Examiner of Record
The Examiner of record has changed.
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 .
Priority
Acknowledgement is made of Applicant’s CON of 17484386 (abandoned) which is a CON of 16528925 (abandoned) which is a CON of 15562843 which claims priority to at least PCT Application PCT/US2016/025883 filed on 4/04/2016, and Applicant’s claim to Domestic Benefit of earliest provisional application 62/142986 filed on 4/03/2015.
The priority date of instant is therefore, 4/03/2015.
Election/Restrictions
Applicant’s election without traverse of Group I and SEQ ID NO:76 in the reply filed on 6/16/2025 was previously acknowledged. Applicants subsequently cancelled non-elected claims 56-57 making the restriction requirement moot. Since SEQ ID NO:76 is free of the prior art of record, Examiner has removed the requirement for a single species election and is hereby examining all species.
Examiner’s Comments
This action is in response to papers filed 13th Mar 2026, in which the independent claim 37 and dependent claim 52 were amended, no claims were canceled, and no new claims were added. All of the amendments have been thoroughly reviewed and entered.
Amendments have overcome previous objections and rejections. However, this application contains rejections directed to species not previously examined.
Rejections not reiterated here are withdrawn.
Status of Claims
Claims 37-55 are currently under consideration.
Information Disclosure Statement
The information disclosure statement filed 4/24/2024 lists some references in duplicate. For e.g., Cite No. 17 and 18 are the same. Applicant is requested to check the rest of the IDS of any other duplications. The information disclosure statement was previously placed in the application file.
New Specification Objection
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 - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above. Specifically, the name and size of sequence listing provided with the application does not match the name and size of sequence listing in the Incorporation by Reference paragraph. Instant specification contains an incorporation by reference statement which is defective because it recites the total size as 211 KB. Size should be specified in bytes.
Required response – Applicant must 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.
New Claim Rejections - 35 USC § 102
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) 37-42, 45-46, 51-55 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Butler et al (US20160145629) cited by applicant as citation 17 on IDS filed 4/24/24, and cited by Examiner on previous Non-Final Office Action.
Regarding SEQ ID NO: 58:
Butler et al have disclosed siRNA compounds targeting TMPRSS including siRNAs comprising SEQ ID NO: 1201. SEQ ID NO: 1201 is 21 nucleotides in length and the siRNA consists of nucleobases identical to instant SEQ ID NO: 58, see alignment below. Further, SEQ ID NO: 1201 is comprised of sequences that are identical to or complementary to the instant SEQ ID NO:1.
RESULT 40
US-14-947-025-1201
(NOTE: this sequence has 2 duplicates in the database searched.
See complete list at the end of this report)
Sequence 1201, US/14947025
Patent No. 9783806
GENERAL INFORMATION
APPLICANT: ALNYLAM PHARMACEUTICALS, INC.
TITLE OF INVENTION: TMPRSS6 IRNA COMPOSITIONS AND METHODS OF USE THEREOF
FILE REFERENCE: 121301-00703
CURRENT APPLICATION NUMBER: US/14/947,025
CURRENT FILING DATE: 2015-11-20
PRIOR APPLICATION NUMBER: PCT/US2014/039149
PRIOR FILING DATE: 2014-05-22
PRIOR APPLICATION NUMBER: 61/912,988
PRIOR FILING DATE: 2013-12-06
PRIOR APPLICATION NUMBER: 61/826,178
PRIOR FILING DATE: 2013-05-22
NUMBER OF SEQ ID NOS: 1382
SEQ ID NO 1201
LENGTH: 21
TYPE: DNA
ORGANISM: Artificial Sequence
FEATURE:
NAME/KEY: source
OTHER INFORMATION: /note="Description of Artificial Sequence: Synthetic
oligonucleotide"
FEATURE:
NAME/KEY: source
OTHER INFORMATION: /note="Description of Combined DNA/RNA Molecule: Synthetic
oligonucleotide"
SEQ ID NO:1201 on bottom, instant SEQ ID NO:58 on top
Query Match 95.0%; Score 19; Length 21;
Best Local Similarity 78.9%;
Matches 15; Conservative 4; Mismatches 0; Indels 0; Gaps 0;
Qy 1 TCCACTGGCCCTGGGTGCA 19
:||||:|||||:|||:|||
Db 1 UCCACUGGCCCUGGGUGCA 19
Butler et al have also disclosed that siRNA compounds of their invention can be made from two single stranded oligonucleotides to form a duplex and further that the compounds of their invention can be single stranded antisense compounds (paragraphs 7, 120, 125, and 196-198, for example). It has been disclosed modifications to internucleoside linkages, sugar moieties and bases (see paragraphs 8, 12, 37, 241, 245, 247, SEQ ID NO:1003, and compound AD63450.1 (Table 13), for example). It has been disclosed conjugates such as GalNAc (see paragraphs 38, 64, 97, 396, and 399-408, for example). It has also been disclosed pharmaceutical compounds utilizing PBS (see paragraphs 123 and 445, for example). While the entire reference is relevant and relied on, applicant is directed to paragraphs 7, 8, 12, 37, 38, 41-46, 55, 62, 66, 120, 123, 125, 133, 196-198, 232, 238, 245-247, 249, 373, 388, 396, 399-408, and 445, for example.
Thus, Butler anticipates instant claims 37-42, 45-46, and 51-55.
Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 37-55 is/are rejected under 35 U.S.C. 103 as being unpatentable over Butler et al (US20160145629) cited by applicant as citation 17 on IDS filed 4/24/24, and cited by Examiner on previous Non-Final Office Action.
Butler et al have also disclosed that siRNA compounds of their invention can be made from two single stranded oligonucleotides to form a duplex and further that the compounds of their invention can be single stranded antisense compounds (paragraphs 7, 120, 125, and 196-198, for example). It has been disclosed modifications to internucleoside linkages, sugar moieties and bases (see paragraphs 8, 12, 37, 241, 245, 247, SEQ ID NO:1201, and compound AD63450.1 (Table 13), for example). It has been disclosed conjugates such as GalNAc (see paragraphs 38, 64, 97, 396, and 399-408, for example). It has also been disclosed pharmaceutical compounds utilizing PBS (see paragraphs 123 and 445, for example).
Butler et al do not specifically disclose a compound of based on SEQ ID NO:1201 that contains bicyclic sugar moieties or gapmer motifs.
Butler et al have taught to make siRNA and antisense compounds targeting TMPRSS expression to treat diseases such as beta-thalassemia and hemochromatosis. SEQ ID NO:1201 as AD63450.1 as shown in Table 13 was not further tested but other similar sequences were tested and shown to be effective inhibitors of TMPRSS expression, providing a motivation to make oligomeric compounds comprising or based on SEQ ID NO:1201. Butler et al have taught the benefits of modifications recited in the claims and have taught that one in the art can utilize any of the well-known and established modifications known in the art and also to utilize ligands for the increased effectiveness of oligomer administration to cells and tissues (paragraphs 238, 247 and 399-408, for example). It would have been obvious to utilize any of the modifications recited in the claims including the gapmer motifs, bicyclic moieties, and 5-methylcytosine, recited in claims 43, 47, 48, 49 and 50 since these modifications were well known and routinely utilized in the art at the time the application was effectively filed. While the entire reference is relevant and relied on, applicant is directed to paragraphs 7, 8, 12, 37, 38, 41-46, 55, 62, 66, 120, 123, 125, 133, 196-198, 232, 238, 245-247, 249, 373, 388, 396, 399-408, and 445, for example.
Thus, Butler make obvious instant claims 37-55.
The invention as a whole would therefore have been prima facie obvious to one in the art at the time the application was effectively filed.
Claim 37-38 are rejected under 35 U.S.C. 103 as being unpatentable over Bumcrot et al (US20140194489) cited by applicant as citation 14 on IDS filed 4/24/24, and cited by Examiner on previous Non-Final Office Action in view of Singh et al(International Journal or Pharmacology Vol.7(3):294-315, 5/18/2011, cited by applicant NPL citation 158 on IDS filed 4/24/24).
Claim interpretation of claim 38: The reference TMPRSS6 sequence is disclosed in the spec. as sequences of any of SEQ ID NOs: 1-6. SEQ ID NO: 1 is 3212 nucleotides long. Thus, the claim requires the oligomeric compound to be 85% complementary to TMPRSS6.
Bumcrot et al have taught the inhibition of TMPRSS6 expression via RNAi compounds to treat the same conditions recited in the instant claims. Bumcrot et al have taught the same reasons for targeting this gene for the treatment of disease, for example. Bumcrot et al have also taught the effects of inhibiting TMPRSS6. While the entire reference is relied upon applicant is directed to paragraphs 15, 322, 338, 5, 50, 57, 88, 89, 319, 322, and the claims, for example. Bumcrot et al do not teach the use of antisense compounds per se, but have indeed taught the use of nucleic acid based inhibitors of TMPRSS6. One in the art would have known that other gene expression inhibitors such as antisense and ribozymes were available and known at the time of invention as options. One in the art would also have recognized that the recited modifications to antisense compounds were well known and established in the art at the time of invention.
Singh et al have provided in a review article, a description of the state of the art of antisense compounds in the treatment of disease where the use of antisense compounds, RNAi compounds, and ribozymes are all discussed.
It is further the position of the examiner that the modifications recited in the claims were well known and established and routinely use in the art at the time of invention.
Since the prior art has already taught the use of RNAi compounds targeting the same gene for treating the same conditions and diseases as recited in the claims and since it was known that antisense compounds can be used to inhibit a desired gene, one in the art would clearly have known that antisense compound could be substituted for RNAi compounds with a reasonable expectation that they would function to produce the same end, namely the inhibition of a targeted gene to treat various diseases and conditions.
The invention as a whole would therefore have been prima facie obvious to one in the art at the time the invention was made.
Allowable Subject Matter
SEQ ID NO:76 is free of the prior art of record.
Conclusion
No claims are allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SHABANA MEYERING, Ph.D. whose telephone number is (703)756-4603. The examiner can normally be reached M - F: 9am to 5pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ram Shukla can be reached at (571) 272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SHABANA S MEYERING/Examiner, Art Unit 1635
/SHABANA S MEYERING/Examiner, Art Unit 1635 /RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635
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