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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 02/25/2026 has been entered.
Status of the Claims
Claims 1, 3-21, 59-71, 74, 77-117, 130-132 are pending.
Claims 13-19, 21, 59, 62, 65-71, 78, 80, 83-103, 105, 109-114, 116-117, and 130-132 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention or species as previously indicated, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 06/06/2024.
Claims 1, 3-12, 20, 60, 61, 63, 64, 74, 77, 79, 81-82, 104, 106-108, 115 are under consideration.
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 74 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 74 has been amended to recite a short interfering nucleic acid (siNA) molecule comprising: (a) a sense strand comprising a first nucleotide sequence comprising a nucleotide sequence and modification pattern of any one SEQ ID NOs: 103-158, 205-260, 307- 362, and 415-444; and (b) an antisense strand comprising a second nucleotide sequence comprising a nucleotide sequence and modification pattern of any one of SEQ ID NOs: 159-204, 261-306, 363-409, 445-533, and 536-539.
That is, the claim has been amended to explicitly require that the siNA must comprise the modification pattern as set forth in the nucleotide sequence of the indicated SEQ ID NOs. However, the nucleotides sequence set forth in SEQ ID NO: 435 (the elected sense strand species) and the nucleotide sequence set forth in SEQ ID NO: 513 (the elected antisense strand species) do not include any chemical modifications (see sequence information below). Since neither SEQ ID NO: 435 nor SEQ ID NO: 513 comprise any modification pattern, it is unclear what modification pattern the claim is drawn to. Furthermore, the broadest reasonable interpretation of the claim is that the siNA can comprise any modification pattern or no modification pattern, given that none are explicitly present in SEQ ID NO: 435 and SEQ ID NO: 513.
SEQUENCE LISTING INFORMATION FOR SEQ ID NO: 435:
<210> 435
<211> 19
<212> RNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
oligonucleotide
<400> 435
gugguggacu ucucucaau 19
SEQUENCE LISTING INFORMATION FOR SEQ ID NO: 513:
<210> 513
<211> 21
<212> RNA
<213> Artificial Sequence
<220>
<223> Description of Artificial Sequence: Synthetic
oligonucleotide
<400> 513
auugagagaa guccaccacg a 21
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 (i.e., changing from AIA to pre-AIA ) 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 74 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by U.S. 2017/0035796 (hereafter “Wooddell”, of record).
Claims interpretation: As indicated in the rejection above, claim 74 has been amended to require that the sense strand comprises the nucleotide sequence and modification pattern of SEQ ID NO: 435 (the elected sequence), and to require that the antisense strand comprises the nucleotide sequence and modification pattern of SEQ ID NO: 513 (the elected sequence). However, neither SEQ ID NO: 435 nor SEQ ID NO: 513 include any modification pattern in the nucleotide sequence (see sequence information above). Therefore, given the broadest reasonable interpretation, the claim encompasses an siNA wherein the sense strand comprises the nucleotide sequence of SEQ ID NO: 435 and the antisense strand comprises the nucleotide sequence of SEQ ID NO: 513 including any modification pattern or no modification pattern at all.
As indicated in the previous Office Action, Wooddell teaches an siNA molecule with a sense strand that comprising SEQ ID NO: 435 and an antisense strand that comprises SEQ ID NO: 513. Specifically, Wooddell teaches RNAi duplex AD04003 (Table 2) comprises the 21-nucleotide antisense strand AM5054-AS asUfsusGfaGfaGfaAfgUfcCfaCfcAfcusu, identified as Wooddell’s SEQ ID NO: 407 (see Table 1A), and 22 nucleotide sense strand identified as Wooddell’s SEQ ID NO: 636 AM05046-SS (NAG25)sasaguggugGfAfCfuucucucaaus(invAb) (See Table 1B). It is noted that instant SEQ ID NO: 435 (SS) is identical to the nucleotide sequence of Wooddell’s SEQ ID NO: 636 (SS), and instant SEQ ID NO: 513 (AS) is identical to the nucleotide sequence of Wooddell’s SEQ ID NO: 407 (AS).
Therefore, Wooddell anticipates claim 74
Response to Arguments
Applicant’s arguments have been fully considered but are not persuasive.
Applicant argues that the specification identifies a modification pattern for SEQ ID NO: 435 on pages 347-348 of the specification.
In response, Applicant’s arguments are not persuasive because the sequence listing does not include any modification pattern present in the nucleotide sequence. It is acknowledged that Table 4 on pages 345-347 of the specification indicates a sequence associated with SEQ ID NO: 435 that has a chemical modification pattern. However, given that SEQ ID NO: 435 in the sequence listing does not include any chemical modification pattern, it is clear that SEQ ID NO: 435 is limited to a specific nucleotide sequence, but it is not clear that merely referring to SEQ ID NO: 435 limits the nucleotide sequence to any particular chemical modification pattern. It is noted that page 345 does provide support for the specific modification pattern that may be present in the sense strand nucleotide sequence of SEQ ID NO: 435 (and the corresponding antisense nucleotide sequence of SEQ ID NO: 513), but the claim as written does not necessarily require any specific modification pattern. Applicant may wish to consider amending claim 74 to include the specific nucleotide sequence and modification pattern set forth in Table 4 for SEQ ID NO: 435, as well as the appropriate nucleotide sequence and modification pattern for SEQ ID NO: 513 which would obviate this rejection and the rejection under 35 U.S.C. § 112(b) above.
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 (i.e., changing from AIA to pre-AIA ) 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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) 1, 3-12, 60, 61, 63, 64, 81, 82, 104, 106-108, 115 is/are rejected under 35 U.S.C. 103 as being unpatentable over U.S. 2017/0035796 (hereafter “Wooddell”, of record).
Wooddell, as applied to the instant claims, teaches an siNA molecule with a sense strand comprising SEQ ID NO: 636 (instant SEQ ID NO: 40 which is the same nucleotide sequence as SEQ ID NO: 435) and an antisense strand comprising SEQ ID NO: 407 (instant SEQ ID NO: 88 which is the same nucleotide sequence as instant SEQ ID NO: 513). That is, Wooddell teaches RNAi duplex AD04003 (Table 2) comprises the 21-nucleotide antisense strand AM5054-AS, identified as Wooddell’s SEQ ID NO: 407 wherein the unmodified sequence is Wooddell’s SEQ ID NO: 97 (see Table 1A), and a 22 nucleotide sense strand identified as Wooddell’s SEQ ID NO: 636 AM05046-SS wherein the unmodified sequence is Wooddell’s SEQ ID NO: 202 (See Table 1B), as described in the rejection above.
Wooddell does not teach the specific pattern of chemical modifications to the siNA required by the instant claims.
However, Wooddell does teach siNA with various patterns of chemical modifications, including siNA having chemical modification pattern as required by the instant claim. For instance, Wooddell teaches siNA duplex AD00003 comprising SS AM00005-SS and AS AM00006-AS (e.g., see TABLE 2) wherein AM00005-SS comprises 15 nucleotides that are modified with either 2’-O-methyl or 2’-fluoro nucleotides, at least 11 nucleotides are modified with 2’O-methyl modifications and at least 4 nucleotides are 2’-fluoro modified including at positions 8, 10, 12, 14, 16, 18, (see Table 1B), and wherein AM00006-AS comprises 15 nucleotides that are modified with either 2’-O-methyl or 2’-fluoro nucleotides, at least 11 nucleotides are modified with 2’O-methyl modifications and 3 to 6 nucleotides are 2’-fluoro modified including at positions, 2, 6, 8, 10, 14, 16 (see Table 1A).
Regarding claim 3, Wooddell teaches an siNA with a first strand (sense strand) that comprises 16 or more modified nucleotides independently selected from 2’-O-methyl modified nucleotide and 2’-fluoro modified nucleotide (see above, all modified nucleotides).
Regarding claim 4, Wooddell teaches an siNA that comprises at least 70%, 75%, 80%, 85%, 90%, 95% or 100% of the nucleotides in the first nucleotide sequence (sense strand) are modified nucleotides independently selected from a 2' -0-methyl nucleotide and a 2'-fluoro nucleotide (see above, all modified nucleotides).
Regarding claim 5, Wooddell teaches at least 2 modified nucleotides of the first strand (sense strand) are 2’-fluoro nucleotides (see above, 2’-fluoro at position 9-11).
Regarding claim 6, Wooddell teaches an siRNA wherein the second strand (antisense strand) comprising at least 16 modified nucleotides independently selected from a 2' -0-methyl nucleotide and a 2'-fluoro nucleotide (see above, all modified nucleotides).
Regarding claim 7, Wooddell teaches an siNA wherein 100% of the nucleotides in the second nucleotide sequence are modified nucleotides independently selected from a 2'-O-methyl nucleotide and a 2'-fluoro nucleotide (see above, 100% modified).
Regarding claim 8, Wooddell teaches an siNA wherein at least 2, 3, 4, 5, or 6 modified nucleotides of the second nucleotide sequence are 2'- fluoro nucleotides (see above).
Regarding claim 9, Wooddell teaches an siNA comprising 1 or more phosphorothioate internucleoside linkage in the sense strand and/or antisense strand (see above, where s=phosphorothioate linkages).
Regarding claim 10, Wooddell teaches an siNA comprising a galactosamine (see above where NAG is N-acetylgalactosamine (NAG) as indicated in [0058]).
Regarding claim 11, Wooddell teaches an siNA wherein at least 1, nucleotide at position 3, 5, 7, 8, 9, 10, 11, 12, or 17 from the 5' end of the first nucleotide sequence is a 2'-fluoro nucleotide (see above where position 9, 10 and 11 are 2’-fluoro (GfAfCf)).
Regarding claim 12, Wooddell teaches an siNA wherein at least 1 nucleotide at position 2, 5, 6, 8, 10, 14, 16, 17, and/or 18 from the 5' end of the second nucleotide sequence is a 2'-fluoro nucleotide (see above where at least position 8, 10, 14, 16, 18 of the antisense strand are 2’-fluoro nucleotides (Gf, Af, Cf, Cf, Af)).
Regarding claim 60, Wooddell teaches an siNAwherein the sense strand comprises at least 1 phosphorothioate linkage (see above where s=phosphorothioate linkage).
Regarding claim 61, Wooddell teaches an siNA with a phosphorothioate internucleoside linkage between the nucleotides at positions 1 and 2 from the 5' end of the first nucleotide sequence; (ii) a phosphorothioate internucleoside linkage between the nucleotides at positions 2 and 3 from the 5' end of the first nucleotide sequence. Specifically, see AM04660-SS gsgsuggsCfuUfCfUfcucaAfUfuuua(NAG13) (Table1B, where s=phosphorothioate)
Regarding claim 62, Wooddell teaches an siNA wherein the antisense strand further comprises TT sequence adjacent to the second nucleotide sequence. For example, see AM000006-AS dTAfcCfaAfuUfuAfuGfcCfuAfcAfgdTsdT (where dTsdT is two Ts connected by a phosphorothioate linker (s)).
Regarding claim 63, Wooddell teaches an siNA wherein the antisense strand further comprises at least 1 phosphorothioate internucleoside linkage (see above).
Regarding claim 64, Wooddell teaches an siNA, wherein the antisense strand comprises a phosphorothioate internucleoside linkage between nucleotides at positions 1 and 2 from the 5’ end of the second nucleotide sequence (see above).
Regarding claim 81, Wooddell teaches an siNA which further comprises a galactosamine. For instance, see the siNA comprising AM05046-SS (NAG25)sasaguggugGfAfCfuucuc-ucaaus(invAb) (See Table 1B), wherein (NAG25) comprises a galactosamine.
With respect to claim 82, although Wooddell teaches that the siNA can comprise a galactosamine (as indicated in the 102 rejection above), and further explicitly indicates that the galactosamine can be N-acetylgalactosamine (GalNAc or NAG) including multiple (multimeric) galactosamines (see [0107]), and specifically teaches a siNA with a trimer n-acetylgalactosamine identified as [NAG25], Wooddell does not teach the use of the GalNAc of Formula (VII).
It is noted that Wooddell teaches,
“The affinities of numerous galactose derivatives for the asialoglycoprotein receptor have been studied… or are readily determined using methods well known and commonly used in the art. Other terms common in the art for galactose trimer having three terminal galactose derivatives include tri-antennary galactose, tri-valent galactose. Other terms common in the art for galactose trimer include galactose cluster. It is known that tri-antennary galactose derivative clusters are bound to the ASGPr with greater affinity than bi-antennary or mono-antennary galactose derivative structures…” (References to citations removed).
Regarding claim 104, Wooddell teaches that the siNAs target a gene from Hepatitis B Virus (HBV). For example, see abstract.
Regarding claims 106-108, Wooddell teaches the siNA molecules comprising a 21 nucleotide antisense strand AM5054-AS asUfsusGfaGfaGfaAfgUfcCfaCfcAfcusu, identified as Wooddell’s SEQ ID NO: 407 (see Table 1A), which is identical to SEQ ID NO: 513, and a 22 nucleotide sense strand identified as Wooddell’s SEQ ID NO: 636 AM05046-SS (NAG25)sasaguggugGfAfCfuucucucaaus(invAb) (See Table 1B), identical to instant SEQ ID NO: 435. Alignment of the two strands (Wooddell’s 21 nucleotide AS SEQ ID NO: 407 and 22 nucleotide SS SEQ ID NO: 636) indicates that at least one end of the dsNA complex would be a blunt end and one end would have an overhang nucleotide. Furthermore, the dsNA of Wooddell having AM05046-SS and AM5054-AS is identical to ds-siNA-0138 which has the elected species SEQ ID NO: 435 and SEQ ID NO: 513.
Regarding claim 115, Wooddell teaches that the siNA can be formulated with a pharmaceutically acceptable excipient to make a pharmaceutical composition (e.g., see [0017], [0122], claims 18-19, etc.).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art prior to the day the claimed invention was filed to modify the chemical modification pattern required by the instant claims with a reasonable expectation of success. Since Wooddell teaches that the chemical modifications including their specific location in siNA molecules was known, it would have been a matter of applying a chemical modification known in siNAs to the specific duplex siNA comprising Wooddell’s SS- SEQ ID NO: 202 and AS-SEQ ID NO: 97.
It also would have been further prima facie obvious to one of ordinary skill in the art prior to the day the claimed invention was filed to further modify the modified siNA duplex taught by Wooddell as indicated above and use a different known tri-valent GalNAc, including a GalNAc of Formula (VII) as required by claim 82, with a reasonable expectation of success. Official notice is taken that the GalNAc of Formula (VII) was previously known in the art.
The combination of prior art satisfies the factual inquiries as set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966). Once this has been accomplished the holdings in KSR can be applied (KSR International Co. v. Teleflex Inc. (KSR), 550 USPQ2d 1385 (2007):
“Exemplary rationales that may support a conclusion of obviousness include: (A) Combining prior art elements according to known methods to yield predictable results; (B) Simple substitution of one known element for another to obtain predictable results; (C) Use of known technique to improve similar devices (methods, or products) in the same way; (D) Applying a known technique to a known device (method, or product) ready for improvement to yield predictable results; (E) “Obvious to try” – choosing from a finite number of identified, predictable solutions, with a reasonable expectation of success; (F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art; (G) Some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.”
In this case, it would have been a matter of (A) Combining the prior art elements (the specific double stranded nucleotides sequences and the specific pattern of modifications) according to known methods to yield predictable results; (B) Simple substitution of one known element for another (substituting the known chemical modification to the specific double stranded nucleotide sequences) to obtain predictable results; or (E) “Obvious to try” the combination of the specific chemical modifications with the specific double stranded siNA nucleotides sequences, with a reasonable expectation of success.
Response to Arguments
With respect to the pending rejection of claims under 35 USC 103 as indicated above, Applicant's arguments have been fully considered but they are not persuasive.
Applicant argues that Wooddell does not disclose the claimed modification patterns on the specific HBV siNA duplexes at issue, nor teach that the modification patterns are transferrable and thus the “combination of known elements” and “obvious to try” rationales do not apply.
In response it is acknowledged that Wooddell does not disclose the claimed modification patterns on the specific HBV siNA duplexes at issue. However, as indicated in the rejection, Wooddell teaches an siNA having sense and antisense strands with the required nucleotide sequences, and further teaches many different chemical modification patterns that can be applied to siNA molecules and explicitly teaches that chemical modification of the RNAi molecule, including the incorporation of 2’-O-mehtyl-ribonucleotides and 2’-Fluoro-ribonucleotides, “when used in various polynucleotide constructs are shown to preserve polynucleotide activity in cells while at the same time increasing the serum stability of these compounds… and also minimize the possibility of activating interferon activity in humans.” (see [0115]). Furthermore, contrary to the assertion that Wooddell does not teach that the modification patterns are transferable, Wooddell teaches different siNA duplex nucleotide sequences which have the modification pattern required by the instant claims. For instance, Wooddell teaches that the modification pattern applied to the sense strand sequence AM-00005-SS (as indicated above) is also applied to the sense strand sequence AM-00007-SS which is a different nucleotide sequence (see Table 1B), and that the modification pattern applied to the antisense strand sequence AM-00006-AS (as indicated above) is also applied to the antisense strand sequence AM-00008-AS which is also a different nucleotide sequence (see Table 1A). Thus, Wooddell does teach that the modification pattern is applicable to different siNA nucleotide sequences (i.e., they are transferrable), and the “combination of known elements” and “obvious to try” rationales are applicable.
Applicant also argues that the present application provides in vivo evidence of non-obvious, superior effects for the claimed pattern on the claimed sequences, referring to FIGs. 4-7, 9-16, ds-siNA duplexes ds-siNA-0160, ds-siNA-0163, ds-siNA-0165, ds-siNA-0166, ds-siNA-0169, etc.
In response, it is noted that of the indicated ds-siNA duplexes only one has the required sense strand nucleotide sequence (ds-siNA-0165), but this duplex does not have the required antisense nucleotide sequence. That is, ds-siNA-0165 comprises sense strand SEQ ID NO: 435 and antisense strand SEQ ID NO: 502 (see Table 10),while the elected ds-siNA species is SS-SEQ ID NO:435 and AS-SEQ ID NO: 513. It is also noted that it does not appear that the modification pattern of ds-siNA-0165 meets the modification pattern requirement of claim 1 at least because the antisense strand modification pattern of dsw-siNA-0165 only has 2’=F modified nucleotides at positions 1 and 13 (e.g., see Tables 7-9, etc.). Accordingly, the evidence applicant refers do does not appear to be commensurate in scope with the claimed ds-siNA duplex modification required by the claims. Furthermore, Wooddell’s teaching of the required modification pattern applied to different ds-siNA molecules provides a basis for using the modification on other ds-siNA duplexes and provides a reasonable expectation of success when doing so.
Therefore, Applicant’s arguments are not persuasive.
Claims 77 and 79 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. 2017/0035796 (hereafter “Wooddell”, of record), in view of WO2010141726 (hereafter “Basu”)
Wooddell, as applied to the instant claims is described in the rejection above.
With respect to claim 77, 79, although Wooddell generally teaches that locked nucleotides are one of the types of modified nucleotides that can be used the siNA (see [0045]), Wooddell does not provide any specific examples of siNA comprising locked nucleotides, and does not teach a locked nucleotide of Formula (IV).
Basu teaches locked nucleic acids (LNAs) can be used to stabilize dsRNAs and improve dsRNA performance (see page 77, second to last paragraph). Basu also explicitly teaches that LNA is incorporated into the 5’ terminus of the sense strand (see page 82, second to last paragraph). Although Basu does not provide the specific structure of the LNA, Basu provides several references indicating “LNA’s are well known to a skilled artisan” citing several references (see page 82, second to last paragraph); furthermore, official notice is also taken that the LNA of formula (IV) was known.
Therefore, it also would have been further prima facie obvious to one of ordinary skill in the art prior to the day the claimed invention was filed further modify the siNA duplex taught by Wooddell and use LNA, including a LNA of Formula (IV), at the 5’ terminal end of the sense strand of Wooddell’s siNA, with a reasonable expectation of success. The motivation would be to stabilize the siNA and improve its performance. As such, KSR’s rationales (A), (B), and/or (E), as indicated above apply here.
Therefore, the instant claims are unpatentable under 35 USC 103.
Response to Arguments
Applicant argues that the rejection fails for at least the same reasons discussed above as claims 77, 79 depend directly on claim 1.
This is not persuasive for the reasons indicated in the response to arguments against the rejection of claim 1 as indicated above.
New Claim Rejections - 35 USC § 103
Claim 20 is rejected under 35 U.S.C. 103 as being unpatentable over U.S. 20170035796 (hereinafter “Wooddell”; of record – IDS citation) in view of U.S. 20200038506 (hereinafter “Sepp-Lorenzino”).
Regarding claim 20, As indicated above, Wooddell teaches a double stranded siNA molecule that has a sense strand comprising SEQ ID NO: 636 (identical to instant SEQ ID NO: 40) and an antisense strand comprising SEQ ID NO: 407 (identical to instant SEQ ID NO: 88).
Wooddell does not teach that the double stranded siNA molecule comprising sense strand SEQ ID NO: 40 and complementary strand SEQ ID NO: 88 has the chemical modification pattern required by Formula (IX) in claim 20
Regarding the chemical modification pattern required for the sense strand of Formula (IX), Wooddell teaches an siNA having a sense strand oligonucleotide represented by 5’- AAAABABBBAAAAAAAAAA wherein each A is a 2’-O-methyl nucleotide and each B is a 2’-fluoro nucleotide (i.e., 2’-F at positions 5 and 7-9, all other positions 2’-O-methyl)), identified as AM04659-SS in Table 1B (see page 18). The AM04659 modified oligonucleotide meets the structural limitations of the sense strand of claim 20.
Although Wooddell does not teach that the antisense strand has the modification pattern required by Formula (IX) as set forth in claim 20, Wooddell does teach an antisense strand having a modification pattern very similar to the antisense strand modification pattern required by the claims. Formula (IX) of claim 20 encompasses an antisense strand modification pattern that is ABAAABAAAAAAABABAAACC wherein each A and C is a 2’-O-methyl nucleotide and each B is a 2’-fluoro nucleotide (i.e., 2’-F positions at 2, 6, 14, 16, all other positions 2’-O-methyl). Wooddell teaches an antisense oligonucleotide with a modification pattern ABAAABABBAAAABABAAAAA (i.e., 2’-F positions at 2, 6, 8-9, 14, 16, all other positions 2’-O-methyl) identified as AM04661-AS in Table 1A on page 11), which is similar to the required modification pattern. Thus, Wooddell teaches a duplex of AM04659-SS and AM04661-AS, identified as AD03669 in Table 2 on page 21, which is a duplex that has a sense strand having the required modification pattern and an antisense strand having a modification pattern very similar to the required modification pattern.
Although Wooddell does not teach that the antisense strand has a modification pattern required by Formula(IX), the prior art does teach double stranded siNA molecules for inhibiting Hepatitis B virus gene expression including an siNA having an antisense strand with the required modification pattern. For instance, Sepp-Lorenzino teaches an siNA for inhibiting Hepatitis B virus gene expression with antisense strand A-127930 (see Table 3 on page 61), having the modification pattern ABAAABAAAAAAABABAAACC wherein each A and C is a 2’-O-methyl nucleotide and each B is a 2’-fluoro nucleotide (where 2’-F is at positions 2, 6, 14, 16, all other positions 2’-O-methyl)
Therefore, it would have been prima facie obvious to one of ordinary skill in the art, prior to the day the claimed invention was filed, to combine the teachings of Wooddell and Sepp-Lorenzino and arrive at the double stranded siNA molecule required by the claim 20 with a reasonable expectation of success. That is, since siNAs were known as effective inhibitors of HBV gene expression, including an siNAs having the nucleotide sequences required for the sense and antisense strand (as taught by Wooddell), and further considering that the chemical modification patterns required for both the sense strand (as taught by Wooddell) and the antisense strand (as taught by Sapp-Lorenzino), it would have been a matter of being obvious to try combining what was already known in the prior art (i.e., substituting other known effective chemical modification patterns known for the same purpose) to arrive at the claimed invention. There would have been a reasonable expectation of success based on the positive results indicated in the cited prior art references. Furthermore, KSR rationales (A), (B), and/or (E), as previously indicated apply here.
Maintained Double Patenting Rejection
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.
Claims 1, 3-12, 20, 60, 61, 63, 64, 74, 77, 79, 81-82, 104, 106-108, 115 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 11,549,110. Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are broader in scope than the claims of the ‘110 patent. Since broader genus claims are anticipated by the narrower species they encompass, the instant claims are anticipated by the claims of the ‘110 patent.
Response to Arguments
With respect to the non-statutory double patenting rejection, Applicant's arguments have been fully considered but they are not persuasive.
Applicant argues that the rejection does not provide the required substantive analysis. It is noted that MPEP 804 states:
Nonstatutory double patenting includes rejections based on anticipation, a one-way determination of "obviousness," or a two-way determination of "obviousness." It is important to note that the "obviousness" analysis for "obviousness-type" double-patenting is "similar to, but not necessarily the same as, that undertaken under 35 U.S.C. 103." In re Braat, 937 F.2d 589, 592-93, 19 USPQ2d 1289, 1292 (Fed. Cir. 1991) (citing In re Longi, 759 F.2d 887, 892 n.4, 225 USPQ 645, 648 n.4 (Fed. Cir. 1985))…
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)…
MPEP 804 II. B. 2. Anticipation analysis states:
A nonstatutory double patenting rejection is appropriate where a claim in an application under examination claims subject matter that is different, but not patentably distinct, from the subject matter claimed in a prior patent or a copending application. The claim under examination is not patentably distinct from the reference claim(s) if the claim under examination is anticipated by 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, 1052, 29 USPQ2d 2010, 2015-16 (Fed. Cir. 1993). This type of nonstatutory double patenting situation arises when the claim being examined is, for example, generic to a species or sub-genus claimed in a conflicting patent or application, i.e., the entire scope of the reference claim falls within the scope of the examined claim. In such a situation, a later patent to a genus would, necessarily, extend the right to exclude granted by an earlier patent directed to a species or sub-genus. In this type of nonstatutory double patenting situation, an obviousness analysis is not required for the nonstatutory double patenting rejection. The nonstatutory double patenting rejection in this case should explain the fact that the species or sub-genus claimed in the conflicting patent or application anticipates the claimed genus in the application being examined and, therefore, a patent to the genus would improperly extend the right to exclude granted by a patent to the species or sub-genus should the genus issue as a patent after the species or sub-genus.
Such is that case here, where the instant claims are broader in scope than the claims of the ‘110 patent, as indicated in the rejection. Since broader genus claims are anticipated by the narrower species they encompass, the instant claims are anticipated by the claims of the ‘110 patent. In this type of nonstatutory double patenting situation, an obviousness analysis is not required for the nonstatutory double patenting rejection, as indicated in MPEP 804.
Therefore, the rejection is appropriate and Applicants’ arguments are not persuasive.
New Double Patenting Rejections
Claim 20 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 31-33 of copending Application No. 18/059,561 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
Instant claim 20 sets forth the chemical modification pattern of Formula (IX) for the double stranded siNA molecule and requires that the sense strand is any one of SEQ ID Nos 1-56. Claim 31 of the ‘506 application is drawn to a siNA molecule having a modification pattern represented by Formula (VII), which overlaps in scope with the modification pattern Formula(IX). Claims 32-33 of the ‘561 application limit the nucleotide sequence of the sense strand of the siNA to SEQ ID NO: 40 and a complementary strand, which is clearly encompassed by the larger genus set forth in instant claim 20 (SEQ ID Nos: 1-56 and complementary strand). Therefore, instant claim 20 overlaps in scope with claims 31-33 of the ‘561 application, thus the claims are not patentably distinct and a nonstatutory double patenting rejection is appropriate.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 20 rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of copending U.S. Patent No. 12,129,469. Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
The following rejection is in view of the decision of the Court of Appeals for the Federal Circuit in Pfizer Inc, v Teva pharmaceuticals USA Inc., 86 USPQ2d 1001, at page 1008 (March 2008), which indicates that there is no patentable distinction between claims to a product and a method of using that product disclosed in the specification of the application and that the preclusion of such a double patenting rejection under 35 USC 121 does not apply where the present application is other than a divisional application of the patent application containing such patentably indistinct claims.
Instant claim 20 is drawn to a double stranded siNA molecule and sets forth the chemical modification pattern of Formula (IX) for the double stranded siNA molecule and further requires that the sense strand is any one of SEQ ID Nos 1-56 and a complementary antisense strand. Claim 1 of the ‘469 patent is drawn to a method of treatment using a double stranded siNA molecule having a modification pattern represented by Formula (VII), which overlaps in scope with the modification pattern Formula (IX), and further limits the nucleotide sequence of the siNA molecule to a sense strand having SEQ ID NO: 40 and a complementary antisense strand. Therefore, the siNA molecule of instant claim 20 overlaps in scope with the siNA molecule of claim 1 of the ‘561 application. Accordingly, instant claim 20 and claim 1of the ‘469 patent are related as a product and a method of using that product disclosed in the specification of the application, and a nonstatutory double patenting rejection is appropriate.
Conclusion
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J. E. Angell
Primary Examiner
Art Unit 1637
/J. E. ANGELL/Primary Examiner, Art Unit 1637
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