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 1-12, 15-22 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 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims encompass cells comprising first and second CAR molecules (and methods of treatment using such) each with a different “spacer” and one with a “ligation-off inhibitory endodomain”, with the function of inhibiting the activating CAR signaling when unbound (or “ligation-off”) yet allowing activation (i.e. cell signaling) when bound, e.g. as recited in claim 1. According to the definitions in the specification, the CARs are not limited to any given spacer or ligation-off inhibitory endodomain.
However, applicant was not in possession of the claimed genera of CAR molecules with different spacers and “ligation-off inhibitory endodomains” as elements of the claimed products and methods in the absence of providing sufficient structural and functional characteristics of the genera of each of these elements broadly encompassed by the instant claim language, coupled with a known or disclosed correlation between function and structure.
However, the instant application has not provided a sufficient description showing possession of the necessary 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 genera of CAR molecules with different spacers and “ligation-off inhibitory endodomains” encompassing structurally related or structurally unrelated, functionally related or functionally unrelated molecules, equivalents and variants.
"It is not sufficient to define the recombinant molecule by its principal biological activity, e.g. having protein A activity, because an alleged conception having no more specificity than that is simply a wish to know the identity of any material with that biological property." Colbert v. Lofdahl, 21 USPQ2d, 1068, 1071 (BPAI 1992).
Mere idea or function is insufficient for written description; isolation and characterization at a minimum are required
The claims do not recited sufficient written description of the structural and functional characteristics coupled with a known or disclosed correlation between function and structure, since the disclosure fails to describe the common attributes or characteristics that identify each member of the genera of CAR molecules with different spacers and “ligation-off inhibitory endodomains” that inhibit the activating CAR, as broadly encompassed by the claimed invention.
Therefore, there is insufficient written description of the claimed genera of CAR molecules in the absence of defining the relevant identifying characteristics such as the structure or other physical and/or chemical characteristics of the claimed genera.
Further, the Court has interpreted 35 U.S.C. §112, first paragraph, to require the patent specification to “describe the claimed invention so that one skilled in the art can recognize what is claimed. Enzo Biochem, Inc. v. Gen-Probe Inc, 63 USPQ2d 1609 and 1618 (Fed. Cir. 2002). In evaluating whether a patentee has fulfilled this requirement, our standard is that the patent’s “disclosure must allow one skilled in the art ‘to visualize or recognize the identity of’ the subject matter purportedly described.” Id. (quoting Regents of Univ. of Cal. v. Eli Lilly & Co., 43 USPQ2d 1398 (Fed Cir. 1997)).
The Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement make clear that 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, reduction to drawings, 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 genus.
It is not sufficient to define a genus without sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, 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.
In the absence of sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, the claimed invention is not described in such a way as to reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed, had possession of the claimed invention.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the written description inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116.). Consequently, Applicant was not in possession of the instant claimed invention. See University of California v. Eli Lilly and Co. 43 USPQ2d 1398.
With respect to reliance upon screening for structural and/or functional equivalents, the Court has held that the disclosure of screening assays and general classes of compounds was not adequate to describe compounds having the desired activity: without disclosure of which peptides, polynucleotides, or small organic molecules have the desired characteristic, the claims failed to meet the description requirement of § 112. See University of Rochester v. G.D. Searle & Co., lnc., 69 USPQ2d 1886,1895 (Fed. Cir. 2004).
Applicant is relying upon certain biological activities and the disclosure of a limited number of species (e.g., two ligation-off inhibitory endodomains, CD45 and CD148) to support entire genera. The specification (Example 5) indicates the importance of the spacer domains, but only discloses two which are suitable to provide the claimed function when incorporated into the CAR molecules of the claims, a CD8 “stalk” and an IgG heavy chain spacer.
The problem here is that the instant specification fails to provide a sufficient disclosure of
each of the different spacers and “ligation-off inhibitory endodomains” of the claimed products in order for the CAR molecules to retain the appropriate structural and functional requirements of inhibiting the activating CAR when desired, as broadly encompassed by the claimed invention.
A skilled artisan cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genera that exhibit the appropriate structural and functional elements for inhibiting the activating CAR when “ligation-off”.
It has been well known that minor structural differences even among structurally related compounds or compositions can result in substantially different biology, expression and activities.
Therefore, there is insufficient written description for genera of CAR molecules, as broadly encompassed by the claimed invention at the time the invention was made and as disclosed in the specification as filed under the written description provision of 35 USC 112, first paragraph.
Applicant has been reminded that Vas-Cath makes clear that the written description provision of 35 USC 112 is severable from its enablement provision. (See page 1115.)
Claims 20 and 21 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 methods of treating cancer, does not reasonably provide enablement for treating and/or preventing any given disease or for preventing cancer. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
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 CAR molecules as therapeutics, the art of record contains no description of methods of treating any disease other than cancer. In a paper published in 2015, Whilding et al (of record) provide an exhaustive review of the state of the art regarding CAR therapy, and detail the problems associated with using CARs even for well-developed methods of cancer therapy. There are no descriptions of using CAR molecules according to the instant claims, of CAR molecules that can prevent cancer, and no description of using established CAR molecules for treatment of any disease other than cancer. Therefore, the use of CAR molecules to treat the broadly claimed scope of diseases was unpredictable at the time of filing.
Amount of direction provided by the inventor and existence of working examples: The specification provides details for producing CAR molecules according the claims, including direction and generalities for customizing CARs such that they may be directed to a wide range of distinct antigens displayed on cancer cells. There are no working examples of the claimed methods, or in vivo results.
Thus, in order to make and use the invention as claimed, the skilled artisan would have to further develop CARs used in the claimed methods of therapy with specificity and efficacy for any known disease (e.g. dementia, diabetes, heart failure), which would involve development of novel antigen binding domains, activation domains, etc. (even if such a large number of diseases could each be linked to a specific antigen).
Nature of the invention and Breadth of the claims: The claims are directed to methods of treating and/or preventing a disease, with no limitation placed on the nature of the disease. Thus, the claimed methods encompass treating or preventing a broad, divergent genus of potential diseases. As such, it is incumbent upon the disclosure to set forth the manner and process of making CARs, and methods of using such for therapy, 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 preparing CAR molecules for cancer treatment is high, one would not be able to make and use CAR molecules for therapy in any other type of disease 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 an efficacious treatment of a disease other than cancer using CAR molecules similar to those recited. Likewise, all of the teachings in the instant application are specifically directed to the treatment of cancer. 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 embodiments of the claimed invention that are operative in diseases other than cancer 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.
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 1-12, 15-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 10,172,886. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are generic claims anticipated by the ‘886 claims, which recite the same CARs with specific ligation-off domains, nucleic acids encoding the CARs, and methods of treating cancer with the CARs.
Conclusion
No claim is allowed.
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/MICHAEL D BURKHART/Primary Examiner, Art Unit 1638