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 .
Applicant’s election without traverse of group I and the species receptor and DNA-binding protein in the reply filed on 1/21/26 is acknowledged.
Claims 6, 21, 22, and 24-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 1/21/26.
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 1-4 and 7-20 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims require for the dsDNA to comprise any effector sequence that encodes any effector. The specification does not adequately describe the structure required for the sequence to meet the instant limitation of being an effector sequence and having the function of encoding an effector.
The specification discloses: [0602] As used herein, the term “effector sequence” refers to the part of a DNA molecule that exerts a function on a cell, either directly (wherein the effector sequence is a functional DNA sequence) or by encoding a functional RNA or protein. The encoded functional RNA or protein is referred to as the “effector”.
The specification does not adequately describe the genus of the part of any DNA molecule that exerts any function on a cell. The specification discloses the species recited in instant claims 5 and 6, which is not representative of the entire claimed genus. Without further knowledge of the structure required for the function, one would not be able to readily recognize which sequences are necessarily included or excluded from the recited genus and would therefore not be able to readily recognize that applicant was in possession of the entire genus at the time of filing.
The MPEP states that for a generic claim, the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. See MPEP § 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP § 2163. Although the MPEP does not define what constitute a sufficient number of representative species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad genus. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618. Additionally, in Carnegie Mellon University v. Hoffman-La Roche Inc., Nos. 07-1266, -1267 (Fed. Cir. Sept. 8, 2008), the Federal Circuit affirmed that a claim to a genus described in functional terms was not supported by the specification’s disclosure of species that were not representative of the entire genus. Furthermore, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The claims are rejected under the written description requirement for failing to disclose adequate species to represent the claimed genus, the genus being double stranded RNAi agents of any length that comprise 15 contiguous nucleotides of instant SEQ ID NO: 669 in the antisense strand in the same or a different portion than the double-stranded region and have no other sequence specificity to any specific HAO1 target sequence and function by inhibiting the expression of HAO1.
The Guidelines for Examination of Patent Applications under the 35 USC § 112, first paragraph, “Written Description” Requirement”, published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole covers, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing.
Thus, having analyzed the claims with regard to the Written Description guidelines, it is clear that the specification does not disclose a representative number of species for effector sequences within the instant enormous genus that function as claimed. Thus, one skilled in the art would be led to conclude that Applicant was not in possession of the claimed invention at the time the application was filed.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 23 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Luhnsdorf et al. (Anal. Biochem. 425 (2012) 47–53).
Luhnsdorf et al. teach generation of reporter plasmids containing defined base modifications in the DNA strand of choice (title). Luhnsdorf et al. teach: The procedure exploits excision of a stretch of 18 nt from either the transcribed or nontranscribed DNA strand with the help of the sequence-specific nicking endonucleases Nb.Bpu10I and Nt.Bpu10I. The excised single-stranded oligonucleotide is then swapped for a synthetic DNA strand containing a desired base modification. Base modifications that form Watson–Crick-type base pairs were efficiently incorporated into plasmid DNA by a straightforward strand exchange, which was achieved by local melting in the presence of large excesses of the synthetic oligonucleotides and reannealing followed by ligation (abstract). The modifications are not 5-hydroxymethyluracil (page 50).
Therefore, the claim is anticipated by Luhnsdorf et al.
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 nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-5 and 7-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Luhnsdorf et al. (Anal. Biochem. 425 (2012) 47–53), in view of Bilyard et al. (Current Opinion in Chemical Biology 2020, 57:1–7), Benner et al. (US 10,865,431 B1), and Oliynyk et al. (COMMUNICATIONS BIOLOGY| (2022) 5:1393, 1-10).
Luhnsdorf et al. teach generation of reporter plasmids containing defined base modifications in the DNA strand of choice (title). Luhnsdorf et al. teach: The procedure exploits excision of a stretch of 18 nt from either the transcribed or nontranscribed DNA strand with the help of the sequence-specific nicking endonucleases Nb.Bpu10I and Nt.Bpu10I. The excised single-stranded oligonucleotide is then swapped for a synthetic DNA strand containing a desired base modification. Base modifications that form Watson–Crick-type base pairs were efficiently incorporated into plasmid DNA by a straightforward strand exchange, which was achieved by local melting in the presence of large excesses of the synthetic oligonucleotides and reannealing followed by ligation (abstract) (instant claims 1-3).
Luhnsdorf et al. teach that the plasmid has a protein coding strand (page 48), meeting the instant limitation of an effector sequence that encodes an effector (instant claim 1). The protein coding sequence codes for EGFP, which is a receptor (instant claim 5). The sequence encoding for EGFR is under the control of a CMV promoter (instant claim 4), wherein the plasmid is depicted in Figure 1 (instant claim 9).
Luhnsdorf et al. teach purification (page 52) (instant claim 18).
Luhnsdorf et al. is evidence that it was known to incorporate strand specific modifications into circular dsDNA plasmids (claim 1). However, Luhnsdorf et al. does not teach that at least 50% of the thymine or uracil positions in the first strand comprise 5-hydroxymethyuracil.
However, Bilyard et al. teach that 5-hydroxymethyuracil is an example of a modified DNA base (Figure 1). Bilyard et al. teach that the four canonical bases that make up genomic DNA are subject to a variety of chemical modifications in living systems (abstract). Bilyard et al. teach that modifications are known to increase mechanical stability (page 5). Given that DNA modifications were known to include 5-hydroxymethyuracil and to increase stability, it would have been obvious to incorporate 5-hydroxymethyuracilat varying percentages of nucleotide positions as a matter of design choice. The percentage would vary depending upon the sequence of the plasmid. It was known to incorporate chemical modifications into a single strand of circular dsDNA plasmids, as taught by Luhnsdorf et al. and 5-hydroxymethyuracil was a known DNA modification, as taught by Bilyard et al (instant claims 1, 7, 8, and 14).
It is noted that instant claims 16 and 17 recite outcomes that would necessarily flow from the recited structure. The instant claims are compound claims rather than method claims.
It would have been obvious to incorporate any modification that is known to benefit DNA. For example, Benner et al. tech incorporation of 2′-O-methyl and 2′,3′-dideoxynucleoside derivatives in DNA for higher thermostability (column 2 and claim 1) (instant claims 10-13 and 15). One would reasonably expect for the modifications to impart the stability known in the art into the plasmid of Luhnsdorf et al.
Additionally, it would have been obvious to incorporate a second sequence encoding a protein into the plasmid of Luhnsdorf et al. as a matter of design choice. Luhnsdorf et al. is evidence of protein coding plasmid sequences and the ability to integrate additional oligonucleotide sequences (instant claims 19 and 20).
For example, Oliynyk et al. teach a protocol that describes how to take a linear double-stranded DNA fragment and efficiently circularize and purify this DNA fragment with minimal hands-on time (abstract). The circular dsDNA comprises inserted sequences for production of a guide DNA sequence from a promoter (Figure 1).
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 1-5, 7-20, and 23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12, 22, 23, 25-29 of copending Application No. 19/250,908 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because claim 1 of application ‘908 are directed to pharmaceutical compositions comprising dsDNA molecules, wherein the dsDNA is circular, wherein at least 50% of thymine or uracil positions in the first strand of the dsDNA molecule comprise 5-hydroxymethyluracil, and the second strand is free of chemically modified nucleobases, which are structural requirements required by instant claim 1. Claim 5 of application ‘908 recites that the dsDNA molecule comprises a promoter and an effector sequence that encodes an effector, wherein instant claim 1 requires an effector sequence that encodes an effector. The claim sets are obvious variations of each other and combinations of the claims of application ‘908 anticipate the instant claims. The claims of application ‘908 are directed to overlapping structural requirements.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Amy R Hudson whose telephone number is (571)272-0755. The examiner can normally be reached M-F 8:00am-6:00pm.
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/AMY ROSE HUDSON/ Primary Examiner, Art Unit 1636