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
This Office Action is a response to Applicant’s Election filed July 24, 2025.
Claims 80, 88, 93, 95 and 96 have been canceled. New claims 98-101 are acknowledged. Claims 1, 4, 5, 13, 15, 16, 20, 23, 31, 34, 44, 52-55, 71, 73, 75, 76 and 78 have been amended.
Claims 1, 4, 5, 13, 15, 16, 20, 23, 31, 34, 44, 52-55, 71, 73, 75, 76, 78 and 98-101 are pending in the instant application.
Election/Restrictions
Applicant’s election (without traverse) of Group I in the reply filed on July 24, 2025 is acknowledged. Applicant’s species election of the nucleotide sequence 5'- UGAUUACUCAUUCAUUCGAUA-3' of SEQ ID NO: 96 as the species of sense strand sequence and the nucleotide sequence 5'-UAUCGAAUGAAUGAGUAAUCAUU-3' of SEQ ID NO:278 as the species of antisense strand sequence (e.g., duplex AD-1230934 in Table 2) in the reply filed on July 24, 2025 is also acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Accordingly, claims 1, 4, 5, 13, 15, 16, 20, 23, 31, 34, 44, 52-55, 71, 73, 75, 76, 78 and 98-101 have been examined on the merits as detailed below:
Information Disclosure Statement
Applicant’s information disclosure statement (IDS) filed July 24, 2025 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Drawings
The Drawings filed September 30, 2022 are acknowledged and have been accepted by the Examiner.
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.
Claim 54 is 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.
The term, “optional” in claim 54 renders the claims indefinite because it is unclear whether parts following the term, “optional” are actually a part of the claim. The term, “optional” is ambiguous and confusing since the alternatives covered by the claim are not clear. See MPEP 2173.05(h) for further explanation.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1, 4, 5, 23, 31, 34, 44, 52-55, 71, 73, 76 and 98-101 are rejected under 35 U.S.C. 101.
The claims are drawn to a double stranded ribonucleic acid (dsRNA) agent, or a salt thereof, for inhibiting expression of angiotensin converting enzyme 2 (ACE2) in a cell, wherein the dsRNA agent, or a salt thereof, comprises a sense strand and an antisense strand forming a double stranded region, wherein the antisense strand comprises a nucleotide sequence comprising at least 15 contiguous nucleotides of the nucleotide sequence 5’-UAUCGAAUGAAUGAGUAAUCAUU-3’ of SEQ ID NO:278; and wherein the sense strand or the antisense strand is conjugated to one or more lipophilic moieties. The present Specification teaches that a miRNA is a dsRNA and a lipophilic moiety is, for example, cholesterol. It should be noted that both miRNA and cholesterol are naturally occurring molecules.
The claimed invention is directed to a naturally-occurring nucleic acid fragment thereof, whether isolated or not that is not patent-eligible pursuant to the Supreme Court decision in Association for Molecular Pathology v. Myriad Genetics, Inc. -- U.S.-- (June 13, 2013). The claims read on naturally occurring nucleic acids that are a product of nature. The claims do not require any type of chemical modification that would differentiate the compound from a product of nature.
The fragments as claimed do not have to be shown to exist in nature, but only be shown to be a fragment of a naturally occurring gene. The Myriad decision clearly includes naturally-occurring nucleic acid fragments, whether isolated or not, and the claimed oligonucleotide is a naturally occurring unmodified nucleic acid fragment.
The logic in the Myriad decision was that snipping a nucleic acid out of the chromosome which contains it does not change it enough to make it eligible under 35 USC 101. That same logic applies whether it is a nucleic acid encoding a full-length protein or a part of the nucleic acid; either way it is a nucleic acid whose sequence is identical to what occurs in nature.
Also, it should be noted that cholesterol contains a significant aliphatic side chain (instant claim 52); and cholesterol comprising a saturated or unsaturated C4-C30 hydrocarbon chain constitutes naturally occurring fatty acids (present claims 54 and 55).
Further, recitation of “A pharmaceutical composition” (instant claim 76) is not enough to make the claim patent eligible. There is no limiting definition in the specification of what constitutes a pharmaceutical composition. The broadest reasonable interpretation of this term includes water. If the nucleic acid itself is not patent eligible, the addition of water does not make the nucleic acid patent eligible.
The dsRNA agent of the claimed invention is a product of nature because it is a fragment of a naturally occuring sequence and the fragment sequence is not markedly different than that found in nature. That is, the sequence is not modified or structurally different than the natural sequence. Furthermore, adding the natural product of cholesterol to the dsRNA agent of the present invention does not make the nucleic acid patent eligible.
Thus, claims 1, 4, 5, 23, 31, 34, 44, 52-55, 71, 73, 76 and 98-101 are not patent-eligible.
Conclusion
Claims 13, 15, 16, 20, 75 and 78 are objected to as being dependent upon a rejected base claim but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Art not relied upon
The following is art pertinent to Applicant’s disclosure but not relied upon: U.S. Patent No. 6821724 B1. The Patent teaches an array useful in gene expression analysis and for identifying polymorphisms and biallelic markers, comprising nucleic acid probes. U.S. Patent No. 6821724 teach a particular gene-specific probe which comprises SEQ ID NO: 96 of the present invention. See U.S. Patent No. 6821724, Sequence 73470. Also, see sequence alignment below:
PNG
media_image1.png
130
566
media_image1.png
Greyscale
The Patent does not teach or suggest a double stranded ribonucleic acid (dsRNA) agent, or a salt thereof, for inhibiting expression of angiotensin converting enzyme 2 (ACE2) in a cell, wherein the dsRNA agent, or a salt thereof, comprises a sense strand and an antisense strand forming a double stranded region, wherein the antisense strand comprises a nucleotide sequence comprising at least 15 contiguous nucleotides of the nucleotide sequence 5’-UAUCGAAUGAAUGAGUAAUCAUU-3’ of SEQ ID NO:278; and wherein the sense strand or the antisense strand is conjugated to one or more lipophilic moieties as presently claimed.
******
The following is also art pertinent to Applicant’s disclosure but not relied upon: U.S. Patent No. 12077758 B2. The Patent teaches and discloses novel angiotensin converting enzyme 2 (ACE2) targeting oligonucleotides. The targeting oligonucleotides are oligonucleotide compounds comprising 15 to 35 bases in length, comprising a sequence substantially complementary to an ACE2 nucleic acid sequence of any one of the 45-nucleotide target gene regions in Table 11D or Table 12C. The targeting oligonucleotides can be conjugated to a variety of targeting agents, including cholesterol.
U.S. Patent No. 12077758 teach a particular 45 nucleotide gene target region which comprises the nucleotide sequence of SEQ ID NO: 96 of the present invention. See U.S. Patent No. 12077758, Table 11D @SEQ ID NO: 2253. Also, see sequence alignment below:
PNG
media_image2.png
104
568
media_image2.png
Greyscale
U.S. Patent No. 12077758 B2 claims priority to Provisional Application 63084817, filed 09/29/2020 and Provisional Application 63031222, filed 05/28/2020.
The present application claims priority to Provisional Application 63125023, filed 12/14/2020; Provisional Application 63050135, filed 07/10/2020; and Provisional Application 63006383, filed 04/07/2020.
Therefore, U.S. Patent No. 12077758 B2 cannot be considered as prior art against the instant claims.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Terra C. Gibbs whose telephone number is 571-272-0758. The Examiner can normally be reached from 8 am - 5 pm M-F.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Ram Shukla can be reached on 571-272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free)? If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
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 all other customer support, please call the USPTO Call Center (UCC) at 800-786-9199.
/TERRA C GIBBS/Primary Examiner, Art Unit 1635