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 Claims
Claims 1-2, 4-10, 13-14 and 16-22 are pending in the instant application. Claims 2, 4-5, 8, 13-14 and 17-22 are amended and claims 3, 11-12 and 15 are cancelled via the amendment filed October 24th, 2024.
Priority
This is a 35 U.S.C. 371 National Stage filing of International Application No. PCT/GB2023/051034 filed April 20th, 2023, which claims priority under 35 U.S.C. 119(a-d) to GB2206076.8, filed April 26th, 2022. Receipt is acknowledged of papers submitted under 35 U.S.C. 119(a)-(d).
Information Disclosure Statement
The Information Disclosure Statement (IDS) filed October 2th, 2024 has been considered by the Examiner.
Claim Objections
Claim 16 is objected to because of the following informalities:
It is recommended that Application amend the claim to insert “the group consisting of” after “selected from” and “and” before the last depicted compound of the claim, to conform with proper Markush format.
Claim Rejections – 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 1-2, 4-10, 13-14 and 16-22 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 instant specification, while being enabling for the disclosed compounds, salts, hydrates, isomers or polymorphs thereof and compositions employed as treatment for a disease caused by Cryptosporidium, does not reasonably provide enablement for generation or use of solvates or prodrugs that would be metabolized in a host to generate the compounds claimed in the instant application along with prevention of a disease caused by cryptosporidiosis in a method of administering the compounds or compositions of the instant claims. The specification does not enable any person having ordinary skill 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.
Pursuant to In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988), one considers the following factors to determine whether undue experimentation is required: (1) The breadth of the claims, (2), The nature of the invention, (3) The state of the prior art, (4) The level of one of ordinary skill, (5) The level of predictability in the art, (6) The amount of direction provided by the inventor, (7) The existence of working examples and (8) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Nature of the invention:
The invention is drawn to a compound of formula I, or a veterinary or pharmaceutically acceptable, salt, hydrate, solvate, isomer, prodrug or polymorph thereof and methods of treatment or prevention of a disease caused by Cryptosporidium.
Breadth of the claims:
The claims are broadly directed at a compound of formula I, or a veterinary or pharmaceutically acceptable, salt, hydrate, solvate, isomer, prodrug or polymorph thereof and method of administering them for the prevention or treatment of a disease caused by Cryptosporidium.
Level of ordinary skill in the art:
The artisans using Applicant’s method 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.
The level of skill in the art is high; however, due to the unpredictability in the pharmaceutical art, it is noted that each embodiment of the invention is required to be individually assessed for physiological activity by in vitro or in vivo screening to determine which compounds exhibit the desired pharmacological activity and which diseases would benefit from this activity.
For example, a prodrug is a compound that is metabolized in the host to form the compound of the present disclosure. Specific prodrugs, however, are not disclosed, and the unpredictability of metabolites formed when a composition is administered requires the support of specific in vitro or in vivo screening to verify the formation of the disclosed compounds.
State of the prior art and predictability in the art:
With respect to the use of prodrugs, Walther et. al. (Adv. Drug Deliv. Rev., 2017, 65-77) represents the state of the prior art.
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 (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.
As such, without undue experimentation, a person having reasonable skill in the art would not be able to ascertain which prodrugs are reasonable due to the unpredictability of the formation of metabolites in the host.
Further, the prevention of a disease caused by Cryptosporidium is highly unpredictable. Innes et al (Trendsin Parasitology, March 2020, Vol. 36, No. 3) teaches that currently there are no effective vaccines to prevent cryptosporidiosis in humans or in livestock and there are few safe and effective therapeutic options available (page 291, paragraph 2).
The amount of direction provided and working examples:
The only direction or guidance present in the instant specification is the disclosure of results obtained by administration of the disclosed compounds. No examples of suitable solvates or prodrugs have been given.
Further, there are no examples in the specification that are concerned with prevention for a disease. Application fails to provide example showing the instant method could prevent the diseases caused by cryptosporidiosis. Therefore, the practitioner would turn to trial and error experimentations to make/use the instant compositions for preventing a disease caused by cryptosporidiosis. The examples of the specification show multiple days of treatment following infection. To prevent infection, the compound would need to function as a vaccine, and as seen from state of the prior art, this would be unpredictable and would require undue experimentation.
With regard to solvates, the present specification merely mentions the Applicant’s intention to make solvates, without teaching the preparation thereof. As stated in Morton International Inc. v. Cardinal Chemical Co., 28 USPQ2d 1190, 1194 (Fed.Cir. 1993):
The specification purports to teach, with over fifty examples, the preparation of the claimed compounds ... However ... there is no evidence that such compounds exist ... [T]he examples ... do not produce the postulated compounds ... [T]here is ... no evidence that such compounds even exist.
The same circumstance appears to be true here. There is no evidence that solvates of these compounds actually exist; if they did, they would have formed. Hence, applicants must show that solvates can be made, or limit the claims accordingly.
See MPEP 2164.01(a), discussed supra, justifying the conclusion of lack of enablement commensurate with the claims. Without guidance in the present application, undue experimentation will be required to practice Applicant’s claimed invention.
Quantity of experimentation needed to use the invention based on the content of the disclosure:
The quantity of experimentation needed is undue experimentation. As referenced above, a person having ordinary skill in the art would need to identify suitable prodrug candidates, determine the metabolites formed when said prodrugs are administered to a host, and evaluate the efficacy of these compounds in treating a disease caused by cryptosporidiosis.
Further, in the instant case, there isa substantial gap between treatment and prevention. Consequently, a burdensome amount of research would be required by one of ordinary skill in the art to bridge this gap. In order to utilize the compounds as claimed, the skilled artisan would be presented with an unpredictable amount of experimentation. An undetermined number of experimental factors utilizing a system for preventing a disease caused by cryptosporidiosis would have to be resolved by the practitioner and/or the patient. The disclosure is not sufficiently discussed in the specification to provide guidance to utilize the invention as claimed.
A conclusion of lack of enablement means that, based on the evidence regarding each of the above factors, the specification, at the time the application was filed, would not have taught one skilled in the art how to make and/or use the full scope of the claimed invention without undue experimentation.
The specification fails to provide enough support for the broad use of prodrugs and solvates of the claimed compounds along with the method of prevention.
Genentech Inc. v Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 states that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “patent protection is granted in return for enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”.
Therefore, in view of the Wands factors and In re Fisher (CCPA 1970) discussed above, to practice the claimed invention herein, a person having ordinary skill in the art would have to engage in undue experimentation to determine suitable prodrugs, solvates and method of prevention with the compounds and compositions in the instant claims, with no assurance of success.
Claim Rejections - 35 USC § 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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 22 is 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 22 recites “A pharmaceutical composition comprising a pharmaceutically acceptable salt, solvate, hydrate, isomer, prodrug, or polymorph thereof.” It is unclear what “thereof” is in reference to and ultimately, what the composition comprises.
Closest Prior Art
The closest prior art in terms of structural similarity to the instantly claimed compounds CAS Registry No. 1241722-77-9, which entered STN on September 16th, 2010.
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However, the compound has a hydrogen, where the instantly claimed compounds require R1, which can be -CH3, -CF2H or -CF3. As this piece of prior art is only a CAS registry compound, there is no motivation to make the necessary changes to arrive at the instantly claimed compounds of formula I.
Another piece of close prior art is Tang et al (WO 2023/104165 A1, which claimed priority to CN 202111493784.2, published August 12th, 2021). Tang teaches the following compound (claim 12):
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However, there are multiple differences between the prior art compound and the compound of the prior art. The prior art compound is not the proper R2 of the instant claims. Also, the R1 position of the prior art compound is not the required -CH3, -CF2H or -CF3. Tang does not teach the necessary motivation to make the changes to arrive at the instantly claimed compounds.
As such, the compounds as instantly claimed are novel and nonobvious.
Conclusion
No claim is allowed.
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/A.G.K./Examiner, Art Unit 1626
/FEREYDOUN G SAJJADI/Supervisory Patent Examiner, Art Unit 1699
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