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
Election/Restrictions
Applicant's election without traverse of Group I and SEQ ID Nos.255-259, 410 and SEQ ID 2 in the reply filed on 06/18/2026 is acknowledged.
Status of the Application
Claims 3-27 are pending. Claims 3-20 are currently under examination. Claims 21-27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
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 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.
Claim(s) 3-8, 11, 12, 19 and 20, is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Khvorova et al. (US Patent No. 8,090,542).
Regarding claims 3, 5 and 19, Khvorova et al. teach a double stranded oligonucleotide that consists of at least 14 contiguous nucleotides of SEQ ID No. 258 (see alignment below).
Regarding claims 4, the instant specification describes in Table 3 that SEQ ID No. 258 binds within 29,184-29,211 of SEQ ID No 2 and this meets the limitations of claim 4..
Regarding claim 6, the double stranded oligonucleotide of Khvorova et al. is at least 70% complimentary to SEQ ID No. 2.
Regarding claims 7, 8, 11 and 12, Khvorova et al. teach the oligonucleotide can comprise sugar modifications and 2’-OME modifications (see Fig. 8A and col. 12).
Regarding claim 20, Khvorova et al. teach a pharmaceutical composition (see 0184).
Patent No. 8090542
GENERAL INFORMATION
APPLICANT: Dharmacon, Inc.
APPLICANT: Khvorova, Anastasia
NUMBER OF SEQ ID NOS: 1591911
SEQ ID NO 1461603
LENGTH: 19
TYPE: DNA
ORGANISM: Homo sapiens
Query Match 87.0%; Score 17.4; Length 19;
Best Local Similarity 78.9%;
Matches 15; Conservative 3; Mismatches 1; Indels 0; Gaps 0;
SEQ 258 1 CATCATCACCACCACCATC 19
SEQ 1461603 1 CAUCAUCACCACCAUCAUC 19
Thus Khvorova et al. anticipates the instant claims.
Claim Rejections - 35 USC § 103
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 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 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 9, 10 and 13-18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Khvorova et al. (US Patent No. 8,090,542), Miyagishi et al. (Antisense and Nucleic Acid Drug Development, 2003, 13:1-7), Vickers et al. (The Journal of Biological Chemistry, 2003, 278:7108-7118, citation of record), Dean et al. (Oncogene, 2003, 22:9087-9096) and Grünweller et al. ("Comparison of different antisense strategies in mammalian cells using locked nucleic acids, 2′‐O‐methyl RNA, phosphorothioates and small interfering RNA." Nucleic acids research 31.12 (2003): 3185-3193).
Khvorova et al. is relied upon as above. Khvorova et al. do not teach the oligomeric compound is single-stranded and can be a gapmer comprising modified nucleotides such as bicyclic sugar moieties.
The prior art teach single stranded ASO and siRNA are functionally equivalent. Miyagishi et al. teach that ASO and siRNAs can be designed to be targeted to the same target sites with a reasonable expectation to observe reduced target expression levels with both molecules. (See siRNAs and antisense ASOs targeted to target sites 3, 4, 5, and 6 in Figure 1, wherein the ASO comprise all first 19 nucleotides of the antisense strand sequence of the siRNAs).
Vickers et al. teach, consistent with Miyagishi et al., that target sites between ASO and siRNAs are shared with reasonable correlation. See the entire reference.
Dean et al. corroborates the teachings of the Vickers et al. reference by stating that “As an example in comparing RNase H-dependent oligonucleotides to siRNA oligonucleotides, we found that they exhibited similar potency, duration of action, target selectivity and efficiency (Vickers et al., 2003).” (See page 9089, right column). Dean et al. also teach that one can incorporate LNAs into antisense oligonucleotides for increased target binding affinity and nuclease resistance. (See page 9090).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to substitute the siRNA of Khvorova et al. with a single stranded oligonucleotide because making both ASO compounds and siRNAs targeted to the same target sites of a gene was a known methodology in the art as taught by Miyagishi et al., Vickers et al., and Dean et al., and because substituting art-recognized equivalents known for the same purpose is a well-established rationale in support of an obviousness rejection. See MPEP 2144.06.
Grunweller et al. teach a comparison of different antisense strategies such as siRNA and LNA gapmers and found that both had high potency that makes them viable candidates for cell culture an in vivo applications (see abstract). Grunweller et al. teach the most promising modifications is locked nucleic acid (LNA), which contains a methylene bridge that connects the 2′‐oxygen of ribose with the 4′‐carbon and this 3′‐endo conformation leads to improved binding to complementary DNA and RNA sequences and increases the melting temperature (Tm) by several degrees. Grunweller et al. further teach chimeric LNA‐containing Ons, having a 8-10 DNA central region and 4-5 wings, have significantly higher serum stability, with up to 10‐fold increased half‐lives in human serum compared with unmodified AS oligodeoxynucleotides (ODNs). Furthermore, it was shown that chimeric LNA–DNA ONs with a central DNA stretch of 7–8 monomers activate RNase H (see page 3185 sec col).
It would have been obvious for one of ordinary skill in the art to make and use a single-stranded oligonucleotide, such as a LNA gapmer, to inhibit gene expression given it has been found that they can have higher serum stability and activate RNase H as taught by Grunweller et al.
Thus in the absence of evidence to the contrary, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 6 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 6 recites the oligonucleotide is complementary to “the nucleobase sequence of SEQ ID No. 1 or SEQ ID No. 2 and depends from claim 4 which recites only SEQ ID No. 2. Thus claim 6 broadens the scope of claim 4 and thus fails to further limit the claim.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Patent applicants with problems or questions regarding electronic images that can be viewed in the Patent Application Information Retrieval system (PAIR) can now contact the USPTO’s Patent Electronic Business Center (Patent EBC) for assistance. Representatives are available to answer your questions daily from 6 am to midnight (EST). The toll free number is (866) 217-9197. When calling please have your application serial or patent number, the type of document you are having an image problem with, the number of pages and the specific nature of the problem. The Patent Electronic Business Center will notify applicants of the resolution of the problem within 5-7 business days. Applicants can also check PAIR to confirm that the problem has been corrected. The USPTO’s Patent Electronic Business Center is a complete service center supporting all patent business on the Internet. The USPTO’s PAIR system provides Internet-based access to patent application status and history information. It also enables applicants to view the scanned images of their own application file folder(s) as well as general patent information available to the public. For more information about the PAIR system, see http://pair-direct.uspto.gov.
For all other customer support, please call the USPTO Call Center (UCC) at 800-786-9199.
/KIMBERLY CHONG/
Primary Examiner Art Unit 1636
Prosecution Insights