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 .
Claims 1-10 are pending in the application.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
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.
Claim 1 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a nature based product without significantly more. The claim(s) recite(s) a polypeptide selected from the group of a B-Gen.1 having a sequence at least 80% identical to SEQ ID NO: 1, a B-Gen.1 having a sequence at least 80% identical to SEQ ID NO: 39, and a B-Gen.2 having a sequence at least 80% identical to SEQ ID NO: 2, or a nucleic acid encoding said sequences. The specification discloses said sequences were identified from a genomic analysis of an in-house microbial databases (page 107, example 1, 1st paragraph). This judicial exception is not integrated into a practical application because the DNA sequences having SEQ ID NO: 1, 2 and 39 are from microbial databases that comprises naturally occurring microbial species. Whether the sequences are isolated from the microbial species or synthesized does not include additional elements from its nature based counterpart, which is a naturally occurring nucleic acid, and the polypeptide encoded by said nucleic acid sequence. Therefore, the claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because claim 1 does not recite any additional elements.
Claim 7 is rejected under 35 USC §101 because the claimed invention is directed to non-statutory subject matter. The term “cell” as defined by the specification at page 99 line 28-31 states that a human embryo is encompassed by the term “cell,” and the cell is present or intended to be present in a human being, said cell becoming integrated into the human being and therefore being an inseparable part of the human itself. The scope of the claim, therefore, encompasses a human being, which is non-statutory subject matter. It would be remedial to recite “an isolated cell.” See 1077 O.G. 24, April 21, 1987.
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 1-8, 10 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 a polypeptide comprising SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 39 and nucleic acid encoding said polypeptide, composition comprising said polypeptide, cell comprising said composition, and method of modifying a cell or in vitro using said composition, does not reasonably provide enablement for polypeptide having 80% and above identity with said sequences, and nucleic acid encoding said polypeptide, composition comprising said polypeptide, cell comprising said composition, and method of modifying a cell or in vitro using said composition. 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/use the invention commensurate in scope with these claims.
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 nature of the invention; (b) the breadth of the claims; (c) the state of the prior art; (d) the amount of direction provided by the inventor; (e) the existence of working examples; (f) the relative skill of those in the art; (g) whether the quantity of experimentation needed to make or use the invention based on the content of the disclosure is "undue"; and (h) the level of predictability in the art (MPEP 2164.01 (a)).
The nature of the invention
Claims 1-8, 10 are drawn to a polypeptide comprising 80% sequence identity with SEQ ID NO: 1, SEQ ID NO: 2, SEQ ID NO: 39 and nucleic acid encoding said polypeptide, composition comprising said polypeptide, cell comprising said composition, and method of modifying a cell or in vitro using said composition.
The breadth of the claim
The scope of the claim encompasses polypeptide comprising 80% sequence identity with SEQ ID NO: 1, 2, and 39.
The teaching from the specification and the presence of working examples
The specification teaches identification of novel type V CRISPR Cas nucleases named B-GEn.1, 1.2 and 2 from microbial databases (example 1). The specification teaches the screening assay identifies B-GEn.1, 1.2 and 2 encoded by SEQ ID NO: 1, 29 and 2 has nuclease activity with half of the designed sgRNA, SEQ ID NO: 40-44 in mammalian cells HEK 293T (Figure 2, and page 108, example 2). However, the specification does not teach any polypeptide (or nucleic acid encoding the polypeptide) having 80% and above sequence homology that has the nuclease activity in vitro or in a cell. Since the function of the polypeptide is directed to a type V RNA programmable endonuclease system that works in combination with sgRNAs, one of skilled in the art would not know how to use polypeptide(s) or nucleic acid encoding said polypeptide without nuclease function.
The teaching from prior art and the predictability in the art
Sequence search of SEQ ID NO: 1, 2 and 39 does not reveal any polypeptide sequence in prior art that has 80% and above identity with SEQ ID NO: 1, 2 and 39. Koonin et al. (IDS) teaches “the unifying feature of all type II and type V subtypes is the presence of a RuvC-like endonuclease domain that adopts the RNase H fold. However, the other parts of the Cas9 and Cas12 (type V) protein from different subtypes show no similarity to one another at the sequence or structure levels.” (page 71, 2nd col., last paragraph). In a more recent review article (Xuan et al., Int. J. Mol. Sci. 2024, Vol.25, 12686, pages 1-19), Xuan et al. teach that there are more than 10 subtypes of type V CRISPR-Cas have been identified, and these subtypes have different functional properties, depending on their structure, mechanism, and evolutionary development (page 3, Figure 2, and last paragraph). Due to the diversity in structure and function of the type V CRISPR system as discussed in prior art, whether sequences having homology with newly identified B-GEn type V nuclease has the nuclease function is unpredictable. Whether these polypeptides having sequence homology of 80% and above would have nuclease activity with single heterologous sgRNA, recognizing the same PAM sequence, and/or efficient targeting in combination with sgRNA having SEQ ID NO: 40-44 would have been unpredictable.
The amount of experimentation required
In view of the lack of teaching from the prior art and the present specification for polypeptides with sequence variation to SEQ ID NO: 1, 2, and 39, the ordinary skilled in the art would have to engage in undue experimentation to test a large number of different sequences, in combination with different sgRNA, and PAM sequences for their ability to perform DNA modification in vitro and in vivo. Therefore, the claimed invention is only enabled to the scope as indicated above.
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.
Claim 1-10 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 4, 5, 8, 9, 11, 15, 18, 20-22, 25, 27, 29-32 of copending Application No. 19525374 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because SEQ ID NO: 1 (claim 1 and 3) and SEQ ID NO: 4 (claim 5) of ‘374 application has 100% and 99.9% sequence identity with presently claimed SEQ ID NO: 1 claimed in claim 1 of present application. (alignment attached)
Dependent claims 2-10 are obvious in view of claims 4, 5, 8, 9, 11, 15, 18, 20-22, 25, 27, 29-32 of ‘374 application because claims from both application recites the polypeptide of claim 1 combined with guide RNA, a cell that comprises said combination, and method of modifying nucleic acid using said combination.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1-10 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-12, 16-20, 23, 25-29 of copending Application No. 19261,615 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because SEQ ID NO: 6 (claim 1) of ‘615 application has 100% sequence identity with presently claimed SEQ ID NO: 2 claimed in claim 1 of present application. (alignment attached)
Dependent claims 2-10 are obvious in view of claims 2-12, 16-20 and 25-29 of ‘615 application because claims from both application recites the polypeptide of claim 1 combined with guide RNA, a cell that comprises said combination, and method of modifying nucleic acid using said combination.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1-10 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-29 of copending Application No. 19/139,160 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because SEQ ID NO: 6 (claim 1) of ‘160 application has 100% sequence identity with presently claimed SEQ ID NO: 2 claimed in claim 1 of present application. (alignment attached)
Dependent claims 2-10 are obvious in view of claims 2-29 of ‘160 application because claims from both application recites the polypeptide of claim 1 combined with guide RNA, a cell that comprises said combination, and method of modifying nucleic acid using said combination.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
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/CELINE X QIAN/ Primary Examiner, Art Unit 1637
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