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 .
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 1-6, 8, 9, 11, 13, 19, 22-24, 26, 30-33 and 39 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 test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosures in the application coupled with information known in the art without undue experimentation (United States v. Telectronics, Inc. 8 USPQD2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is required is a conclusion reached by weighing several factors. These factors were outlined in Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and again in In re Wands, 8 USPQQ2d 1400 (Fed. Cir. 1988) and include the following:
State of the prior art and level of predictability in the art: In spite of considerable interest in inducing immune tolerance for treatment of autoimmune disease, the art of record contains no description of methods of inducing such tolerance by preferentially delivering liposomes to the liver that comprise mRNA’s encoding the problematic protein (autoantigen) and wherein the nucleotides of said mRNAs are unmodified. Sahin et al (WO 2018/188730, of record) teach methods of inducing tolerance to an autoantigen by administration of liposomes comprising mRNAs that encode said autoantigen, but do not teach preferential delivery of such liposomes to the liver. Further, in the working examples Sahin et al relies upon modified nucleotides to render their mRNA “non-immunogenic”, which are excluded by the present claims. Horst et al (2016, of record) teach the tolerogenic potential of the liver regarding autoantigens, but do not teach preferentially delivery of liposomes to the liver, or other methods of inducing specific immune tolerance to a given autoantigen encoded by an mRNA. Thus, the art is silent with regard to methods of inducing immune tolerance to a given autoantigen by preferential delivery of liposomes to the liver, and wherein the nucleotides of mRNA’s encoding the autoantigen are unmodified.
This clearly evidences that induction of immune tolerance by preferential delivery of liposomal mRNA’s to the liver was at an early stage of development at the time of filing and that the skilled artisan would not know how to make and use such liposomes and mRNA’s that were operative to induce immune tolerance in a subject without explicit guidance from the specification or significant empirical experimentation.
Amount of direction provided by the inventor and existence of working examples: The working examples are entirely prophetic and provide no specific guidance on reducing the claimed invention to practice in vivo as claimed. The only figures in the specification are apparently adapted from Horst et al (2016, cited above). The specification also discloses well-known methods for preparing mRNA’s and liposomes.
Although the specification suggests a method by which one might attempt to express the claimed mRNA’s in a liver- or hepatocyte-specific manner by the introduction of miR’s that result in degradation of the mRNAs in antigen-presenting cells, there is no evidence that the method contemplated would actually produce immune tolerance in a subject. Nor is there any evidence that this would lead to liver-specific expression or preferential delivery of liposomes to the liver. Thus, in order to use the invention as claimed, the skilled artisan would have to further develop the methods of making and using liposomes and mRNA’s such that liposomes and mRNAs capable of functioning as recited in the claims could be constructed. In particular, the skilled artisan would have to further develop the preferential delivery of liposomes to the liver and liver-specific expression of mRNAs such that immune tolerance could be achieved.
Nature of the invention and Breadth of the claims: The claims are directed to methods of immune tolerance to any given protein or peptide, the properties of which have been outlined above. The claims are not limited to any particular liposome formulation, autoantigen, species or subject. Thus, the claims encompass a divergent genus of methods of inducing immune tolerance to any protein, in any host, using liposomes of any formulation and mRNAs of any sequence. As the claims encompass such a wide variety of methods, it is incumbent upon the disclosure to set forth the manner and process of making a variety of functional species that is commensurate with the scope of protection sought.
Relative skill of those in the art and quantity of experimentation needed to make or use the invention: Although the level of skill in the art of making mRNAs or liposomes is high, making those with the properties discussed here is low. One would not be able to induce immune tolerance in a subject via liposomal delivery of mRNA given no more than the teachings available at the time of filing without undue experimentation. The art of record does not provide a single working example of the claimed methods that is operative in any type of subject. Likewise, all of the teachings in the instant application are prophetic. Given the broad scope of the claims, the early developmental stage and the unpredictability of the art at the time of filing, making and using the claimed invention would clearly require undue experimentation. Therefore, the claims are properly rejected under 35 USC 112, first paragraph, as lacking enablement.
Given the above analysis of the factors which the courts have determined are critical in determining whether a claimed invention is enabled, it must be considered that undue and excessive experimentation would have to be conducted by the skilled artisan in order to practice the claimed invention.
Conclusion
No claim is allowed.
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/MICHAEL D BURKHART/Primary Examiner, Art Unit 1638