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 .
Applicant’s amendment filed on 10/17/2025 has been entered.
Amended claims 1, 3-11 and 17-19 are pending in the present application.
Applicant elected previously the following species without traverse: (i) a tetravalent branched structure; and (ii) a conjugated nucleic acid having the first structure recited in claim 7.
Accordingly, amended claims 1, 3-11 and 17-19 are examined on the merits herein with the above elected species.
Terminal Disclaimer
The terminal disclaimer filed on 10/17/2025 disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of US Patent No. 11174483, 11015198, or 11414660 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Response to Amendment
1. The rejection under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, for Lack of Written Description is withdrawn in light of currently amended claim 5, particularly with the deletion of the limitation “or derivatives thereof”.
2. All non-statutory double patenting rejections over claims of US Patent Nos. 11174483, 11015198 and 11414660 are withdrawn in light of the Terminal Disclaimer filed on 10/17/2025.
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.
Amended claims 1, 4, 11 and 17 are still rejected under 35 U.S.C. 102(a)(1) as being anticipated by Khvorova et al (US 7,691,997; IDS) for the same reasons set forth in the Office Action dated 06/18/2025 (pages 5-7). The same rejection is restated below.
The instant claims are drawn to a nucleic acid for inhibiting expression of a TMPRSS6 gene comprising at least one duplex region that comprises (i) at least a portion of a first strand, and (ii) at least a portion of a second strand that is at least partially complementary to the first strand, wherein the first strand is at least partially complementary to at least a portion of RNA transcribed from the TMPRSS6 gene, and wherein the first strand of said nucleic acid consists of the sequence of SEQ ID NO: 333, and wherein one or more nucleotides on the first strand are modified nucleotides, or one or more nucleotides on the second strand are modified nucleotides, or one or more nucleotides on the first strand and one or more nucleotides on the second strand are modified nucleotides.
Khvoraova et al already disclosed the 19-basepair siRNA of SEQ ID NO: 1480590, which antisense strand is 100% identical to the sequence of SEQ ID NO: 333 of the present application (see at least Abstract; col. 1, lines 26-31; col. 29, last paragraph continues to second paragraph at col. 30; Example VII; SEQ ID NO: 1480590 in the paper copy of the sequence listing of the submitted CD-ROM; and attached sequence searches below). In Example VII showing genome-wide applications of the algorithm, Khvoraova et al stated “To accomplish this for the human genome, the entire online ncbi refseq database was accessed through Entrez (efetch). The database was processed through Formula VIII. For each gene the top 80-100 scores for siRNAs were obtained and BLAST’ed to insure that the selected sequences are specific in targeting the gene of choice. These sequences are provided on the enclosed CDs in electronic form” (col. 53, last full paragraph). Khvoraova et al also disclosed that the term “siRNA” refers to small inhibitory RNA duplexes that induce the RNA interference (RNAi) pathway, and these molecules can vary in length (generally between 18-30 base-pairs) and contain varying degrees of complementarity to their target mRNA in the antisense strand; and that the term includes duplexes of two separate strands, as well as single strands that can form hairpin structures comprising a duplex region (col. 9, lines 14-24). Khvoraova et al also taught that siRNAs include siRNAs that contain substituted nucleotides, with the most common substitutions are at the 2’ position of the ribose sugar, wherein moieties such as H (hydrogen), F, NH3, OCH3, and other O-alkyl, alkenyl, alkynyl, and orthoesters, sulfur, amines or hydrocarbons may be substituted for the bridging of non-bridging atoms in the phosphodiester bond (col. 31, lines 32-40). Khvoraova et al also stated “The present invention is directed to improving the efficiency of gene silencing by siRNA. Through the inclusion of multiple siRNA sequences that are targeted to a particular gene and/or selecting an siRNA sequence based on certain defined criteria, improved efficiency may be achieved” (col. 13, lines 23-27); and “An siRNA selected according to this method may be used individually, or in conjunction with the first embodiment, i.e., with one or more other siRNAs, each of which may or may not be selected by this criteria in order to maximize their efficiency” (col. 13, lines 44-48). Khvoraova et al also taught that the siRNAs can be used with lipid-based carriers, cationic carriers, or simply formulating in a physiological acceptable solution (or physiological acceptable excipient) for applying to a cell in vitro or in vivo (col. 32, line 53 continues to line 7 on col. 33); and moieties such as specific conjugates or ligands (e.g., antibodies, antigens) can be added to the siRNA to facilitate its uptake (col. 34, line 57 continues to line 4 on col. 35).
Since the 19-basepair siRNA of SEQ ID NO: 1480590 of Khvoraova et al is identical in structure to the claimed nucleic acid of the present application, the reference anticipates the instant claims.
Response to Argument
Applicant’s arguments related to the above 102(a)(1) rejection in the Amendment filed on 10/17/2025 (pages 14-16) have been fully considered, however, they are respectfully not found persuasive for the following reasons.
Applicant argued that the sequence alignment on page 21 of the non-final Office Action dated 06/18/2025 showed that SEQ ID NO: 1480590 (provided in the Sequence Listing) has 100% match to SEQ ID NO: 18 of the present application, but there is no indication in the sequence listing of Khvorova of whether SEQ ID NO: 1480590 is an antisense sequence or a sense sequence, much less any reference of SEQ ID NO: 1480590 can be found in the specification of Khvorova. Applicant also argued that SEQ ID NO: 1480590 of Khvorova differs considerably from SEQ ID NO: 333 as recited in amended claim 1, and the mere disclosure of a sense strand does not disclose a corresponding anti-sense strand consisting of the 19 base pair sequence of SEQ ID NO: 333. Applicant further argued that the top sequence alignment on page 21 of the non-final Office Action dated 06/18/2025 provides a different sequence allegedly also depicted representing SEQ ID NO: 1480590, aligned to SEQ ID NO: 333 of the present application; and the querry sequence in the top alignment is not disclosed anywhere else in Khvorova. Since Khvorova is completely silent about the sequence used in the top alignment, Khorova does not disclose the nucleic acid of currently amended independent claim 1. Applicant also submitted that different sequences within a single patent application cannot both have the same SEQ ID NO.
First, the Khvorova reference discloses only a single SEQ ID NO: 1480590 with the 19-basepair sequence 5’-ucaccugcuucuucugguu-3’ that is 100% identical to the second strand of the nucleic acid for inhibiting expression of a TMPRSS6 gene in currently amended claim 1 (Abstract; col. 1, lines 26-31; and the paper sequence listing of the submitted CD-ROM). Khvorova et al also stated clearly “Incorporated by reference of sequence listing submitted on compact disc” (col. 1, lines 21-23); and “To accomplish this for the human genome, the entire online ncbi refseq database was accessed through Entrez (efetch). The database was processed through Formula VIII. For each gene the top 80-100 scores for siRNAs were obtained and BLAST’ed to insure that the selected sequences are specific in targeting the gene of choice. These sequences are provided on the enclosed CDs in electronic form” (col. 53, last full paragraph); coupled with the definition of the term “siRNA” referring to small inhibitory RNA duplexes that induce the RNA interference (RNAi) pathway, and these molecules can vary in length (generally between 18-30 base-pairs) and contain varying degrees of complementarity to their target mRNA in the antisense strand; and that the term includes duplexes of two separate strands, as well as single strands that can form hairpin structures comprising a duplex region (col. 9, lines 14-24); an ordinary skill in the art would readily recognize that the Khvorova reference discloses a selected siRNA comprising the 19-basepair strand with the sequence of 5’-ucaccugcuucuucugguu-3’ (SEQ ID NO: 1480590) and its corresponding 19-basepair complementary strand would have the sequence of 5’-aaccagaagaagcagguga-3’ that is 100% identical to the first strand with SEQ ID NO: 333 of the present application. This is supported by the sequence search for the first strand of SEQ ID NO: 333 of the present application that results in the target gene sequence for the siRNA strand with SEQ ID NO: 1480590 disclosed in the Khvorova reference as shown below.
Qy 1 AACCAGAAGAAGCAGGUGA 19
||||||||||||||||:||
Db 19 AACCAGAAGAAGCAGGTGA 1
Moreover, Khvorova et al also stated “It should be noted that in certain sequences, “t” is present. This is because many databases contain information in this manner. However, the “t” denotes a uracil residue in mRNA and siRNA” (col. 22, lines 35-38).
Second, please note that the incorporated by reference of sequence listing submitted on compact disc is part of the specification of the Khvorova reference. Khvorova et al also taught that siRNAs include siRNAs that contain substituted nucleotides, with the most common substitutions are at the 2’ position of the ribose sugar, wherein moieties such as H (hydrogen), F, NH3, OCH3, and other O-alkyl, alkenyl, alkynyl, and orthoesters, sulfur, amines or hydrocarbons may be substituted for the bridging of non-bridging atoms in the phosphodiester bond (col. 31, lines 32-40). Accordingly, the teachings of the Khvorova reference meet every limitation of the instant claims.
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.
Amended claims 1, 4-6, 8 and 18-19 are rejected under 35 U.S.C. 103 as being obvious over Khvorova et al (US 7,691,997; IDS) in view of Butler et al (US 10,829,763) for the same reasons set forth in the Office Action dated 06/18/2025 (pages 7-10). The same rejection is restated below.
Khvoraova et al already disclosed the 19-basepair siRNA of SEQ ID NO: 1480590, which antisense strand is 100% identical to the sequence of SEQ ID NO: 333 of the present application (see at least Abstract; col. 1, lines 26-31; col. 29, last paragraph continues to second paragraph at col. 30; Example VII; SEQ ID NO: 1480590 in the paper copy of the sequence listing of the submitted CD-ROM; and attached sequence searches below). In Example VII showing genome-wide applications of the algorithm, Khvoraova et al stated “To accomplish this for the human genome, the entire online ncbi refseq database was accessed through Entrez (efetch). The database was processed through Formula VIII. For each gene the top 80-100 scores for siRNAs were obtained and BLAST’ed to insure that the selected sequences are specific in targeting the gene of choice. These sequences are provided on the enclosed CDs in electronic form” (col. 53, last full paragraph). Khvoraova et al also disclosed that the term “siRNA” refers to small inhibitory RNA duplexes that induce the RNA interference (RNAi) pathway, and these molecules can vary in length (generally between 18-30 base-pairs) and contain varying degrees of complementarity to their target mRNA in the antisense strand; and that the term includes duplexes of two separate strands, as well as single strands that can form hairpin structures comprising a duplex region (col. 9, lines 14-24). Khvoraova et al also taught that siRNAs include siRNAs that contain substituted nucleotides, with the most common substitutions are at the 2’ position of the ribose sugar, wherein moieties such as H (hydrogen), F, NH3, OCH3, and other O-alkyl, alkenyl, alkynyl, and orthoesters, sulfur, amines or hydrocarbons may be substituted for the bridging of non-bridging atoms in the phosphodiester bond (col. 31, lines 32-40). Khvoraova et al also stated “The present invention is directed to improving the efficiency of gene silencing by siRNA. Through the inclusion of multiple siRNA sequences that are targeted to a particular gene and/or selecting an siRNA sequence based on certain defined criteria, improved efficiency may be achieved” (col. 13, lines 23-27); and “An siRNA selected according to this method may be used individually, or in conjunction with the first embodiment, i.e., with one or more other siRNAs, each of which may or may not be selected by this criteria in order to maximize their efficiency” (col. 13, lines 44-48). Khvoraova et al also taught that the siRNAs can be used with lipid-based carriers, cationic carriers, or simply formulating in a physiological acceptable solution (or physiological acceptable excipient) for applying to a cell in vitro or in vivo (col. 32, line 53 continues to line 7 on col. 33); and moieties such as specific conjugates or ligands (e.g., antibodies, antigens) can be added to the siRNA to facilitate its uptake (col. 34, line 57 continues to line 4 on col. 35). The 19-basepair siRNA of SEQ ID NO: 1480590 of Khvoraova et al is identical in structure to the claimed nucleic acid of the present application.
Khvoraova et al did not teach specifically at least that the siRNA is conjugated to a ligand comprising (i) one or more GalNac moieties, and (ii) a linker, wherein the linker has a bivalent or trivalent branched structure that conjugates the one or more GalNAc moieties to the siRNA.
Before the effective filing date of the present application (04/05/2017), Butler et al already disclosed double-stranded RNAi agents targeting TMPRSS6, and wherein the RNAi agents are conjugated to a ligand (e.g., one or more GalNac moieties attached via a bivalent or a trivalent branched linker) for at least enhanced targeting to a targeted cell or tissue (see at least Abstract; Summary of the Invention; particularly col. 20, last paragraph continues to second last paragraph on col. 23). Butler et al also taught that the ligand can be attached to the sense strand, antisense strand (second strand of the present application), or both strands, at the 3’-end, 5’-end, or both ends (col. 20, last paragraph). Butler et al stated explicitly “Ligands can improve transport, hybridization, and specificity properties and may also improve nuclease resistance of the resultant natural or modified oligoribonucleotide, or a polymeric molecule comprising any combination of monomers described herein and/or natural or modified ribonucleotides” (col. 23, second paragraph). Butler et al further disclosed that RNAi agents have modified backbones such as those contain phosphothioates or phosphorodithioates (col. 16, last paragraph continues to second paragraph at col. 17).
Accordingly, it would have been obvious for an ordinary skilled artisan before the effective filing date of the present application to modify the teachings of Khvoraova et al by also at least conjugating the siRNA with a ligand comprising (i) one or more GalNac moieties, and (ii) a linker, wherein the linker has a bivalent or trivalent branched structure that conjugates the one or more GalNAc moieties to the siRNA, in light of the teachings of Butler et al as presented above.
An ordinary skilled artisan would have been motivated to carry out the above modification because Butler et al already taught successfully double-stranded RNAi agents targeting TMPRSS6, and wherein the RNAi agents are conjugated to a ligand (e.g., one or more GalNac moieties attached via a bivalent or a trivalent branched linker) to be attached to the sense strand, antisense strand, or both strands, at the 3’-end, 5’-end, or both ends for at least enhanced targeting to a targeted cell or tissue; and that a ligand may improve nuclease resistance of a natural or modified oligonucleotide.
An ordinary skilled artisan would have a reasonable expectation of success in light of the teachings of Khvoraova et al and Butler et al, coupled with a high level of skill for an ordinary skilled artisan in the relevant art.
The modified siRNA or RNAi resulting from the combined teachings of Khvoraova et al and Butler et al is indistinguishable from and encompassed by the nucleic acid of the presently claimed invention.
Therefore, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Response to Argument
Applicant’s arguments related to the above 103 rejection in the Amendment filed on 10/17/2025 (page 17) have been fully considered, however, they are respectfully not found persuasive for the following reasons.
Applicant argued that currently amended claim 1 recites the limitation of claim 2, which is not rejected as allegedly being unpatentable over Khvorova in view of Butler. Accordingly, the claim amendments render the rejection moot. Applicant also argued that there is no teaching or suggestion in Khvorova to select SEQ ID NO: 1480590 from the millions of sequences in the Khvorova sequence listings for modification, and Butler does not remedy the deficiencies of Khvorova since Butler does not teach or suggest a nucleic acid for inhibiting expression of a TMPRSS6 gene comprising a first strand consisting of the sequence 5’-3’: aaccagaagaagcagguga (SEQ ID NO: 333) as recited in amended claim 1.
First, claim 2 was already rejected by Khvorova in the Non-Final office action dated 06/18/2025 (see the above 102(a)(1) rejection for the embodiment of claim 2 which is now incorporated in currently amended independent claim 1).
Second, the Butler reference was cited to complement the teachings of the Khvorova reference is at least for the issue of the nucleic acid of claim 1 conjugated to a ligand comprising (i) one or more GalNac moieties, and (ii) a linker, wherein the linker has a bivalent or trivalent branched structure that conjugates the one or more GalNAc moieties to the siRNA recited in dependent claims 5-6.
Third, since the rejection was made under 35 U.S.C. 103 each of the cited references does not have to teach every limitation of the instant claims. For example, the supplementary Butler reference does not have to teach or suggest a nucleic acid for inhibiting expression of a TMPRSS6 gene comprising a first strand consisting of the sequence 5’-3’: aaccagaagaagcagguga (SEQ ID NO: 333). It appears that Applicant considered each of the cited references in total isolation one from the other, without taking into consideration of the specific combined teachings of both Khvorova and Butler as set forth above. Please refer to the above 103 rejection for details.
Fourth, the teachings of Khvorova clearly include SEQ ID NO: 1480590 which is listed in the sequence listing as evidenced at least by the statement “Incorporated by reference of sequence listing submitted on compact disc” (col. 1, lines 21-23).
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Khvorova et al (US 7,691,997; IDS) in view of Butler et al (US 10,829,763) as applied to claims 1, 4-6, 8 and 18-19 above, and further in view of Rozema et al (US 2016/0272970) for the same reasons set forth in the Office Action dated 06/18/2025 (pages 10-11). The same rejection is restated below.
The combined teachings of Khvorova et al and Butler et al were presented above. However, none of the cited references teach or suggest specifically that the modified siRNA comprising a phosphorothioate linkage between the terminal one, two, or three 3’ nucleotides and/or 5’ nucleotides of the first strand and/or the second strand.
Before the effective filing date of the present application (04/05/2017), Rozema et al already disclosed a 26-mer RNAi agent having 1-4 modified phosphorothioate linkages in the sense strand, the anti-sense strand, or both the sense and anti-sense strand; and in an embodiment each of nucleotides 1’-2’, 2’-3’, 1-2, 2-3, 19’-20’, 20’-21’, 21’-22’, 22’-23’, 23’-24’, 21-22, 22-23, 23-24, 24-25, 25-26 is independently linked via a phosphorothioate linkage (see at least Abstract; Summary; and particularly paragraphs [0033]-[0037]; and FIG. 3).
Accordingly, it would have been obvious for an ordinary skilled artisan before the effective filing date of the present application to further modify the combined teachings of Khvoraova et al and Butler et al by also having phosphorothioate linkages among the 3 terminal 5’ and/or 3’ nucleotides of the sense and/or anti-sense strands in the modified dsRNA or RNAi, in light of the teachings of Rozema et al as set forth above.
An ordinary skilled artisan would have been motivated to further carry out the above modification because Rozema et al already disclosed a useful 26-mer RNAi agent having 1-4 modified phosphorothioate linkages in the sense strand, the anti-sense strand, or both the sense and anti-sense strand; and in an embodiment each of nucleotides 1’-2’, 2’-3’, 1-2, 2-3, 19’-20’, 20’-21’, 21’-22’, 22’-23’, 23’-24’, 21-22, 22-23, 23-24, 24-25, 25-26 is independently linked via a phosphorothioate linkage.
An ordinary skilled artisan would have a reasonable expectation of success in light of the teachings of Khvoraova et al, Butler et al and Rozema et al, coupled with a high level of skill for an ordinary skilled artisan in the relevant art.
The modified siRNA or RNAi resulting from the combined teachings of Khvoraova et al, Butler et al and Rozema et al is indistinguishable from and encompassed by the nucleic acid of the presently claimed invention.
Therefore, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Response to Argument
Applicant’s arguments related to the above 103 rejection in the Amendment filed on 10/17/2025 (page 18) have been fully considered, however, they are respectfully not found persuasive for the following reasons.
Once again, Applicant argued basically that currently amended claim 1 recites the limitation of claim 2, which is not rejected as allegedly being unpatentable over Khvorova in view of Butler. Accordingly, the claim amendments render the rejection moot.
First, claim 2 was already rejected by Khvorova in the Non-Final office action dated 06/18/2025 (see the above 102(a)(1) rejection for the embodiment of claim 2 which is now incorporated in currently amended independent claim 1).
Second, the Rozema reference was cited to further complement the combined teachings of the Khvorova reference and the Butler reference is for the limitation recited in dependent claim 9. Please refer to the above 103 rejection for details.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Khvorova et al (US 7,691,997; IDS) in view of Butler et al (US 10,829,763) as applied to claims 1, 4-6, 8 and 18-19 above, and further in view of Frauendorf et al (WO 2017/174657; IDS) for the same reasons set forth in the Office Action dated 06/18/2025 (pages 11-12). The same rejection is restated below.
The combined teachings of Khvorova et al and Butler et al were presented above. However, none of the cited references teach or suggest a conjugated nucleic acid having the elected structure recited in claim 7.
Before the effective filing date of the present application (04/05/2017), Frauendorf et al already disclosed a glycoconjugate having the structure that is identical to the elected structure recited in claim 7 to be conjugated to at least an RNAi or an siRNA (see at least Abstract; Summary of the Invention; pages 12-17; and particularly the structure on page 12). Frauendorf et al stated “These conjugate compounds have been shown to have improved potency and duration in vivo” (page 2, lines 26-27).
Accordingly, it would have been obvious for an ordinary skilled artisan before the effective filing date of the present application to further modify the combined teachings of Khvoraova et al and Butler et al by also selecting the glycoconjugate of Frauendorf to conjugate to the modified dsRNA or RNAi.
An ordinary skilled artisan would have been motivated to further carry out the above modification because Frauendorf et al already disclosed a glycoconjugate having the structure that is identical to the elected structure recited in claim 7 having improved potency and duration in vivo for conjugation an RNAi.
An ordinary skilled artisan would have a reasonable expectation of success in light of the teachings of Khvoraova et al, Butler et al and Frauendorf et al, coupled with a high level of skill for an ordinary skilled artisan in the relevant art.
The modified dsRNA or RNAi resulting from the combined teachings of Khvoraova et al, Butler et al and Frauendorf et al is indistinguishable from and encompassed by the nucleic acid of the presently claimed invention.
Therefore, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Response to Argument
Applicant’s arguments related to the above 103 rejection in the Amendment filed on 10/17/2025 (pages 18-19) have been fully considered, however, they are respectfully not found persuasive for the following reasons.
Once again, Applicant argued basically that currently amended claim 1 recites the limitation of claim 2, which is not rejected as allegedly being unpatentable over Khvorova in view of Butler. Accordingly, the claim amendments render the rejection moot.
First, claim 2 was already rejected by Khvorova in the Non-Final office action dated 06/18/2025 (see the above 102(a)(1) rejection for the embodiment of claim 2 which is now incorporated in currently amended independent claim 1).
Second, the Frauendorf reference was cited to further complement the combined teachings of the Khvorova reference and the Butler reference is for the limitation recited in dependent claim 7. Please refer to the above 103 rejection for details.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Amended claims 1, 3-11 and 17-19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 and 14-21 of copending Application No. 18/288,427 (reference application) for the same reasons set forth in the Office Action dated 06/18/2025 (page 19). The same rejection is restated below.
Although the claims at issue are not identical, they are not patentably distinct from each other because a method of preventing, decreasing the risk of suffering from, or treating a myeloproliferative disorder using a pharmaceutically effective amount of a composition comprising a double-stranded nucleic acid that is capable of inhibiting expression of TMPRSS6 in claims 1-12 and 14-21 of copending Application No. 18/288,427 encompasses a nucleic acid for inhibiting expression of TMPRSS6 in the application being examined and, therefore, a patent to the genus would, necessarily, extend the rights of the species or sub- should the genus issue as a patent after the species of sub-genus.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
In the Amendment filed on 10/17/2025 (page 21), Applicant simply requested that the above provisional nonstatutory double patenting rejection be held in abeyance until allowable subject matter is indicated for the present application.
Conclusion
No claim is allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Quang Nguyen, Ph.D., at (571) 272-0776.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s acting SPE, James Douglas (Doug) Schultz, Ph.D., may be reached at (571) 272-0763.
To aid in correlating any papers for this application, all further correspondence regarding this application should be directed to Group Art Unit 1631; Central Fax No. (571) 273-8300.
Any inquiry of a general nature or relating to the status of this application or proceeding should be directed to (571) 272-0547.
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/QUANG NGUYEN/Primary Examiner, Art Unit 1631
Sequence 1480590,
Patent No. 7691997
Functional and Hyperfunctional siRNA
LENGTH: 19
ORGANISM: Homo sapiens
Query Match 100.0%; Score 19; DB 15; Length 19;
Best Local Similarity 94.7%;
Matches 18; Conservative 1; Mismatches 0; Indels 0; Gaps 0;
Qy 1 AACCAGAAGAAGCAGGUGA 19
||||||||||||||||:||
Db 19 AACCAGAAGAAGCAGGTGA 1
Sequence 1480590,
Patent No. 7691997
Functional and Hyperfunctional siRNA
LENGTH: 19
ORGANISM: Homo sapiens
Query Match 100.0%; Score 19; Length 19;
Best Local Similarity 100.0%;
Matches 19; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 UCACCUGCUUCUUCUGGUU 19
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Db 1 UCACCUGCUUCUUCUGGUU 19
Prosecution Insights