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
STATUS OF THE CLAIMS: Claims 1-5, 8-10, 12-14, 18, 21, 24, 26, 28, 31, 36-37, 44-47, 49, 51, 58, 64-66, 71-73, 82, and 90-91 are pending in this application.
Election/Restrictions
Applicant’s election of species without traverse in the reply filed on September 8, 2025 is acknowledged. All claims were examined.
Claim Rejections - 35 USC § 112, first paragraph
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 82 is 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.
Claim 82 is directed to a method of ameliorating, preventing, delaying onset or treating diseases associated with reduced activity of Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). In light of this, it can be asserted that in spite of the vast expenditure of human and capital resources in recent years, no one drug has been found which is effective in ameliorating, preventing, delaying onset or treating diseases associated with reduced activity of CFTR. In re Hokum, 226 USPQ 353 (ComrPats 1985).
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. In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404.
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) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.
The breadth of the claims
The breadth of the instant claims is seen to encompass methods for ameliorating, preventing, delaying onset or treating diseases associated with reduced activity of CFTR, by administering to a patient in need of such treatment a therapeutically effective amount of the composition of claim 1. Applicant fails to disclose which specific diseases are treated. Thus, the claims are extremely broad.
The nature of the invention
The nature of the invention is the treatment of these disorders through the use of the claimed compound and derivatives thereof. Currently, there are no known agents that treat these diseases all inclusively.
The level of predictability in the art
The treatment of these disorders is highly unpredictable. It is well established that “the 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).
The amount of direction provided by the inventor.
The applicant has not demonstrated sufficient guidance provided in the form of administration profiles, combination ratios of the active agents or reference to the same in the prior art to provide a skilled artisan with sufficient guidance to practice the instant treatment of disorders claimed. Further, the applicant discloses that an effective amount of the compound will be administered without providing any direction other than that the compounds of the invention have a high therapeutic index and follows this with a definition readily found in a basic pharmacology textbook. It should be noted that the therapeutic index of a drug in humans is almost never known and is only determined through clinical experience.
The existence of working examples.
There is not seen in the disclosure, sufficient evidence to support Applicant’s claims of treating of these disorders. 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. In re Wright, 27 USPQ2d 1510 (CAFC). The disclosure does not demonstrate sufficient evidence to support the applicant's claim to the treatment. There are not sufficient working examples or data from references of the prior art to provide a nexus between those examples and a method of treating the disorders with the claimed compound.
The level of one of ordinary skill.
The level of skill is that of one with a doctoral understanding of ameliorating, preventing, delaying onset or treating diseases associated with reduced activity of CFTR therapeutics. Applicant’s data is not convincing as to make the production and use of pharmaceutical compositions comprising the recited compounds feasible without undue, un-predictable experimentation.
The quantity of experimentation.
A great deal of experimentation is required for the method of treating these disorders. Furthermore, direction, in the form of examples, must be shown to determine what an effective dose may be. The references submitted do not demonstrate this. Therefore, one of ordinary skill in the art would require a significant amount of experimentation in order to determine the effective dosage to treat the multitudes of different types of diseases with the claimed compound individually or in combination with other therapeutic agents.
Thus, it can be safely concluded that the instant case fails to provide an enabling disclosure for ameliorating, preventing, delaying onset or treating diseases associated with reduced activity of CFTR.
Claim Rejections - 35 USC § 103
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 non-obviousness.
Claims 1-5, 8-10, 12-14, 18, 21, 24, 26, 28, 31, 36-37, 44-47, 49, 51, 58, 64-66, 71-73, 82, and 90-91 are rejected under 35 U.S.C. 103 as being unpatentable over Karve et al. (US Pub. 2020/0085745) in view of Padmanabh Chivukula et al. (WO2019/191780).
Applicant claims a composition in claims 1-5 and 8-10 comprising the following:
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Additionally, in dependent claims 2-5 and 8-10, Applicant claims the following:
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Karve discloses compositions comprising a lipid formulation and a mRNA encoding a peptide having CFTR activity wherein the lipid formulation encapsulates the mRNA. (See Abstract, and paragraphs [0005], [0019], [0075], [0106] , [0132], [0135], [0137], [0210], [0213] and [0231]
Karve does not explicitly disclose a composition comprising a lipid formulation comprising an ionizable cationic lipid having the structure of ATX-012.
Chivukula discloses lipid nanoparticles encapsulating mRNA wherein a component of the nanoparticle comprises the structure ATX-012. (See Abstract, and paragraphs [0005], [0067], [0090] and [0188]).
It would have been obvious to one having ordinary skill in the art at the time of the invention to modify the teachings of the compositions of Karve by including the ATX-012 structure as a cationic lipid in the formulation because the ionizable and cationic nature of ATX-012 as taught by Chivukula would have been capable of utilization as a lipid component of the lipid formulation as taught by Karve. All of the moieties are taught in the art. Therefore, one of ordinary skill in the art, confronted with designing a composition comprising a lipid formulation composition comprising a lipid formulation and a mRNA encoding a peptide having CFTR activity wherein the lipid formulation encapsulates the mRNA, would modify the teachings of Karve by including the ATX-012 structure as a cationic lipid in the formulation as taught by Chivukula since the ionizable and cationic nature of ATX-012 as taught by Chivukula would have been capable of utilization as a lipid component of the lipid formulation as taught by Karve to generate the composition claimed by Applicant. See In re Payne, 203 USPQ 245(CCPA 1979).
Since Applicant’s claims are prima facie obvious in view of the teachings of Karve and Chivukula, Applicant’s claims are obvious, and therefore, rejected under 35 U.S.C. 103.
Regarding claim 2, Karve and Chivukula in combination teaches Applicant’s composition and discloses that the lipid formulation is selected from the group consisting of a lipoplex, liposome, lipid nanoparticle, polymer-based carrier, exosomes, lamellar body, micelle and an emulsion. (See page Abstracts, Karve paragraphs [0075]-[0076]).
Regarding claim 3 Karve and Chivukula in combination teaches Applicant’s composition. (See page Abstracts, Karve paragraphs [0005], [0075] and [0137]). Karve does not disclose wherein the liposome is selected from the group of liposomes in Applicant’s claim 3. Chivukula discloses lipid nanoparticles encapsulating mRNA wherein the nanoparticles are unilamellar or multilamellar liposomes. (See paragraphs [0008] and [0049]. It would have been obvious to one of ordinary skill in the art at the time of the invention to have modified the discloser of Karve to provide wherein the liposomes is a unilamellar or multilamellar liposomes because the number of outer layers of a liposome (i.e., unilamellar or multilamellar), which serves as a nanoparticle capable of encapsulation of mRNA as taught by Chivukula would both have been expected to act in the capacity of the liposome as taught by Karve.
Regarding claim 4, Karve and Chivukula in combination teaches Applicant’s composition, (see page Abstracts and Karve paragraphs [0005], [0075] and [0137]), and Karve teaches wherein the lipid formulation is a lipid nanoparticle. (See Abstracts, and Karve paragraphs [0075]-[0076]).
Regarding claim 5, Karve and Chivukula in combination teaches Applicant’s composition, (see Abstracts and Karve paragraphs [0005], [0075] and [0137]), and Karve teaches wherein the lipid nanoparticles has a size of less than about 200 nm. (See paragraphs [0025] and [0036]).
Regarding claim 8, Karve and Chivukula in combination teaches Applicant’s composition, (see Abstracts and Karve paragraphs [0005], [0075] and [0137]), and Karve teaches wherein the lipid nanoparticles has a size of less than about 55 nm to about 90 nm. (See paragraphs [0025] and [0036]).
Regarding claim 9, Karve and Chivukula in combination teaches Applicant’s composition, (see Abstracts and Karve paragraphs [0005], [0075] and [0137]), and Karve teaches in paragraphs [0019], [0023], [0210] and [0213] wherein the helper lipid is a phospholipid.
Regarding claim 10, Karve and Chivukula in combination teaches Applicant’s composition, (See page Abstracts, Karve paragraphs [0005], [0075] and [0137]), and Karve teaches wherein the helper lipid is selected from the group consisting of DOPE, DMPC, DSPC,DMPG, DPPC and PC. (See paragraphs [0019], [0023], [0210] and [0213]).
Since Applicant’s claims are prima facie obvious in view of the teachings of Karve and Chivukula, Applicant’s claims are obvious, and therefore, rejected under 35 U.S.C. 103.
Claims 12-14, 18, 21, 24, 26, 28, 31, 36-37, 44-47, 49, 51, 58, 64-66, 71-73, 82, and 90-91 are rejected because the claims are dependent on a rejected claim or relate back to a rejected claim.
Conclusion
Claims 1-5, 8-10, 12-14, 18, 21, 24, 26, 28, 31, 36-37, 44-47, 49, 51, 58, 64-66, 71-73, 82, and 90-91 are pending in this application. Claims 1-5, 8-10, 12-14, 18, 21, 24, 26, 28, 31, 36-37, 44-47, 49, 51, 58, 64-66, 71-73, 82, and 90-91 are rejected. No claims are allowed.
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/PAUL V WARD/ Primary Examiner, Art Unit 1622