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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 6/3/26 has been entered.
Election/Restrictions
Claims 6, 9-12 and 14-16 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 7/22/25.
Anti18a and Anti19b in amended claim 1 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 7/22/25.
Response to Arguments
Applicant’s arguments, see pages 5-7, filed 5/28/26, with respect to the rejection(s) of claim(s) 1-4 under 103 based on Clarke (US20110021607) have been fully considered and are persuasive because of the amendment to claim 1. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of the amendment to the independent claim to require that the miRNA antisense inhibitor comprise ribonucleotides and deoxyribonucleotides, wherein said inhibitor is an anti200bc, anti429 or anti200a+141.
Drawings
Page 12 of the specification provides the following statement: The file of this patent contains at least one drawing executed in color. Copies of this patent with color drawings will be provided by the Patent and Trademark Office upon request and payment of the necessary fee.
However, there is no petition; one set of color drawings; or fee for color drawings of record. It appears that applicant did not intend file color drawings and the statement was a typographical error.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
Figure 4A has a nucleotide sequence. The Figure does not list the SEQ ID NO: for the sequence and the description for the drawing does not contain the corresponding SEQ ID NO:.
The sequence disclosures are located table 4 (SEQ ID NOs: 13-15). The sequence listing of record only contains 12 sequences.
Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
NOTE: in the response, please do not provide original claims or abstract since they are not required.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The claimed invention embraces a composition comprising antisense oligonucleotide that is complementary to miRNA selected from miR-200bc, miR-200a+141 or miR-429, wherein the oligonucleotide has at least two or more ribonucleotides and at least two or more deoxynucleotides and has at least two or more phosphorothioate linkers. The limitation “SERPINC1 miRNA antisense inhibitor” does not have patentable weight over the prior art teaching the structure of the claimed product because the limitation is a functional limitation that would be considered an inherent property of the claimed product. See MPEP 2112.01(I)-(II).
Claims 1-3 are rejected under 35 U.S.C. 103 as being unpatentable over Iba et al. (WO 2018169063, see English translation US Pre-grant publication 2020032262, which is a publication in English and the U.S. national application of ‘063). The pages cited in the following rejection will be from the ‘262 reference because the ‘063 publication is in Japanese.
‘262 discloses a composition comprising an miRNA inhibiting complex comprising an RNA or analog thereof comprising at least one double stranded structure and an miRNA binding sequence, wherein two strands of the binding sequence are each bound to one of two strands on at least one end of the double stranded structure (pages 1-9 and 61-63). A nucleic acid molecule comprising an miRNA binding sequence comprising the sequence of SEQ ID NO: 3 (wherein a uracil base is optionally a thymine base), and an miRNA binding sequence comprising the sequence of SEQ ID NO: 4 (wherein a uracil base is optionally a thymine base). SEQ ID NO: 4 comprises a sequence that is 100% identical to SEQ ID NO: 8. See pages 3 and 9 of ‘262, SEQ ID NO: 4 (Db). SEQ ID NO: 8 (Qy) is the sequence listed in the instant disclosure for claimed anti-200bc antisense inhibitor.
Qy 1 GGCAGTATTA 10
Db 8 GGCAGUAUUA 17
Pages 14-44 of ‘262 contemplate chemically modifying the miRNA binding sequence comprising a 2’-OMe modification, LNA modification and/or phosphorothioate linkages.
‘262 does not specifically teach that miRNA binding sequence comprising at least one phosphorothioate linkage.
It would have been prima facie obvious to a person of ordinary skill in the art before the time of the effective filing date to add phosphorothioate linkages to the miRNA binding sequence to increase the bioavailability of the sequence in a cell. When a person of ordinary skill in the art makes the miRNA binding sequence comprise thymine bases in place of uridine bases as set forth in pages 1-9 of ‘262, it would read on the sequence having a plurality of deoxyribonucleotides and ribonucleotides. In addition, it would have been obvious to one of ordinary skill in the art to further modify the miRNA binding sequence to comprise a 2’-OMe modification or a LNA modification to increase the bioavailability of the sequence in a cell.
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.
Claims 1-3 are rejected under 35 U.S.C. 103 as being unpatentable over Khvorova (US 20110263680).
’680 teaches making double stranded nucleic acid molecule comprising a guide strand (18-23 nucleotides in length) that is complementary to a microRNA and a passenger strand (8-16 nucleotides in length) that is identical to the microRNA. See pages 1-21, 26-30, and 69-158 and Tables 4-5. Two of the double stranded nucleic acid molecules target miR-200 and the passenger strand (sense strand) would read on a nucleic acid sequence for anti-200bc. See SEQ ID NO: 1739 (Db) and 1745 (DB) in table 4 that would read on SEQ ID NO: 8 which is sequence for an anti-200bc antisense inhibitor listed in the instant disclosure.
Qy 1 GGCAGTATTA 10
Db 5 GGCAGUAUUA 14
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745
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The sense strand for sd-rxRNA labeled MIMAT0000318 and MIMAT0000617 in table 5 would embrace the chemical modification limitations recited in the instant claims.
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158
791
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180
451
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The sense strand for the two nucleic acid molecules would read on the claimed product except for the limitation “conjugated by phosphorothioate linkers”.
It would have been prima facie obvious to a person of ordinary skill in the art before the time of the effective filing date to conjugate the nucleotides by phosphorothioate linkers to increase nuclease resistance to nuclease in a cell (pages 15-18). As set forth in table 5, the double stranded nucleic acid would contain a plurality of ribonucleotides and deoxyribonucleotides. It would have been obvious to one of ordinary skill in the art to make a composition comprising the double stranded nucleic acid molecule to assist in delivery of the molecule to cells. As shown in table 5, the molecule can have at least one 2’-OMe modification in the sense strand.
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over as applied to either Iba et al. (WO 2018169063) or Khvorova (US 20110263680), claims 1-3 above, and further in view of Manoharan (US 20120035115, of record).
Neither ‘063 nor ’680 specifically teach conjugating the nucleic acid molecule to a GalNAc conjugate.
However, Manoharan et al. teach a composition comprising an antagomir (also known as a miRNA antisense inhibitor) comprising phosphorothioate linkers and 2'-OMe modifications. A cholesterol moiety (GalNAc) can be conjugated at the 3' end of an oligonucleotide to target liver cells (Paragraphs 294, 600, 605, 644 and Tables 2 and 6).
It would have been prima facie obvious to a person of ordinary skill in the art before the time of the effective filing date to combine the teaching of either ‘063 or ‘680 taken with Manoharan et al. to attach a GalNAc conjugate to the 3' end of the nucleic acid molecule, namely to arrive at the claimed invention. There are only four options for attaching the moiety to the oligonucleotide (5' or 3' end of either passenger or guide strand). See MPEP 2143(I)E. One of ordinary skill in the art would have been motivated to combine the teaching to assists in the delivery of the oligonucleotide to ASGPR on liver cells.
Therefore the invention as a whole would have been prima facie obvious to one ordinary skill in the art before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains.
Conclusion
See attached PTO-326 for disposition of claims.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brian Whiteman whose telephone number is (571)272-0764. The examiner can normally be reached on Monday thru Friday; 6:00 AM to 3:00PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at (571)-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRIAN WHITEMAN/ Primary Examiner, Art Unit 1636
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