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 Preliminary Amendment filed January 15, 2025.
Claims 4, 6, 11-15, 19-23, 25-29, 36, 39, 41, 51-54, 56-57 have been canceled. Claims 1-3, 5, 7, 8, 10, 16-18, 24, 30-34, 37, 38, 40, 42, 44, 47, 50, 55, 58 and 59 have been amended.
Claims 1-3, 5, 7-10, 16-18, 24, 30-35, 37, 38, 40, 42-50, 55, 58 and 59 are pending in the present application.
Claims 1-3, 5, 7-10, 16-18, 24, 30-35, 37, 38, 40, 42-50, 55, 58 and 59 have been examined on the merits as detailed below:
Information Disclosure Statement
Applicant’s information disclosure statement (IDS) filed March 22, 2024 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
It is noted that there are no Drawings associated with the present application.
Claim Rejections - 35 USC § 112 – fourth paragraph
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 35 U.S.C. 112 (pre-AIA ), fourth paragraph:
Subject to the [fifth paragraph of 35 U.S.C. 112 (pre-AIA )], 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.
Claims 2 and 17 are 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. 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.
Claim 2 fails to further limit the polynucleic acid molecule of claim 1 since the polynucleic acid molecule has been amended to recite, “the polynucleic acid molecule of claim 1, wherein the polynucleic acid molecule comprises a nucleic acid sequence that is at least 90% complementary to the nucleic acid sequence of at least one of SEQ ID NOs: 2-4, 9-11, 14, 18, 22,25,28,30,31,34-37,42,45,48-50”. Appropriate correction is required.
Claim 17 fails to further limit the polynucleic acid molecule of claim 16 since the polynucleic acid molecule has been amended to recite, “wherein the antisense strand comprises a nucleic acid sequence that is at least 90%, at least 95% identical to one of SEQ ID NOs: 102-104, 109-111, 114, 118, 122, 125, 128, 130, 131, 134-137, 142, 145, 148-150.” Appropriate correction is required.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 5, 7-10, 16-18, 24, 30-35, 37, 38, 40, 42-50 and 55 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US Publication 20050255487 A1 to Dharmacon Inc. (hereinafter, “Dharmacon”).
The claims are drawn to a polynucleic acid molecule that modulates expression of Xanthine dehydrogenase (XDH) gene, wherein the polynucleic acid molecule comprises a nucleic acid sequence that is at least 90% complementary to the nucleic acid sequence of at least one of SEQ ID NOs: 2-4, 9-11, 14, 18, 22, 25, 28, 30, 31, 34-37, 42, 45, 48-50. NOTE: The polynucleotides of the present invention are targeted to XDH (e.g., NCBI gene accession reference sequence number NM_000379.4; NM_000379.3; or NM_000379.2).
Dharmacon is relevant and relied upon in its entirety. Dharmacon teach compositions for selecting siRNA of improved functionality. Dharmacon teach a particular siRNA polynucleic acid molecule which comprises a nucleic acid sequence that is at least 90% complementary to SEQ ID NO:11 of the present invention. See Dharmacon, Sequence 2230949. Also, see the following sequence alignment:
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The siRNAs of the Dharmacon invention include duplexes of two separate strands, as well as single strands that can form hairpin structures comprising a duplex region. Therefore, the siRNA antisense strand will comprise a nucleic acid sequence that is at least 90% identical SEQ ID NO: 111 of the present invention.
Dharmacon teaches that the siRNA of their invention comprise at least one 2' -modified nucleoside, at least one modified internucleotide linkage, or at least one inverted abasic moiety.
Dharmacon teaches that the siRNA of their invention comprise nucleotide analogs including nucleotides with bases such as inosine, queuosine, xanthine, sugars such as 2′-methyl ribose, non-natural phosphodiester linkages such as methylphosphonates, phosphorothioates and peptides.
Dharmacon teaches that the siRNA of their invention comprise 90% to 100% chemical modification. See Figures 8a and 8b, for example.
Dharmacon teaches that the siRNA of their invention include, but are not limited to conjugations to other molecules, which may be used to facilitate delivery. In some embodiments, the siRNA are conjugated as siRNA-lipid complex formations.
Dharmacon teaches that the siRNA of their invention are applicable for use in silencing a broad range of genes associated with diseases such as diabetes, either in vivo or in vitro.
While Dharmacon does not explicitly teach that administration of the siRNA polynucleic acid molecule which comprises a nucleic acid sequence that is at least 90% complementary to SEQ ID NO:11 of the present invention inhibits XDH activity in a cell or treats a disorder associated with XDH, Dharmacon discloses the same method as claimed. Namely, administration of the siRNA polynucleic acid molecule that modulates expression of XDH gene in vivo or in vitro. Any underlying mechanism of action would naturally flow and be inherent to administration of the polynucleic acid molecule to the subject. See MPEP 2112 as it relates to inherency. Also, see In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990) and In re Best, 562 F.2d 1252 (CCPA 1977).
The Examiner has provided sound basis in fact and technical reasoning that reasonably supports the determination that the allegedly inherent characteristic necessarily flows from what has been specifically disclosed within the prior art and has shifted the burden to Applicant to provide evidence to the contrary.
Therefore, the subject matter of claims 1-3, 5, 7-10, 16-18, 24, 30-35, 37, 38, 40, 42-50 and 55 is anticipated by Dharmacon, absent some evidence to the contrary.
******
Claims 1-3, 5, 7-10, 16-18, 24, 30-35, 37, 38, 40, 42-50 and 55 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO 2021257782 A1 to ALNYLAM PHARM INC. (submitted and made of record on the IDS filed March 22, 2024).
ALNYLAM PHARM INC. is relevant and relied upon in its entirety. ALNYLAM PHARM INC. teach XANTHINE DEHYDROGENASE (XDH) iRNA COMPOSITIONS AND METHODS OF USE THEREOF. NOTE: The iRNA compositions of the ALNYLAM PHARM INC. invention are targeted to XDH (e.g., NCBI gene accession reference sequence number NM_000379).
ALNYLAM PHARM INC. teach a particular iRNA polynucleic acid molecule which comprises a nucleic acid sequence that is at least 90% complementary to SEQ ID NO:2 of the present invention. See ALNYLAM PHARM INC., Human XDH gene targeting siRNA sense strand, SEQ 45. Also, see the following sequence alignment:
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NOTE: ALNYLAM PHARM INC. also teach siRNA sense strand, SEQ 53, which comprises SEQ ID NO:3 of the present invention. NOTE: ALNYLAM PHARM INC. also teach siRNA sense strand, SEQ 250, which comprises SEQ ID NO:34 of the present invention. NOTE: ALNYLAM PHARM INC. also teach siRNA sense strand, SEQ 251, which comprises SEQ ID NO:35 of the present invention. NOTE: ALNYLAM PHARM INC. also teach siRNA sense strand, SEQ 254, which comprises SEQ ID NO:36 of the present invention. NOTE: ALNYLAM PHARM INC. also teach siRNA sense strand, SEQ 298, which comprises SEQ ID NO:42 of the present invention.
The iRNAs of the ALNYLAM PHARM INC. invention include duplexes of two separate strands, as well as single strands that can form hairpin structures comprising a duplex region. Therefore, the iRNA antisense strand will comprise a nucleic acid sequence that is at least 90% identical SEQ ID NO: 102 of the present invention.
ALNYLAM PHARM INC. teaches that the iRNA of their invention comprise at least one 2' -modified nucleoside, at least one modified internucleotide linkage, or at least one inverted abasic moiety.
ALNYLAM PHARM INC. teaches that the iRNA of their invention comprise nucleotide analogs including nucleotides with bases such as inosine, queuosine, xanthine, sugars such as 2′-methyl ribose, non-natural phosphodiester linkages such as methylphosphonates, phosphorothioates and peptides.
ALNYLAM PHARM INC. teaches that the iRNA of their invention may otherwise be completely modified.
ALNYLAM PHARM INC. teaches that the iRNA of their invention include, but are not limited to conjugations to other molecules, which may be used to facilitate delivery. In some embodiments, the siRNA are conjugated to cholesterol.
ALNYLAM PHARM INC. teaches that the iRNA of their invention are applicable for use for silencing a broad range of genes associated with diseases such as diabetes, either in vivo or in vitro. For example, ALNYLAM PHARM INC. teaches Xanthine Dehydrogenase dsRNA Agent in vitro Single Dose Screens in Primary Hepatocytes. See Tables 4, 5 and 8-12. ALNYLAM PHARM INC. also teaches the pharmacodynamic activity of siRNAs targeted to XDH in vivo. See Figures 2 and 3.
ALNYLAM PHARM INC. also teaches that the iRNA of their invention prevent or treat XDH-associated disease (preferably hyperuricemia and gout) in a subject.
Therefore, the subject matter of claims 1-3, 5, 7-10, 16-18, 24, 30-35, 37, 38, 40, 42-50 and 55 is anticipated by ALNYLAM PHARM INC., absent some evidence to the contrary.
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.
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 pre-AIA 35 U.S.C. 103(a) 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.
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.
Claims 58 and 59 are rejected under 35 U.S.C. 103 as being unpatentable over US Publication 20050255487 A1 to Dharmacon Inc. (hereinafter, “Dharmacon”) or WO 2021257782 A1 to ALNYLAM PHARM INC. (submitted and made of record on the IDS filed March 22, 2024) in view of Becker et al. (Diabetes, Obesity and Metabolism 15: 1049-1055, 2013).
The claims are as described above.
Dharmacon and ALNYLAM PHARM INC. are relied upon as described above.
Neither teach a method of treating a disorder associated with Xanthine dehydrogenase (XDH) activity in a subject comprising: a) providing a pharmaceutical composition comprising a polynucleic acid molecule that modulates expression of Xanthine dehydrogenase (XDH) gene, wherein the polynucleic acid molecule comprises a nucleic acid sequence that is at least 90% complementary to the nucleic acid sequence of at least one of SEQ ID NOs: 2-4, 9-11, 14, 18, 22, 25, 28, 30, 31, 34-37, 42, 45, 48-50; b) administering the pharmaceutical composition to the subject in a dose and schedule sufficient to modulate the XDH activity in the subject, thereby treating the disorder associated with XDH activity, and wherein the subject failed one or more first line standard of care therapies, including allopurinol or febuxostat treatment.
Becker et al. teach the efficacy and safety of febuxostat and allopurinol in patients with diabetes.
Before the effective filing date of the claimed invention, it would have been prima facie obvious for a person of ordinary skill in the art to devise a method of treating a disorder associated with Xanthine dehydrogenase (XDH) activity in a subject, such as diabetes comprising: a) providing a pharmaceutical composition comprising a polynucleic acid molecule that modulates expression of Xanthine dehydrogenase (XDH) gene, wherein the polynucleic acid molecule comprises a nucleic acid sequence that is at least 90% complementary to the nucleic acid sequence of at least one of SEQ ID NOs: 2-4, 9-11, 14, 18, 22, 25, 28, 30, 31, 34-37, 42, 45, 48-50; b) administering the pharmaceutical composition to the subject in a dose and schedule sufficient to modulate the XDH activity in the subject, thereby treating the diabetes disorder associated with XDH activity using the teachings and suggestions of Dharmacon or ALNYLAM PHARM INC.
A person of ordinary skill in the art would have been motivated to modify the teachings of Dharmacon or ALNYLAM PHARM INC. to include subjects who have failed febuxostat and allopurinol treatment prior to the siRNA treatment for the purpose of determining the therapeutic effect of the siRNA as a second line therapy.
A person of ordinary skill in the art would have expected reasonable success to devise the method as claimed by following the explicit disclosures and teachings of Dharmacon or ALNYLAM PHARM INC.
Therefore, the subject matter of claims 58 and 59 are obvious over Dharmacon or ALNYLAM PHARM INC. in view of Blecker et al.
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 1-3, 5, 7-10, 16-18, 24, 30-33, 40, 42 and 43 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
The claims are drawn to a polynucleic acid molecule that modulates expression of Xanthine dehydrogenase (XDH) gene, wherein the polynucleic acid molecule comprises a nucleic acid sequence that is at least 90% complementary to the nucleic acid sequence of at least one of SEQ ID NOs: 2-4, 9-11, 14, 18, 22, 25, 28, 30, 31, 34-37, 42, 45, 48-50. The present Specification discloses:
In some aspects, a polynucleic acid molecule comprises natural or synthetic or artificial nucleotide analogues or bases
The polynucleic acid molecule of the present invention comprise DNA and RNA nucleobases which are naturally occurring nucleic acids that are a product of nature. 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 do not require any type of chemical modification that would differentiate the polynucleic acid molecule 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 polynucleic acid molecules are a naturally occurring unmodified nucleic acid fragments.
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.
The polynucleic acid molecule of the claimed invention is a product of nature because it is a fragment of a naturally occurring 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.
Regarding claim 40, the polynucleic acid molecule can be conjugated to a carbohydrate which includes a naturally occurring substance such as cholesterol.
Regarding claim 42, the recitation of “A pharmaceutical composition comprising the polynucleic acid molecule of claim 1” 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 polynucleic acid molecules of the claimed invention are a product of nature because it is a fragment of a naturally occurring 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 cholesterol or water to the polynucleic acid molecules of the present invention does not make the nucleic acid patent eligible.
Thus, claims 1-3, 5, 7-10, 16-18, 24, 30-33, 40, 42 and 43 are not patent-eligible.
Conclusion
No claims are allowable at this time.
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.
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/TERRA C GIBBS/Primary Examiner, Art Unit 1635
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