DETAILED ACTION
Confirmation of Applicants’ election without traverse of SEQ ID NO: 149 and 150 and Group I in the reply filed on October 20 2025 is acknowledged.
Claims 1, 4, 11, 15, 17, 32-35, 41-42, 44, 47-55, 60-66 and 83-85 were/stand cancelled. Claims 2-3, 5-8, 12, 16, 18, 20, 22, 28-31, 36-38, 45-46, 56-58 and 68 were amended. Claims 2-3, 5-10, 12-14, 16, 18-31, 36-40, 43, 45-46, 56-59 and 67-82 are pending. In light of the amendments filed October 20 2025, claim 6 is no longer considered withdrawn as it is directed to the portion of ATXN 3 corresponding to SEQ ID No: 149/150. Claims 67-82 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on February 4 2025 (invention) and April 9 2025 (species) with confirmation in the response filed October 20 2025. Accordingly, claims 2-3, 5-10, 12-14, 16, 18-31, 36-40, 43, 45-46 and 56-59 are being examined on the merits herein.
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 .
Information Disclosure Statement
The information disclosure statements (IDS) submitted on October 20 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Objections/Rejections
The amendments filed October 20 2025 are sufficient to overcome the objection of claims 12, 16 and 57. The acronym has been spelt out the first time the acronyms are used.
The amendments filed October 20 2025 are sufficient to overcome the objection of claim 18. The additional dash was removed.
The amendments/arguments filed October 20 2025 are sufficient to overcome the rejection of claims 29-30 under 35 USC 112b. The claim was amended to clarify the nucleoside is modified. These claim are interpreted as requiring an additional modification to the modifications recited in claim 2.
The amendments filed October 20 2025 are sufficient to overcome the rejection of claim 5 under 35 U.S.C. 112(d). Claim 5 is now of a different scope than claim 2.
The amendments filed October 20 2025 are sufficient to overcome the rejection of the claims on the ground of nonstatutory double patenting over US Patent No. 10533175; 11293025; 11583548; 11434488; copending Application No. 18168004; copending Application No. 17678311; and copending Application No. 18485724. Specifically the claims now all depend from claim 2 (which was not rejected on the ground of nonstatutory double patenting) and recites two specific sequences which are not claimed in the patents or copending applications.
Claim Interpretation
Claims 58-59 contain the transitional language “consisting essentially of”. For the purposes of searching for and applying prior art under 35 U.S.C. 102 and 103, absent a clear indication in the specification or claims of what the basic and novel characteristics actually are, “consists essentially of” will be construed as equivalent to “comprising.” If an applicant contends that additional steps or materials in the prior art are excluded by the recitation of “consisting essentially of,” applicant has the burden of showing that the introduction of additional steps or components would materially change the characteristics of applicant's invention. PPG Industries Inc. V Guardian Industries Corp. 48 USPQ2d 1351 (Fed. Cir. 1998) and In re De Lajarte 337 F.2d 870, 143 USPQ 256 (CCPA 1964) See MPEP 2111.03.
The instant specification does not define the term “consisting essentially of” in a manner that would allow one skilled in the art to determine what basic and novel characteristics are being materially affected.
Response to Arguments
Applicants’ arguments filed October 20 2025 have been fully considered but they are not persuasive.
Applicants argue that the examiner should consider the disclosure of the application as a whole and as a specific definition is not required in order to interpret claim terms.
Applicants arguments are not persuasive. Nothing in the response points to where in the specification the basic and novel characteristics are discussed. Nor do the remarks indicate what components in the cited prior art are excluded by the recitation. That is the reason for the statements above. The examiner is interpreting, for art purposes, the recitation of consisting essentially of as comprising. If an applicant contends that additional steps or materials in the prior art are excluded by the recitation of “consisting essentially of,” applicant has the burden of showing that the introduction of additional steps or components would materially change the characteristics of applicant's invention
New and Modified Objections/Rejections Necessitated by the Amendments filed October 20 2025
Claim Objections
Claim 6 is objected to because of the following informalities: the claim recites “at least at least 12” in lines 2-3. One of the “at least” recitations need to be deleted. Appropriate correction is required.
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 of this title, 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 35 U.S.C. 103 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 2-3, 5-9, 12-14, 16, 22-27, 29-31, 36-37, 46 and 56 are rejected under 35 U.S.C. 103 as being unpatentable over Lundberg et al. (WO2018002886, cited on PTO Form 1449).
Applicant Claims
The instant application claims an oligomeric compound comprising a modified oligonucleotide consisting of 12 to 50 linked nucleosides and having a nucleobase sequence comprising at least 12, at least 13, at least 14, at least 15, at least 16, at least 17, at least 18, at least 19, or 20 contiguous nucleobases of the nucleobase of SEQ ID NO: 149 or 150, wherein the modified oligonucleotide comprises at least one modification selected from a modified sugar moiety and a modified internucleoside linkage.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Lundberg et al. is directed to materials and methods for treatment of spinocerebellar ataxia 3 (SCA3) and other related disorders. Claimed is a single-molecule guide RNA comprising at least a spacer sequence that is an RNA sequence corresponding to any of SEQ ID Nos: 5305-56902 (claim 46). These sequences are 20 bp spacer sequences for targeting within or near a ATXN3 gene (paragraph 00056-00061). The single-molecule guide RNA is chemically modified (claim 49). Chemical modifications include one or more nucleotides modified at the 2’ position of the sugar, such as 2’-O-alkyl, 2’-fluoro modified nucleotide. Incorporation of these modifications have been shown to have higher target binding affinity (Tm) than 2’-deoxyoligonucleotides against a given target (paragraph 000164). Nucleotide and nucleoside modifications that have been shown to make the oligonucleotide into which they are incorporated more resistant to nuclease digestion than the native oligonucleotide. These include phosphorothioate, phosphodiester, phosphotriesters, short chain alkyl or cycloalkyl intersugar linkages, etc. Taught are peptide nucleic acid (PNA), morpholino-based oligomeric compounds, etc. (paragraph 000165-000166; 000168). Various sugar modifications such as OCH3 (OMe) and 2’-O-(2-methoxyethyl) (i.e. MOE) are taught (paragraph 000169). Modified nucleobases include 5-methylcytosine (paragraph 000172). These modified nucleobases have been shown to increase nucleic acid duplex stability and are aspects of base substitutions, even more particularly when combined with 2’-O-methoxyethyl sugar modifications (paragraph 000173). The guide RNAs can be chemically linked to one or more moieties or conjugates that enhance the activity, cellular disruption or cellular uptake of the oligonucleotide (paragraph 000175). Guide RNAs can be formulated with pharmaceutically acceptable excipients such as carriers, solvents, stabilizers, etc. depending on the particular mode of administration and dosage form. The composition can comprise a therapeutically effective amount of at least one compound as described herein, together with one or more pharmaceutically acceptable excipients. Examples include liquids such as saline (paragraph 000320-000321).
Specific Sequences taught include:
SEQ ID No: 49898 (Qy) which contains 18 contiguous nucleobases that are the same as SEQ ID No. 149 (Db).
PNG
media_image1.png
94
342
media_image1.png
Greyscale
SEQ ID No. 49898 (Qy) is 100% complementary to 42640-42659 of SEQ ID No. 2 (Db):
PNG
media_image2.png
76
390
media_image2.png
Greyscale
SEQ ID NO: 49902 (Qy) which contains 19 contiguous nucleobases that are the same as SEQ ID No. 150 (Db).
PNG
media_image3.png
100
384
media_image3.png
Greyscale
SEQ ID No. 49902 (Qy) is 100% complementary to 42625-42644 of SEQ ID No. 2 (Db):
PNG
media_image4.png
96
384
media_image4.png
Greyscale
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Lundberg et al. suggest oligonucleotides reading on the instantly claimed oligonucleotides and suggests that these nucleotides can be chemically modified, Lundberg et al. does not expressly teach the oligonucleotide comprises at least one modification selected from a modified surfer moiety and a modified internucleoside linkage. However, Lundberg et al. does suggest that chemical modifications can be modified sugars and/or internucleoside linkages.
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize a modified oligonucleotide. One skilled in the art would have been motivated to utilize a modified oligonucleotide in order to create an oligonucleotide with higher target binding affinity and an oligonucleotide that is more resistant to nuclease digestion as taught by Lundberg et al. One skilled in the art would have been motivated to utilize a sugar modification such as OMe, MOE, morpholino, PNA and/or use an internucleoside modification such as a phosphorothioate or phosphodiester as these are all chemical modifications which can be used as taught by Lundberg et al. One skilled in the art would manipulate the sequence with modifications in order to achieve the desired binding affinity and resistance. Therefore, all of the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. Note: MPEP 2143 KSR International Co. v. Teleflex Inc., 550 US 398, 82 USPQ 2d 1385 (2007). These modifications read on claims 2-3, 5, 7-9, 12-14 (at least one non-bicyclic modified sugar moiety; OMe, MOE), 16 (morpholino, PNA) and 22-27.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize a modified of 6-methyl cytosine. One skilled in the art would have been motivated to utilize this modification as it is a specific modification taught by Lundberg et al. One skilled in the art would have been motivated to utilize a modified nucleobase in order to increase stability as taught by Lundberg et al. One skilled in the art would have a reasonable expectation of success as Lundberg et al. teaches these base substitutions in combination with a 2’-O-methoxyethyl sugar modification. This renders obvious instant claims 29-30.
Regarding the claimed oligonucleotide, claims 2-3, 5, 7, 31, 36-37 and 46 as set forth above, SEQ ID No. 49898 and 49902 are 100% complementary to an equal length portion of an ATXN3 nucleic acid (i.e. SEQ ID No. 2). These sequences have 18 or 19 contiguous nucleobases that to SEQ ID No. 149 and 150 respectfully.
Regarding claim 6, as set forth above SEQ ID No. 49898 (Qy) is 100% complementary to 42640-42659 of SEQ ID No. 2 (Db). This results in at least 12 (specifically 18) contiguous nucleobases complementary to 42,626-42,657 of SEQ ID NO: 2. SEQ ID No. 49902 (Qy) is 100% complementary to 42625-42644 of SEQ ID No. 2 (Db). This results in at least 12 (specifically 19) contiguous nucleobases complementary to 42,626-42,657 of SEQ ID No: 2.
Regarding claim 56, Lundberg et al. teaches compositions comprising just the guide RNA and the carrier.
Claims 57-59 are rejected under 35 U.S.C. 103 as being unpatentable over Lundberg et al. as applied to claims 2-3, 5-9, 12-14, 16, 22-27, 29-31, 36-37, 46 and 56 above and in view of Cubillos-Ruiz et al. (USPGPUB No. 20160237429, cited in the Office Action mailed on 4/21/2025).
Applicant Claims
The instant application claims the diluent is artificial CSF or PBS.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
The teachings of Lundberg et al. are set forth above.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Lundberg et al. suggests a carrier which can be saline, Lundberg et al. does not expressly teach an artificial CSF or PBS. However, this deficiency is cured by Cubillos-Ruiz et al.
Cubillos-Ruiz et al. is directed to compounds for inducing anti-tumor immunity and methods thereof. Vehicles or carriers for pharmaceutical compositions can be either aqueous or non-aqueous in nature. Suitable vehicles or carrier can be water, physiological saline solution or artificial cerebrospinal fluid. The saline can be phosphate buffered saline (i.e. PBS) (paragraph 0209).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Lundberg et al. and Cubillos-Ruiz et al. and utilize either phosphate buffered saline or artificial cerebrospinal fluid as the carrier for the composition of Lundberg et al. It would have been obvious to one of ordinary skill in the art to choose known carriers for delivering the composition. Since Lundberg et al. suggest the carrier can be a saline there is a reasonable expectation of success. Therefore, all of the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. Note: MPEP 2143 KSR International Co. v. Teleflex Inc., 550 US 398, 82 USPQ 2d 1385 (2007).
Claims 10, 18-21, 28, 38-40, 43, 45, 57 and 59 are rejected under 35 U.S.C. 103 as being unpatentable over Lundberg et al. as applied to claims 2-3, 5-9, 12-14, 16, 22-27, 29-31, 36-37, 46 and 56 above and in view of Freier et al. (WO2018089805, cited in the Office Action mailed on 4/21/2025).
Applicant Claims
The instant application claims the modified oligonucleotide comprises at least one bicyclic sugar moiety.
The instant application claims the modified oligonucleotide has a sugar motif comprising:
a 5'-region consisting of 1-6 linked 5'-nucleosides, each comprising a 2'-MOE sugar moiety;
a 3'-region consisting of 1-5 linked 3'-nucleosides, each comprising a 2'-MOE sugar moiety;
and a central region consisting of 6-10 linked central region nucleosides,
wherein one of the central region nucleosides comprises a 2'-O-methyl sugar moiety and the remainder of the central region nucleosides each comprise a 2'-β-D-deoxyribosyl sugar moiety.
The instant application claims the central region has the following formula (5'-3'): (Nd)(Ny)(Nd)n, wherein Ny is a nucleoside comprising a 2'-O-methyl sugar moiety and each Na is a nucleoside comprising a 2'-β-D-deoxyribosyl sugar moiety, and n is 10.
The instant application claims the modified oligonucleotide comprises an internucleoside linkage motif (5' to 3') selected from among: sooooossssssssssoss, soooossssssssssooos, soooossssssssssooss, sooosssssssssooss, sooossssssssssooss, sooosssssssssssooos, sooosssssssssssooss, sossssssssssssssoss, and ssoosssssssssssooss; wherein, s is a phosphorothioate and o is a phosphodiester.
The instant application claims the oligomeric compound comprises a conjugate group comprising a conjugate moiety and a conjugate linker.
The instant application claims the oligomeric compound comprises a terminal group.
The instant application claims the diluent is PBS.
Although not expressly claimed, the elected species are associated with specific gapmers identified in the specification (page 65; SEQ ID No. 149 and 150) as follows:
PNG
media_image5.png
86
426
media_image5.png
Greyscale
SEQ ID No. 149
PNG
media_image6.png
88
434
media_image6.png
Greyscale
SEQ ID No. 150.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
The teachings of Lundberg et al. are set forth above.
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Lundberg et al. suggests a modified oligonucleotide and that the modification can be on the sugar moiety, Lundberg et al. does not expressly teach a bicyclic sugar moiety. While Lundberg et al. suggest phosphodiester or phosphorothioate, Lundberg et al. does not expressly teach the structural arrangement claimed. However, these deficiencies are cured by Freier et al.
Freier et al. is directed to compounds and methods for reducing ATXN3 expression. Taught are oligomeric compounds comprising a region that is complementary to a target nucleic acid wherein the target nucleic acid is ATXN3 (page 31). As claimed the oligonucleotides comprise modified sugar moieties that are bicyclic having a 2’-4’ bridge where the bridge is selected from O-CH2 and O-CH(CH3)- (claims 5-6). Non-bicyclic sugar moieties comprise 2’-MOE or 2’-OMe (claim 8). Modified nucleosides include a sugar surrogate such as morpholino and PNA (claims 9-10). The modified oligonucleotide has a sugar motif comprising a 5’-region consisting of 1-5 linked 5’-nucleosides; a central region consisting of 6-10 linked central region nucleosides and a 3’-region consisting of 1-5 linked 3’-region nucleosides wherein each of the 5-region nucleosides and each of the 3’-region nucleosides comprise a modified sugar moiety and each of the central region nucleosides comprise an unmodified DNA sugar moiety (claim 11). Modified internucleoside linkages include phosphorothioate and phosphodiesters (claims 14-15). Modified nucleobase of 5-methylcytosine is claimed (claim 18). A conjugate group comprising a conjugate moiety and a conjugate linker wherein the conjugate comprises a GalNAc cluster comprising 1-3 GalNAc ligands (claims 22-23). Conjugate groups modify one or more properties of the attached oligonucleotide (page 25) The conjugate linker consists of a single bond, is cleavable and comprises 1-3 linker nucleosides (claims 24-26). The conjugate is attached at the 5’-end of the modified oligonucleotide or at the 3’-end of the modified oligonucleotide (claims 27-28). The oligomeric compound comprises a terminal group (claim 29). Taught are composition comprising the oligomeric compound and a diluent or carrier. Diluents include PBS (page 33). Specific sequence motifs include es-eo-eo-eo-es-ds-ds-ds-ds-ds-ds-ds-ds-eo-eo-es-es-e wherein all C are MC (see table 1 starting on page 37). The internucleoside linkages are arranged in order from 5’ to 3’: sooosssssssssooss where o is phosphodiester and s is phosphorothioate (page 35). Gapmers include deoxy gapmers where on the gap side of each wing/gap junction are unmodified 2’-deoxynucleosides and the nucleosides on the wing sides of each wing/gap junction are modified nucleosides. Taught is that the sugar moieties of the wing are different than the sugar moieties of the gap. Gapmers include 5-10-5 gapmer with 5 linked MOE modified nucleosides in the 5’-wing, 10 linked deoxynucleosides in the gap and 5 linked MOE nucleosides in the 3’ wing (page 21). Gapmer motifs include 2’-deoxyribosyl moieties (page 22). The modified oligonucleotides of a chirally enriched population are enriched for β-D ribosyl sugar moieties (page 24).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Lundberg et al. and Freier et al. and utilize PBS. One skilled in the art would have been motivated to utilize PBS as it is a known diluent for forming compositions as taught by Freier et al. Since Lundberg et al. suggest the carrier can be saline there is a reasonable expectation of success.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Lundberg et al. and Freier et al. and utilize a bicyclic sugar moiety and the gapmer motif taught in Freier et al. One skilled in the art would have been motivated to utilize the bicyclic sugar moiety and gapmer motif known in the art to be used in designing gapmers which are designed to target ATXN3 similar to Lundberg et al. Since Lundberg et al. suggests using modified sugars to form oligonucleotides that target ATXN3 there is a reasonable expectation of success.
Regarding claim 10, Freier et al. claims that the bicyclic sugar moiety has a 4’-2’ bridge selected from O-CH2 and O-CH(CH3)-.
Regarding claims 18-21, Freier et al. teach the modified oligonucleotide has a sugar motif comprising a 5’-region consisting of 1-5 linked 5’-nucleosides; a central region consisting of 6-10 linked central region nucleosides and a 3’-region consisting of 1-5 linked 3’-region nucleosides wherein each of the 5-region nucleosides and each of the 3’-region nucleosides comprise a modified sugar moiety and each of the central region nucleosides comprise an unmodified DNA sugar moiety. Gapmers include 5-10-5 gapmer with 5 linked MOE modified nucleosides in the 5’-wing, 10 linked deoxynucleosides in the gap and 5 linked MOE nucleosides in the 3’ wing. Gapmer motifs include 2’-deoxyribosyl moieties. The modified oligonucleotides of a chirally enriched population are enriched for β-D ribosyl sugar moieties. This suggests the same motif instantly claimed.
Regarding claim 28, Frier et al. teaches the internucleoside linkages are arranged in order from 5’ to 3’: sooosssssssssooss where o is phosphodiester and s is phosphorothioate reading on the claim.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Lundberg et al. and Freier et al. and utilize a conjugate group. One skilled in the art would have been motivated to utilize a conjugate group in order to modify the properties of the oligonucleotide as taught by Freier et al. Since Lundberg et al. suggests conjugation there is ar reasonable expectation of success.
Regarding claim 38-40 and 43, Freier et al. claims the same conjugate group and location.
Regarding claim 45, Freier et al. suggest a terminal group which can be added for similar reasons to the conjugate group.
Therefore, a person of ordinary skill in the art would have had the technological capabilities to incorporate the motifs taught in Freier et al. as applied to gapmers that target ATXN3 to the oligonucleotides of Lundberg et al. which target ATXN3. One skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. Note: MPEP 2143 KSR International Co. v. Teleflex Inc., 550 US 398, 82 USPQ 2d 1385 (2007).
Regarding the specific structures of 149 and 150, Freier et al. teach gapmers with the following pattern: es-eo-eo-eo-es-ds-ds-ds-ds-ds-ds-ds-ds-eo-eo-es-es-e wherein all C are MC. Application of this motif to the sequences of Lundberg et al. which correspond to instantly claimed 149 and 150 would result in the exact same structure.
Response to Arguments
The examiner acknowledges the typo in the previous office action in which Lundberg is inadvertently referred to as Lundgren. However, the statement of rejection (page 15; 16) clearly indicated the rejection was over the reference applied to claims 1-2 above which was Lundberg). The typo has been corrected above.
Applicants’ arguments filed October 20 2025 have been fully considered but they are not persuasive.
Applicants argue (page 13) that (1) one of ordinary skill in the art, considering Lundberg, at the time of the present invention and without the benefit of hindsight would not have arrived at the specific compounds recited in the present. The rejection relies on impermissible hindsight using the present claims as a roadmap. It is argued that it is improper to combine reference without explaining what reason or motivation one of ordinary skill in the art would have had to assemble those pieces.
In response to applicant's argument that the examiner's conclusion of obviousness is based upon improper hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971). Here, firstly, Lundberg et al. expressly teaches and claims that the sequences are for targeting within or near a ATXN3 gene, which is the same target as the instant claims. Secondly, the sequences pointed to by the examiner are specifically claimed. Thirdly, Lundberg et al. teaches that the modification have been shown to have higher target binding affinity. The office action at pages 13-14 provides clear motivation for modifying the oligonucleotides specifically taught. Therefore, the examiner cannot agree that the rejection is based on hindsight or no motivation is provided to render the instant claims obvious.
Applicants argue (page 13) that (2) the cited sequences of Lundberg do not comprise at least 12 consecutive nucleobases of SEQ ID NO: 149 or 150 and complementary to an equal length portion of nucleobases 42626-42657 of SEQ ID No: 2 and at least one modification. It is argued that SEQ ID NO: 49898 and 49902 are not disclosed anywhere in the specification or figures. It is argued that Lundberg describes guide RNA and nowhere does the reference teach an antisense compound.
Regarding Applicants second argument, firstly, the examiner cannot agree that Lundberg do no teach oligonucleotides that comprise at least 12 consecutive nucleobases of SEQ ID NO 149 and 150. As set forth above and in the previous Office Action, SEQ ID No. 49898 and 49902 are 100% complementary to an equal length portion of an ATXN3 nucleic acid (i.e. SEQ ID No. 2) and these sequences have 18 or 19 contiguous nucleobases corresponding to that of SEQ ID No. 149 and 150 respectfully. These sequences are just not expressly taught as having a modification. While Applicants contend that SEQ ID No. 49898 and 49902 are only mentioned in the sequence listing, the examiner cannot agree. Lundberg et al. claims (claim 46) an RNA sequence corresponding to any of SEQ ID Nos: 5305-56902 which necessarily include 49898 and 49902 (see also paragraph 00029, 000105, 000376-000378, Table 6, 000380 and example 6). Paragraph 00061 states: SEQ ID NOs: 30886 - 56902 are 20 bp spacer sequences for targeting within or near a ATXN3 gene or other DNA sequence that encodes a regulatory element of the ATXN3 gene with an Acidaminococcus, a Lachnospiraceae, and a Franciscella Novicida Cpf 1 endonuclease. Thus, the examiner cannot agree that the sequences which render the instant claims obvious are not taught in the claims or specification. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., antisense compound) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). The instant claims are merely directed to an oligomeric compound corresponding to SEQ ID NO: 149 and 150. Therefore, as long as the prior art teaches the same sequence it teaches the same oligomeric compound. Furthermore, even if the claims recited an antisense compound, this recitation in and of itself does not distinguish the instantly claimed nucleotide sequence from the sequence recited in the prior art.
Applicants argue (page 14) that (4) nothing in Lundberg would have motivated one of ordinary skill in the art to specifically select SEQ ID No: 49898 or 49902 as starting sequences out of more than 50,000 sequences disclosed in Lundberg and modify it as recited in the instant claims to arrive at the claimed invention. Lundberg ultimately focuses on a selection of the most active compounds for in vitro testing but none of those are SEQ ID No: 49898 or 49902. Lundberg fails to provide any data or experimental evidence that the sequences can actually function as gRNA. One of ordinary skill in the art would not have any basis with any reasonable expectation of success to select SEQ ID No: 49898 or 49902.
Regarding Applicants’ fourth arguments, the rejection is made under 103 and does not need to exemplify all embodiments, only suggest. “Disclosed examples and preferred embodiments do not constitute a teaching away from the broader disclosure or non-preferred embodiment.” In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971). MPEP 2123. In order to render the instant claims obvious it is not necessary that the prior art teaches that SEQ ID No: 49898 or 49902 is the best option, only that it is a suitable option. Note: MPEP 2144.07. While there are numerous sequences taught, these are all taught for the same purpose, i.e. to target ATXN3. Therefore, Lundberg et al. teaches a finite list of sequences which can be used to target ATXN3 and applicants are merely claiming one of those sequences. None of the arguments presented establish an unexpected effect with the instantly claimed sequences. The instantly rejected claims are directed to an oligomeric compound, not the use of the compound. Based on the express teachings in Lundberg et al. it would be expected that the sequences claimed would target ATXN3. Furthermore, even if Lundberg et al. taught these sequences as less effective, wouldn’t this provide the motivation to modify the structure since Lundberg et al. expressly teaches the modification improve binding affinity. If targeting ATXN3 is desired, then the prior art itself suggests the reason to modify the sequences to improve binding affinity absent a demonstration of an unexpected effect.
Applicants argue (page 16) that (5) Lundberg fails to teach or would not have suggested the instantly claimed oligomeric compound. The examiner has provided no motivation to select either of SEQ ID NO: 49898 or 49902 as the starting sequence out of more than 50,000 gRNA. As in the InTouch Tech case there is no glue in Lundberg that could in any way teach or suggest putting the disparate teachings of Lundberg together in such a way as to lead to any of the instant claims.
Regarding Applicants’ fifth argument, as set forth above Lundberg expressly claims sequences which target ATXN3. Since targeting ATXN3 is a desire of Lundberg, the reference itself provides to motivation to select any of the specifically taught sequences. The difference between the instant claims and Lundberg is that Lundberg does not expressly teach the modifications associated with these sequences but Lundberg does teach that the modifications can be used with the oligonucleotides of the invention to improve target binding. This is neither impermissible hindsight or such an unreasonable interpretation of the prior art that one skilled in the art when reading Lundberg would not readily understand that the modifications can be applied to the claimed sequences. One skilled in the art would recognize the specific teachings in Lundberg of applying modifications to the claimed sequences. This is clearly motivation for making the modifications as set forth in the Office Action.
Applicants argue (pages 15-16) that (6) Cubillos-Ruiz fails to remedy the deficiencies of Lundberg.
Regarding Applicants’ sixth argument, the arguments are not persuasive for the reasons set forth above.
Applicants argue (16-17) that (7) Lundberg does not render claim 2 obvious for the reasons discussed above. Freier does not remedy the deficiencies of Lundberg.
Regarding Applicants’ seventh argument, the arguments are not persuasive for the reasons set forth above.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 ABIGAIL VANHORN whose telephone number is (571)270-3502. The examiner can normally be reached M-Th 6 am-4 pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached at 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ABIGAIL VANHORN/ Primary Examiner, Art Unit 1636