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 .
DETAILED ACTION
Request for Continued Examination
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 04/09/2026 has been entered.
Status of Application/Amendment/Claims
Applicant's response filed 04/09/2026 has been considered. Rejections and/or objections not reiterated from the previous office action mailed 10/09/2025 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
With entry of the amendment filed on 04/09/2026 claims 82-112 are pending and are currently under examination.
The 112(a) enablement rejection has been withdrawn in response to claim amendments.
Claims 86-100 and 106-112 are free of the prior art.
New Claim Rejections
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 82-84 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 pre-AIA the applicant regards as the invention.
Claims 82 and 84 are indefinite for the following reasons: the claim recites the nucleotides at any one or more of positions 2, 4, 5, 6, 8, 10, 12, 14, 16, and 20 from the 5' end of the antisense strand are not 2'-methoxy-ribonucleotides in (4) and the nucleotides at any one of more of positions 4, 6, 8, 10, and 14 from the 5' end of the sense strand are not 2'-methoxy-ribonucleotides in (9) and is indefinite because they recite some of the same positions. The claim is written such that the antisense has all of the conditions of 1-10 so in (4), position 4 is not a 2’-O-methyl modification and then it (9) this position is repeated. Condition (9) appears to limit (4) but this is improper within a claim and thus is indefinite.
The claims also recites in (5) the nucleotides at positions 1-2 to 1-7 from the 3' end of the antisense strand are connected to each other via phosphorothioate internucleotide linkages. It is unclear what is meant by 1-2 to 1-7. Is 1-2 or 1-7 intended to be in the alternative such that nucleotides at positions 1-2 or 1-7 from the 3’ end are connected to each other? Or does not mean any of positions 1-7 (which includes 1-2) are connected to each other?
The claims also recites in (6) a portion of the antisense strand is complementary to a portion of the sense strand and is indefinite because the metes and bounds of “portion” are not defined in the claims or specification. It is unclear how many nucleotides of the antisense strand is complementary to the sense strand. A portion could be considered as 2 complementary nucleotides or up to 14 of the 15 nucleotides of the sense strand.
Claim 83 is indefinite because it depends from claim 82.
Closet prior art and Allowable Subject Matter
The closest prior art for dsRNA targeted to SEQ ID No. 1 and SEQ ID No. 2 are taught by US20160319278 (see alignments below). The prior art teach dsRNA (siRNA) targeted to SEQ ID Nos. 1 and 2 but do not teach the claimed sequences or modifications a positions of modified nucleotides as in claims 82, 83, 85, 86, 97, 98 or Formulas I-IV, for example. A review of the sequence results do not reveal any sequence that comprises any of the claimed sequences with the specific modification patterns.
The instant specification describes SEQ ID Nos. 1 and 2 as target sites of Flt-1
The prior art does not teach using any of the claimed sequences in methods of treating or managing pre-eclampsia or Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP). Regarding modified claims 82 and 84, the prior art does not teach a dsRNA comprising the lengths and modifications in in methods of treating or managing pre-eclampsia or Hemolysis, Elevated Liver enzymes and Low Platelets (HELLP).
The gene sequence of Flt-1 is known as NC_000013.11 and methods of making siRNA sequences to a known target are known however, Sciabola et al. ("PFRED: A computational platform for siRNA and antisense oligonucleotides design." PLoS One 16.1 (2021)) teach designing antisense oligonucleotides can be logistically challenging given there are many design criteria that can be incorporated into the selection tool or therapeutic sequences and describes numerous different computational tools to address different aspects of the design process (page 2). Thus nothing in Sciabola et al. would lead one of skill in the art to a predictable computational tool to make it obvious to design sequences targeted to Flt-1 comprising the claimed structure and modifications.
SEQ ID No. 1
Sequence 324, US/15089423
Publication No. US20160319278A1
GENERAL INFORMATION
APPLICANT: UNIVERSITY OF MASSACHUSETTS
TITLE OF INVENTION: FULLY STABILIZED ASYMMETRIC SIRNA
FILE REFERENCE: 580035: UM9-209
CURRENT APPLICATION NUMBER: US/15/089,423
CURRENT FILING DATE: 2016-04-01
PRIOR APPLICATION NUMBER: 62/287,255
PRIOR FILING DATE: 2016-01-26
PRIOR APPLICATION NUMBER: 62/205,218
PRIOR FILING DATE: 2015-08-14
PRIOR APPLICATION NUMBER: 62/142,786
PRIOR FILING DATE: 2015-04-03
NUMBER OF SEQ ID NOS: 893
SEQ ID NO 324
LENGTH: 19
TYPE: DNA
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide
Query Match 95.0%; Score 19; Length 19;
Score over Length 100.0%;
Best Local Similarity 100.0%;
Matches 19; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 2 TCTCGGATCTCCAAATTTA 20
Db 19 TCTCGGATCTCCAAATTTA 1
SEQ ID No. 2
Sequence 232, US/15089423
Publication No. US20160319278A1
GENERAL INFORMATION
APPLICANT: UNIVERSITY OF MASSACHUSETTS
TITLE OF INVENTION: FULLY STABILIZED ASYMMETRIC SIRNA
FILE REFERENCE: 580035: UM9-209
CURRENT APPLICATION NUMBER: US/15/089,423
CURRENT FILING DATE: 2016-04-01
PRIOR APPLICATION NUMBER: 62/287,255
PRIOR FILING DATE: 2016-01-26
PRIOR APPLICATION NUMBER: 62/205,218
PRIOR FILING DATE: 2015-08-14
PRIOR APPLICATION NUMBER: 62/142,786
PRIOR FILING DATE: 2015-04-03
NUMBER OF SEQ ID NOS: 893
SEQ ID NO 232
LENGTH: 20
TYPE: DNA
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Description of Artificial Sequence: Synthetic oligonucleotide
Query Match 100.0%; Score 20; Length 20;
Score over Length 100.0%;
Best Local Similarity 100.0%;
Matches 20; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 CATCATAGCTACCATTTATT 20
Db 20 CATCATAGCTACCATTTATT 1
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kimberly Chong at (571)272-3111. The examiner can normally be reached Monday thru Friday between M-F 8:00am-4:30pm.
If attempts to reach the examiner by telephone are unsuccessful please contact the SPE for 1636 Neil Hammell at 571-272-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KIMBERLY CHONG/
Primary Examiner Art Unit 1636
Prosecution Insights