DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This Office action is in response to the communication filed 8-12-26.
Claims 1, 2, 5-12, 14-17, 19-24 are pending in the instant application.
Claims 19-24 have been withdrawn as being drawn to a non-elected species or invention..
Claims 1, 2, 5-12, 14-17 have been examined on their merits as set forth below.
Response to Arguments and Amendments
Any objections or rejections not repeated in this Office are hereby withdrawn.
Maintained Rejections/Rejections Necessitated by Amendments
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 2, 5-12, 14-17 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. The claims are vague for the following reason.
The claims are drawn to double-stranded nucleic acid molecules comprising a sense strand 23 to 30 nt long and an antisense strand 25 to 32 nt long, including a sequence complementary to the sense strand, which sense strand includes a chemically modified nucleotide at least one position selected from at the 4th, 5th, 7th, and 14th positions and a chemically unmodified nucleotide at the 1st position from the 5' end, or a chemically modified nucleotide at the 1st, 4th, 5th, 7th, and 14th positions from the 5' end, and which antisense strand includes a chemically modified nucleotide at positions complementary to nucleotides to at least one position selected from at the 2nd, 3ʳᵈ, 6th, 8th, and 10th to 13th positions from the 5' end of the sense strand, or which 7th position from a 5’ end of the sense strand, which chemically modified nucleotide includes a sugar moiety modified with at least one selected from the group consisting of 2'-O-methyl, 2'-methoxyethoxy, 2'- fluoro, 2'-allyl, 2'-O-[2-(methylamino)-2-oxoethyl], 4'-thio, 4'-CH2-O-2'-bridge, 4'-(CH₂)₂- O-2'-bridge, 2'-LNA, 2'-amino, and 2'-O-(N-methylcarbamate), or which sense strand includes a chemically unmodified nucleotide at least one position selected from the group consisting of the 2nd, 3rd, 6th, 8th to 13th, and 15th to 30th 36th from a 5' end antisense strand includes a chemically unmodified nucleotide at a position complementary to a nucleotide at least one position selected from the 1st, 4th, 5th, 7th, 9th, and 14th to 30th 36th from a 5' end of the sense strand, or which antisense strand includes a chemically unmodified nucleotide at a position complementary to a nucleotide at least one position selected from the 1st, 4th, 5th, 9th, and 14th to 30th 36th from a 5' end of the sense strand, which double-stranded nucleic acid molecule optionally further comprises a polynucleotide 1 to 30 nt long at the 3' end of the sense strand, and a polynucleotide 1 to 30 nt long at the 5' end of the antisense strand, wherein the polynucleotide extending from the 3' end of the sense strand and the polynucleotide extending from the 5' end of the antisense strand are not complementary to each other.
It is unclear which nucleotide(s) at which lengths and relative to the respective termini incorporate the modifications claimed. The claims recite a multitude of lengths and modifications related to the distances from the 5’ and 3’ termini, and therefore encompass a myriad of possible modifications. The metes and bounds of the claims cannot be determined.
Appropriate clarification is required.
The following is a quotation of the first paragraph of 35 U.S.C. 112(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, 2, 5-12, 14-17 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 for the reasons set forth in the Office action mailed 5-12-26, and for the reasons set forth below.
Applicant’s Arguments
Applicant argues the following:
It is respectfully submitted that Claims 1 and 17, as amended, closely track expressly described and experimentally exemplified structures and therefore satisfy this standard. Claim 1 is supported by the expressly disclosed and exemplified strand lengths and modification patterns. The Office expressed concern that the former ranges of 19-36 nucleotides for the sense strand and 21-38 nucleotides for the antisense strand, together with the former optional modification language, were broader than the working examples.
Claim 1 has now been narrowed to a sense strand 23-30 nucleotides long and an antisense strand 25-32 nucleotides long. The linear RNAs used in Examples 1-17 employ a 25-nucleotide sense strand and a 27-nucleotide antisense strand. Example 18 and Table 26 additionally and expressly disclose the two endpoint embodiments of a 23-nucleotide sense strand paired with a 25-nucleotide antisense strand and a 30-nucleotide sense strand paired with a 32-nucleotide antisense strand.
Claim 1 has also been narrowed from requiring a modification at merely "at least one" of several possible positions to the two site-specific patterns actually described and tested. In the first alternative, the sense strand has chemically modified nucleotides at the 4th, 5th, 7th, and 14th positions and a chemically unmodified nucleotide at the 1st position from its 5' end. This is the P(-1)P pattern expressly described in Example 14 and Table 20. In the second alternative, the sense strand has chemically modified nucleotides at the 1st, 4th, 5th, 7th, and 14th positions from its 5' end. This is the P(+1)P pattern expressly described in Example 5. In both alternatives, the antisense strand has chemically modified nucleotides at all eight positions complementary to the 2nd, 3rd, 6th, 8th, and 10th-13th positions from the 5' end of the sense strand. Figures 1 and 2 schematically illustrate these P(+1)P and P(-1)P patterns, respectively.
…Claim 17 is also fully supported. The instant specification states that the double-stranded nucleic acid molecule may further include a polynucleotide 1-30 nucleotides long at the 3' end of the sense strand and a polynucleotide at the 5' end of the antisense strand, and specifically states that the two extending polynucleotides may be noncomplementary, thereby forming a flanking-end dsRNA. Example 9 and Table 14 provide a working flanking-end construct in which a 27-nucleotide polynucleotide extends from the 3' end of the sense strand and a 25-nucleotide polynucleotide extends from the 5' end of the antisense strand, and Figure 14 demonstrates gene-silencing activity for that construct. The two extending polynucleotides are not complementary to each other has been incorporated into the claims and expressly described flanking-end architecture and the working embodiment of Example 9 rather than encompassing an undefined relationship between the two extensions.
Response to Applicant’s Arguments
Applicant is correct that examples have been provided as to Example 9 and Table 14 providing a working flanking-end construct in which a 27-nucleotide polynucleotide extends from the 3' end of the sense strand and a 25-nucleotide polynucleotide extends from the 5' end of the antisense strand, and Figure 14 demonstrates gene-silencing activity for that construct. the two extending polynucleotides are not complementary to each other. Applicant's arguments filed 8-12-26 have been fully considered but they are not fully persuasive.
The breadth of the claims:
The claims are drawn to double-stranded nucleic acid molecules comprising a sense strand 23 to 30 nt long and an antisense strand 25 to 32 nt long, including a sequence complementary to the sense strand, which sense strand includes a chemically modified nucleotide at least one position selected from at the 4th,
5th, 7th, and 14th positions and a chemically unmodified nucleotide at the 1st position from the 5' end, or a chemically modified nucleotide at the 1st, 4th, 5th, 7th, and 14th positions from the 5' end, and which antisense strand includes a chemically modified nucleotide at positions complementary to nucleotides to at least one position selected from at the 2nd, 3ʳᵈ, 6th, 8th, and 10th to 13th positions from the 5' end of the sense strand, or which 7th position from a 5’ end of the sense strand, which chemically modified nucleotide includes a sugar moiety modified with at least one selected from the group consisting of 2'-O-methyl, 2'-methoxyethoxy, 2'- fluoro, 2'-allyl, 2'-O-[2-(methylamino)-2-oxoethyl], 4'-thio, 4'-CH2-O-2'-bridge, 4'-(CH₂)₂- O-2'-bridge, 2'-LNA, 2'-amino, and 2'-O-(N-methylcarbamate), or which sense strand includes a chemically unmodified nucleotide at least one position selected from the group consisting of the 2nd, 3rd, 6th, 8th to 13th, and 15th to 30th 36th from a 5' end antisense strand includes a chemically unmodified nucleotide at a position complementary to a nucleotide at least one position selected from the 1st, 4th, 5th, 7th, 9th, and 14th to 30th 36th from a 5' end of the sense strand, or which antisense strand includes a chemically unmodified nucleotide at a position complementary to a nucleotide at least one position selected from the 1st, 4th, 5th, 9th, and 14th to 30th 36th from a 5' end of the sense strand, which double-stranded nucleic acid molecule optionally further comprises a polynucleotide 1 to 30 nt long at the 3' end of the sense strand, and a polynucleotide 1 to 30 nt long at the 5' end of the antisense strand, wherein the polynucleotide extending from the 3' end of the sense strand and the polynucleotide extending from the 5' end of the antisense strand are not complementary to each other.
The genus of modified double stranded molecules encompassing all of the lengths of the sense and antisense oligonucleotides, and the myriad of constellations of modifications claimed, is expansive.
Teachings in the specification:
As stated previously, the specification teaches various double stranded nucleic acid molecules with and without various modifications, listed in Tables 1-8. The specification, prior art and claims do not adequately describe the expansive genus of modified nucleic acids claimed, comprising double stranded nucleic acid molecules comprising the various lengths and all of the modifications applicable to all of the lengths of the antisense and sense strands claimed.
Contrary to Applicant’s assertions, the examples taught in the specification are not representative of the genus of modified double stranded nucleic acids claimed. The specification fails to provide a representative number of species, and does not indicate what distinguishing attributes are concisely shared by the members of this genus including the various lengths and/or the long extensions lacking complementarity and their respective modifications.
For the reasons stated above, the instant rejection for lacking adequate written description is properly maintained.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Certain papers related to this application may be submitted to Art Unit 1637 by facsimile transmission. The faxing of such papers must conform with the notices published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 C.F.R. ' 1.6(d)). The official fax telephone number for the Group is 571-273-8300. NOTE: If Applicant does submit a paper by fax, the original signed copy should be retained by applicant or applicant's representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED so as to avoid the processing of duplicate papers in the Office.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jane Zara whose telephone number is (571) 272-0765. The examiner’s office hours are generally Monday-Friday, 10:30am - 7pm. If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Jennifer Dunston, can be reached on (571)-272-2916. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (703) 308-0196.
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Jane Zara
9-21-26
/JANE J ZARA/Primary Examiner, Art Unit 1637
