of a combination one or tryptophans and one or more ergot alkaloids has the identical structure that it has in nature for the reasons outlined above. Accordingly, there is no need to perform the markedly different characteristics analysis, because the limitation is by definition directed to a naturally occurring product and is not markedly different from what occurs in nature.
Therefore, the answer to the question of Step 2A, Prong One is Yes, because claims 10-11, 13 and 15 are considered directed to a product of nature.
Step 2A, Prong Two
Step 2A, Prong Two, asks if the claim recites additional elements that integrate the judicial exception into a practical application. In the instant case, the judicial exception is not integrated into a practical application because the claims merely recite the compound and its properties without reciting any additional steps or elements that rely on or use the compound for any practical purpose.
Eligibility Step 2B: Whether a Claim Amounts to Significantly More
As described in MPEP 2106.05, Step 2B asks if claims recite additional elements that amount to significantly more than the judicial exception. In the instant case, the claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception, because there are no “additional elements” required by the present claims since they are directed only to the naturally occurring substance itself. The limitations set forth in dependent claims [insert] are [insert product or product by process] claims which are directed to the product itself and do not require any “additional elements”.
Thus, the answer to Step 2B is No. Therefore, claims 10-11 and 13-15 are not directed to patent eligible subject matter.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-9, 17-21 and 23-31 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 the treatment autism fails to provide the required enablement for prevention or prophylaxis of autism. 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. As the dependent claims do not remedy the issue they are also subject to the rejection.
To be enabling, the specification of the patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated:
The test is not merely quantitative, since a considerable amount of experimentation is permissible, if it is merely routine, or if the specification in question provides a reasonable amount of guidance with respect to the direction in which the experimentation should proceed to enable the determination of how to practice a desired embodiment of the claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
the nature of the invention
the state of the prior art
the predictability of the art
the amount of direction or guidance provided
the presence or absence of working examples
the breadth of the claims
the quantity of experimentation necessary
the relative skill of those in the art
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The nature of the invention – The instant claims are drawn to a method for the treatment, management or amelioration of FMR1 mediated autism (claim 1), Fragile X Syndrome (FXS) (claim 5), or diseases where autism is a known component (claim 17). In turning to the specification, Applicant defines treatment on page 5 as:
“…obtaining a desired pharmacologic and/or physiologic effect. The effect can be prophylactic in terms of completely or partially preventing a disease or symptom thereof and/or can be therapeutic in terms of a partial or complete cure for a disease and/or adverse effect attributable to the disease. "Treatment" as used herein, covers any treatment of a disease in a mammal, particularly in a human, and includes: (a) preventing the disease from occurring in a subject which can be predisposed to the disease but has not yet been diagnosed as having it; (b) inhibiting the disease, i.e., arresting or slowing its development; and (c) relieving the disease, i.e., causing regression of the disease.”
The state of the prior art - the pharmacological art requires the screening of potential drug candidates in vitro and in vivo to determine if the drug candidates exhibit the desired pharmacological activities.
In order to treat a disease: one would need to precisely identify what the disease is, identify what biological target is connected with the disease, demonstrate that the drug candidate in some way modulates the normal processes of the biological target, and demonstrate that a patient benefited from such modification without detrimental side effects. Typically, this process includes in vitro laboratory screening, preclinical in vivo screening, and three phases of clinical trials. Once this arduous process has been successfully completed by a drug candidate, subsequent drug candidates will benefit from the established proof of concept. The subsequent drug candidates must demonstrate a substantial correlation between their biological activity and that of the known drug candidate.
In order to prevent a disease: one would need to precisely identify those subjects likely to acquire such a disease, administer Applicant’s claimed invention, and demonstrate that the patient did not develop the disease as a result of the administration of the claim invention.
In the instant case, the prior arts recognize that therapeutic agents have potential to treat symptoms of autism, but not prophylactically treat or prevent autism (Hanson et al. Intractable Rare Dis Res. 2014;3(4):110–117).
The predictability or unpredictability of the art – the law recognizes the pharmaceutical art as an unpredictable art and requires each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18 24 (CCPA 1970). Accordingly, the more unpredictable an area is the more specific disclosure is necessary in order to satisfy the statute. Section 2164.02 of the MPEP provides:
"[C]orrelation” as used herein refers to the relationship between in vitro and in
vivo animal model assays and a disclosed or a claimed method of use . . . if the
art is such that a particular model is recognized as correlating to a specific
condition, then it should be accepted as correlating unless the examiner has
evidence that the model does not correlate.
In light of these remarks, the Examiner finds that one of ordinary skill in the art would agree with the court; that is, the pharmaceutical art is unpredictable. Thus, a substantial correlation is necessary for establishing the potential of new therapeutics.
The amount of direction or guidance presented – the instant specification provides an explanation of the biological activity of the FMR1 gene on page 1. The specification does not provide an explanation as to link the function of tryptophan and its derivatives in the treatment of FMR1 mediated diseases, but demonstrates their treatment in FMR1 knockout mice. 5-Hydroxytryptophan (5-HTP), or oxitriptan, is discussed as a metabolic intermediate in the synthesis of serotonin (page 15, line 12), and sumatriptan (used in the instant assays) is a known serotonin agonist. There is no direction or guidance provided that supports a use of a tryptophan derivative for preventing FMR1 mediated autism or FXS.
The amount of guidance or direction to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. MPEP § 2164.03 (quoting In re Fisher, 427 F.2d 833, 839, 166 USPQ 18 24 (CCPA 1970)). As identified supra, the pharmaceutical art is recognized as unpredictable.
Thus, in order to support a claim for preventing FXS or FMR1-mediated autism a vast amount of evidence is required because such a claim is not supported by the prior art or the instant specification.
The presence or absence of working examples - there are no working or prophetic examples in the specification that demonstrate that the instant compounds or compositions thereof may prophylactically treat and prevent FMR1-mediated autism or FXS The assays in the specification demonstrate that the instant compounds were tested for their ability to treat symptoms.
The breadth of the claims – is incommensurate in scope with the disclosure because a fair reading of the specification fails to support a finding that the tryptophan and its derivates may prevent FMR1-mediated autism or FXS in a patient.
The quantity of experimentation necessary – generally speaking, the amount of experimentation to transform a molecule into medicine is vast and the success thereof is low. Recent statistics indicate that the attrition rates during drug development remain high. Schafer et al. Drug Discovery Today 2008, 13 (21/22), 913-916. The article makes clear that there are many steps necessary to promote a new molecular entity toward its clinical use, any one of which is cumbersome.
For instance, Schafer et al. discloses: "proof of concept trials have failed when the decision to enter clinical development was based on preclinical experiments using the wrong compound, the wrong experimental model, or the wrong endpoint.” It can be gleaned from this article that a plethora of experimentation is needed to identify the lead compound (i.e. one among many in a Markush-type claim), to establish which preclinical tests are predictive of clinical success, and to establish which diseases are the best to target for each lead compound.
There is generally a vast amount of experimentation to take a drug from bench to the clinic. See e.g., Horig et al. Journal of Translational Medicine 2004, 2(44) (“Successful drug development requires satisfying a matrix of domains from relevance to the disease and the drug-ability of the target through feasibility and convenience of drug delivery, demonstration of favorable benefit-risk profile in order to achieve a drug label that reflects physician and patent acceptance.") The Examiner finds that one of ordinary skill in the art would agree with the statements in these articles; that is, the amount of experimentation required to enable a pharmaceutical drug is extensive.
The level of skill in the art - the level of ordinary skill in the art may be found by inquiring into: (1) the type of problems encountered in the art; (2) prior art solutions to those problems; (3) the rapidity with which innovations are made; (4) the sophistication of the technology; and (5) the education level of active workers in the field. Custom Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 855, 962 (Fed. Cir. 1986). All of those factors may not be present in every case, and one or more of them may predominate. Envtl. Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983).
Based on the typical education level of the active workers in the field of pharmaceuticals and/or medicine, as well as the high degree of sophistication required to solve problems encountered in the art, the Examiner finds that a person of ordinary skill in the art would have at least a college degree in a field related to medicine and/or the pharmaceutical art and at least four years of work experience, i.e. a masters or doctorate level scientist/clinician.
Therefore, claims 1-9, 17-21 and 23-31 are rejected because the Examiner finds that the Wands factors suggest a conclusion that the skilled artisan would not be able to make and use the instant invention without undue experimentation, although the level of skill for an ordinary person in the art is high. That is, due to the breadth of the claims, the unpredictability of the art, the lack of guidance or direction from the disclosure, the lack of any working examples, and the amount of experimentation needed illustrate that a person having ordinary skill in the art would not be able to prevent FMR1-meidated autism or FXS
Claims 1, 3-11, 13-21 and 23-31 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. As the dependent claims do not remedy the issue they are also subject to the rejection.
Claim 1 is directed to a method for the treatment, management, or amelioration of FMR1-mediated autism comprising administering a therapeutically effective amount of a medicament comprising one or more tryptophans or derivatives. A “therapeutically effective amount” is a functional limitation which requires a compound to obtain “… a desired pharmacologic and/or physiologic effect” (page 5, line 17). The Applicant’s disclosure does not provide sufficient written description to support this functional limitation.
See MPEP 2163 II. A. 3. (a) (ii) with regards to the requirements for descriptive support and for functional limitations of generically described entities:
“The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406”
“A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.”
There is no structure-function relationship for all tryptophans and their derivatives for treating FMR1-mediated autism or FXS. Tryptophan derivatives are undefined by the specification, therefore the bounds of what is and what is not a derivative is unknown. For example, ergot alkaloids are tryptophan derivatives, but the instant claims treat these derivatives as a class separate from tryptophan derivatives. Therefore, without the structural bounds of a tryptophan derivative there can be no correlation to function. The art teaches diverse function for tryptophan derivatives such as anticancer properties, antibiotic properties, immunosuppressant properties, antifungal properties, and phytotoxic properties (Romney et al. J. Am. Chem. Soc. 2017;139:10769−10776). Within the human body tryptophan derivatives also have diverse functions and structures. By the serotonin pathway tryptophan is derived into oxitriptan, serotonin, and melatonin. By the kynurenine pathway tryptophan is derived into N-formyl-kynurenine, kynurenine, and niacin. (Barik. Int J Mol Sci. 2020;21(22):8776).
Additionally the specification does not provide an adequate representation of all the possible tryptophans and tryptophan derivatives. Applicant provides two derivatives, oxitriptan, and sumatriptan. Failure to represent all the all the possible species of tryptophans and tryptophan derivatives through relationship of structure and function, which would provide an overall depiction of the claimed subject matter, suggests the applicant is not in possession of the claimed invention.
To summarize, there is a lack of descriptive support since the claims recite a functional limitation and: (i) the provided species are not sufficiently representative of the genus of compounds having such function, (ii) multiple other species are known in the art with completely different structural and functional features and (iii) there is no general art-recognized structure-function relationship for compounds with the required functional activity.
Claims 10-15 and 17-31 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. As the dependent claims do not remedy the issue they are also subject to the rejection.
Claim 10 is directed to a composition of one or more tryptophans or derivatives and one or more ergot alkaloids, derivatives, or mimetics thereof. Claim 17 is directed to the method for the treatment , management, or amelioration of an autism disease comprising administering a therapeutically effective amount of a medicament comprising the combination of one or more tryptophans or derivatives and one or more ergot alkaloids, derivatives or mimetics. A “therapeutically effective amount” is a functional limitation which requires a compound to obtain “… a desired pharmacologic and/or physiologic effect” (page 5, line 17). The Applicant’s disclosure does not provide sufficient written description to support this functional limitation.
See MPEP 2163 II. A. 3. (a) (ii) with regards to the requirements for descriptive support and for functional limitations of generically described entities:
“The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406”
“A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.”
There is no structure-function relationship for all ergot alkaloids, derivatives, or mimetics. Ergot alkaloids are taught by the art to be a large family of indole derivatives with both diverse structures and biological activity (Wallwey. Nat. Prod. Rep. 2011;28:496). Ergot alkaloid derivatives and mimetics are both undefined by the specification, therefore the bounds of what is and what is not an ergot alkaloids derivatives or mimetics is unknown. Without the structural bounds of an ergot alkaloids derivatives or mimetics there can be no correlation to function.
Additionally the specification does not provide an adequate representation of all the possible ergot alkaloids derivatives or mimetics. Applicant provides one example of an ergot alkaloid; a mixture of dihydroergocornine, dihydroergocristine, and dihydroergocryptine, known as ergoloid mesylates. Failure to represent all the all the possible species of ergot alkaloids, derivatives, or mimetics through relationship of structure and function, which would provide an overall depiction of the claimed subject matter, suggests the applicant is not in possession of the claimed invention.
To summarize, there is a lack of descriptive support since the claims recite a functional limitation and: (i) the provided species are not sufficiently representative of the genus of compounds having such function, (ii) multiple other species are known in the art with completely different structural and functional features and (iii) there is no general art-recognized structure-function relationship for compounds with the required functional activity.
Claim Rejections - 35 USC § 112
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 1-21 and 23-31 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.
Claim 1 is directed to a method for the treatment, management, or amelioration of FMR1-mediated autism comprising administering a therapeutically effective amount of a medicament comprising one or more tryptophans or derivatives. The term “one or more tryptophans” is unclear. There is one structure associated with tryptophan, unless the plurality of the term is supposed to refer to the two isomers of tryptophan. Additionally, the term “derivative” renders the claim indefinite. There is no definition provided as to the bounds of a tryptophan derivative. And “amelioration” is a relative term. The specification does not define the term nor how it can be quantified. As the dependent claims do not remedy the situation they are also subject to the rejection.
Claim 5 is directed to a method for the treatment, management, or amelioration of Fragile X Syndrome comprising administering a therapeutically effective amount of a medicament comprising one or more tryptophans or derivatives. The term “one or more tryptophans” is unclear. There is one structure associated with tryptophan, unless the plurality of the term is supposed to refer to the two isomers of tryptophan. Additionally, the term “derivative” renders the claim indefinite. There is no definition provided as to the bounds of a tryptophan derivative. And “amelioration” is a relative term. The specification does not define the term nor how it can be quantified. As the dependent claims do not remedy the situation they are also subject to the rejection.
The term “about” in claim 8 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 10 is directed to a composition comprising the combination of one or more tryptophans or derivatives thereof and one or more ergot alkaloids, derivatives, or mimetics thereof. The term “one or more tryptophans” is unclear. There is one structure associated with tryptophan, unless the plurality of the term is supposed to refer to the two isomers of tryptophan. Additionally, the terms “derivative” renders the claim indefinite. There is no definition provided as to the bounds of a tryptophan derivative or an ergot alkaloid derivative. As the dependent claims do not remedy the situation they are also subject to the rejection.
The term “substantially” in claim 16 is a relative term which renders the claim indefinite. The term “substantially” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 17 is directed to a method for the treatment, management, or amelioration of an autism disease or disease where autism is a known component the combination of one or more tryptophans or derivatives thereof and one or more ergot alkaloids, derivatives, or mimetics thereof. The term “one or more tryptophans” is unclear. There is one structure associated with tryptophan, unless the plurality of the term is supposed to refer to the two isomers of tryptophan. Additionally, the term “derivative” renders the claim indefinite. There is no definition provided as to the bounds of a tryptophan derivative or an ergot alkaloid derivative. And “amelioration” is a relative term. The specification does not define the term nor how it can be quantified. As the dependent claims do not remedy the situation they are also subject to the rejection.
Claim 23 is directed to the method of claim 17 wherein the autism or disease where autism is a known component is a behavioral disorder. This is unclear as autism is not a behavioral disorder but a neurodevelopmental disorder that can present with behavioral problems or disorders. For the purpose of examination the claim is interpreted as the behavioral disorder is a comorbidity.
The term “about” in claim 29 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 11 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. As the intended use is not further limiting, claim 11 does not add any limitations to claim 10. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claims 1, 2, 4-6, 8-21 and 23-31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 4, 5, 8, 9, 13-20, and 22-30 of co-pending Application No. 18249229 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other as the reference application is directed to species of the instant genus.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Regarding claim 1, the reference application recites a method for the treatment, management or amelioration of FMR1 mediated autism comprising, administering a therapeutically effective amount of a medicament comprising one or more triptans or derivatives thereof to an individual in need of such treatment, management or amelioration (claim 1). Triptans are a derivative of tryptophan.
Regarding claim 2, the reference application recites one or more triptans, which would include oxitriptan (claim 1).
Regarding claim 4, the reference application recites wherein the FMR1 mediated autism is related to Fragile X Syndrome (FXS) (claim 4).
Regarding claim 5, the reference application recites a method for the treatment, management or amelioration of FXS comprising, administering a therapeutically effective amount of a medicament comprising one or more triptans or derivatives thereof to an individual in need of such treatment, management or amelioration (claim 5). Triptans are a derivative of tryptophan.
Regarding claim 6, the reference application recites one or more triptans, which would include oxitriptan (claim 1).
Regarding claim 8, the reference teaches the administration of the composition in a daily dose in the range of about 50 mg to about 100 mg (claim 8), which overlaps with the instant range.
Regarding claims 10-12, the reference application recites a composition comprising the combination of one or more triptans or derivatives thereof and one or more ergot alkaloids, derivatives or mimetics thereof (claim 9). The intended use of claim 11 is not further limiting.
Regarding claim 14, the reference application recites the ergot alkaloids are ergoloid mesylates (claim 13).
Regarding claim 15, the reference application recites wherein the ergot alkaloid derivatives and mimetics are selected from one or more of the following: methysergide; dihydroergotamine; lisuride ergotamine nicergoline; dihydroergocristine; dihydroergocornine; dihydroergocryptine; ergometrine; methylergometrine; cabergoline; pergolide; bromocriptine; lysergic acid diethylamide; terguride; and metergoline (claim 14).
Regarding claim 16, the reference application recites wherein the ergot alkaloid derivatives and mimetics comprises a substantially equiproportional preparation of dihydroergocornine, dihydroergocristine, and dihydroergocryptine (claim 15).
Regarding claim 17, the reference application recites a method for the treatment, management or amelioration of an autism disease or disease where autism is a known component comprising, administering a therapeutically effective amount of a medicament comprising a combination of one or more triptans or derivatives thereof and one or more ergot alkaloids, derivatives or mimetics thereof to an individual in need of such treatment, management or amelioration (claim 16).
Regarding claim 18, the reference application recites wherein the autism disease or disease where autism is a known component is one of the following: 1 p21.3 microdeletion syndrome; adenylosuccinate lyase deficiency; autism-facial port-wine stain syndrome; autism spectrum disorder due to AUTS2 deficiency; autism spectrum disorder-epilepsy-arthrogryposis syndrome; developmental delay with autism spectrum disorder and gait instability; inverted duplicated chromosome 15 syndrome; macrocephaly-intellectual disability-autism syndrome; severe neurodevelopmental disorder with feeding difficulties-stereotypic hand movement bilateral cataract; Smith-Magenis syndrome; tuberous sclerosis complex; Xq12-q13.3 duplication syndrome (claim 17).
Regarding claim 19, the reference application recites wherein the autism disease or disease where autism is a known component is one of the following: Asperger syndrome, atypical autism and autistic disorder (claim 18).
Regarding claim 20, the reference application recites wherein the autism is FMR1 mediated Autism (claim 19).
Regarding claim 21, the reference application recites wherein the autism is related to FXS (claim 20).
Regarding claim 23, the reference application recites wherein the autism or disease where autism is a known component is a behavioral disorder (claim 22).
Regarding claim 24, the reference application recites wherein the behavioral disorder is one of the following: hyperactivity, social anxiety, memory loss and/or disruptive behavior (claim 23).
Regarding claim 25, the reference application recites wherein the behavioral disorder is one of the following: attention deficit and hyperactivity disorder; stereotypic movement disorder; conduct disorder; generalized anxiety disorder; neurotic disorder; obsessive-compulsive disorder; agoraphobia; social phobia; separation anxiety disorder and 15q11q13 microduplication syndrome (claim 24).
Regarding claim 26, the reference application recites wherein the one or more triptans or derivatives thereof and the one or more ergot alkaloids, derivatives or mimetics thereof are in a mixture (claim 25).
Regarding claim 27, the reference application recites wherein the medicament comprising the one or more triptans or derivatives thereof is for administration separately, together or sequentially with the one or more ergot alkaloids, derivatives or mimetics thereof (claim 26).
Regarding claim 28, the reference application recites sumatriptan and an ergoloid mixture, and wherein the medicament is administered in a daily dose in the range of about 50 mg to about 100 mg of
sumatriptan and in the range of about 1 mg to about 3 mg of ergoloid mixture (claim 27). The reference application teaches sumatriptan instead of the instant oxitriptan recitation. However, as both are triptans, and the reference application teaches all triptans, it would be prima facie obvious to substitute one triptan for the another.
Regarding claim 29, the reference application recites the method comprising sumatriptan and ergoloid mesylates, wherein the medicament is administered in a dose of about 20 mg to about 100 mg TID of sumatriptan and a dose of about 1 mg TID of ergoloid mesylates (claim 28). The reference application teaches sumatriptan instead of the instant oxitriptan recitation. However, as both are triptans, and the reference application teaches all triptans, it would be prima facie obvious to substitute one triptan for the another.
Regarding claim 30, the reference application recites wherein the medicament further comprises a pharmaceutically acceptable carrier, excipient, or diluent (claim 29).
Regarding claim 31, the reference application recites wherein the medicament further comprises an SSRI (claim 30).
Claim Rejections - 35 USC § 102
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 (i.e., changing from AIA to pre-AIA ) 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1, 2, 4, 8-9 and 30 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Wood et al. (WO 2021081376 A1).
Regarding claims 1 and 2, Wood discloses a method of treating the symptoms associated with autism spectrum disorder (ASD) comprising administering an effective amount of a triptan to a patient (claim 1). A triptan is a tryptophan derivative. In the absence of evidence to the contrary, ASD, as taught by Wood, would encompass autism mediated by FMR1.
Regarding claim 4, Wood teaches the method of treating ASD, this would encompass autism related to Fragile X Syndrome (claim 1). In the absence of evidence to the contrary, ASD, as taught by Wood, would encompass FXS.
Regarding claim 8, Wood teaches the method comprising administering 1 mg to 200 mg daily (paragraph [0054]).
Regarding claim 9, Wood teaches the composition can be administered three times a day (paragraph [0057]).
Regarding claim 30, Wood teaches the method of administering the composition comprising a pharmaceutically acceptable carrier, excipient, or diluent (paragraph [0026]).
Claim(s) 10-11, 13 and 15 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Lorenz et al. (cited above).
Regarding claims 10 and 11, Lorenz teaches ergot alkaloids are biosynthetically derived from tryptophan in the genus Claviceps (page 7185). Therefore this genus of fungi is composed of both tryptophan and one or more ergot alkaloids. The intended use is not further limiting.
Regarding claim 13, Lorenz teaches tryptophan (Fig. 1).
Regarding claim 15, Lorenz teaches lysergic acid (Fig. 1).
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 (i.e., changing from AIA to pre-AIA ) 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1, 2, 4-6, 8-9 and 30-31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wood (cited above) in view of Hanson et al. (Intractable Rare Dis Res. 2014;3(4):110–117).
The teachings of Wood are disclosed above and incorporated by reference herein.
Regarding claims 5 and 6, Wood teaches a method of treating the symptoms associated with autism spectrum disorder (ASD) comprising administering an effective amount of a triptan to a patient (claim 1). A triptan is a tryptophan derivative. Wood explains triptans have selective activity on the serotonin system (paragraph [0027]), which has been implicated in the pathophysiology of autism (paragraph [0028]).
Wood does not teach the treatment of Fragile X Syndrome.
Hanson teaches significant overlap between autism and FXS, as FXS is the leading monogenetic cause of autism (page 111, column 1). Additionally Hanson teaches serotonin dysregulation in patients with autism and highlights decreased metabolism of tryptophan in these patients (page 111, column 1).
As Wood teaches treating autism symptoms by targeting the serotonin system and Hanson teaches the link between autism, FXS, and the serotonin system, it would be prima facie obvious to one of ordinary skill in the art to apply the method of treating taught by Wood to the patient population taught by Hanson. The skilled artisan would be motivated to combine the teachings due to FXS being the leading genetic cause of autism and the shared serotonin dysregulation. Hanson communicates early success with improving symptoms of FXS by targeting the serotonin system (page 115, column 1) that would suggest to one skilled in the art a reasonable expectation of success.
Regarding claim 31, Hanson teaches administering an SSRI. As both triptans and SSRIs target the same pathway it would be prima facie obvious to combine them.
Claim(s) 1-9 and 30-31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wood (cited above) in view of Hanson et al. (cited above) and in further view of Höglund et al. (Front. Endocrinol.2019;10(158):1-11).
The teachings of Wood and Hanson are disclosed above and incorporated by reference herein.
The combination of Wood and Hanson do not teach tryptophan or tryptophan derivatives other than triptans. Hanson does teach tryptophan metabolism is decreased in patients with autism and symptoms worsen when tryptophan is removed from the patient’s diet.
Regarding claims 2, 3, and 7, Höglund teaches that tryptophan is the precursor to serotonin. 5-Hydroxytyrptophan (oxitriptan) is the intermediate compound in the biosynthetic pathway to tryptophan. As such, these compounds are involved in the serotonin pathway.
In KSR International Vo. V. Teleflex Inc., 82 USPQ2d (U.S. 2007), the Supreme Court particularly emphasized “the need for caution in granting a patent based on a combination of elements found in the prior art,” (Id. At 1395) and discussed circumstances in which a patent might be determined to be obvious.
In this case at least prong B of KSR applies – substitution of one known element for another. As Wood teaches compounds that target the serotonin pathway and are tryptophan derivatives, it would be prima facie obvious to one skilled in the art to substitute a triptan with tryptophan.
Thus, all of the elements of claims were known to one of ordinary skill in the art at the time the invention was made and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art at the time of invention. Therefore, the claimed invention, as a whole, would have been obvious to one of ordinary skill in that art at the time the invention was made.
Claim(s) 1, 2, 4-6, 8-9, 17-21, and 26-31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wood (cited above) in view of Hanson et al. (cited above) and in further view of Schiff (Am J Pharm Educ. 2006;70(5):98).
The teachings of Wood and Hanson are disclosed above and incorporated by reference herein.
Regarding claim 17, the combination of Wood and Hanson teach administering a tryptophan derivative for the treatment of an autism disease of disease where autism is a known component.
The combined teaching does not teach administering an ergot alkaloid.
Schiff teaches ergot alkaloids, particularly ergotamine, shares the agonistic properties toward the serotonin 5-HT1B/1D receptors with the triptan drug class (page 6, column 2).
In KSR International Vo. V. Teleflex Inc., 82 USPQ2d (U.S. 2007), the Supreme Court particularly emphasized “the need for caution in granting a patent based on a combination of elements found in the prior art,” (Id. At 1395) and discussed circumstances in which a patent might be determined to be obvious.
In this case at least prong A of KSR applies – combining known compounds for the same purpose of targeting the serotonin pathway. It would be prima facie obvious to combine a tryptophan derivative an ergot alkaloid as both target the serotonin pathway. Additionally, ergot alkaloids themselves are tryptophan derivatives thus one skilled in the art would be directed to their use and have a reasonable expectation of success.
Thus, all of the elements of claims were known to one of ordinary skill in the art at the time the invention was made and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art at the time of invention. Therefore, the claimed invention, as a whole, would have been obvious to one of ordinary skill in that art at the time the invention was made.
Regarding claims 18-20, Wood teaches the treatment of ASD, this is a the general term that encompasses the individualized diagnosis recited in the instant claims.
Regarding claim 21, Hanson teaches FXS.
Regarding claims 26-29, the combined teachings teach the combination of active pharmaceutical ingredients. It would be routine optimization to determine the most efficacious order or administration and dosing.
Claim(s) 1, 2, 4-6, 8-9, 17-21, and 23-31 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wood (cited above) in view of Hanson et al. (cited above) and Schiff (cited above) and in further view of Kaat et al. (Research in Autism Spectrum Disorders.2013;7:1579–1594).
The teachings of Wood, Hanson and Schiff are disclosed above and incorporated by reference herein.
Regarding claims 23-26, the combined teachings do not explicitly address behavioral problems of patients with autism.
Kaat teaches behavioral disorders experienced by patients diagnosed with ASD (Abstract). This includes attention deficit hyperactivity disorder, social anxiety, and generalized anxiety.
As Kaat links behavioral disorders with ASD, it would be prima facie obvious to one of ordinary skill in the art to treat ASD wherein behavioral disorders are exhibited by the method taught in the combination of Wood, Hanson, and Schiff.
Conclusion
Claims 1-21 and 23-31 are rejected.
Claims 2, 3, 6, 7, 12, and 13 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jerica K Wilson whose telephone number is (703)756-4690. The examiner can normally be reached Monday-Friday 9:00-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at (571)270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.K.W./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621