DETAILED ACTION
This Action is in response to the amendment filed on 11/04/2025.
Claims 137-149 are pending.
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 .
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.
Claims 145-148 are 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.
Although the claims are identified as “(Previously Presented)” they has been changed as follows: Claims 145-146 “(SEQ ID NO: 208)” has been replaced with “(SEQ ID NO: 3007)”, and claims 147-148 “(SEQ ID NO: 286)” has been replaced with “(SEQ ID NO: 2990).” It is noted that SEQ ID NO: 2990 and SEQ ID NO: 3007 are not included in the Sequence Listing (which only includes SEQ ID NOs: 1-2989). Therefore, the claims are indefinite.
It is noted that should Applicant wish to add SEQ ID NOs: 2990 and 3007 to this application, an amended sequence listing in compliance with the sequence rules is required. It is noted that this appears to be a typographical error where claims 145-148 were not intended to be amended (as they are identified as “Previously Present”). However, the change to the claims necessitates the instant rejection and since it is impossible to search for sequences not present in the sequence listing (SEQ ID NOs: 2990, 3007) the claim have not been further examined.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 137, 149 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO2017141109 (hereafter “Zhang”).
Regarding claims 137 and 149, Zhang teaches a compound comprising a modified oligonucleotide consisting of 20 linked nucleotides with 16 contiguous nucleobases 100% complementary to an equal length portion of nucleobases 6422-6493 of SEQ ID NO: 2 and wherein the modified oligonucleotide is at least 85% complementary to SEQ ID NO: 2 (see sequence alignment information below where Zhang’s SEQ ID NO: 62529 is 20 nucleotides in length and has 18 of 20 nucleotides complementary to 6422-6493 of SEQ ID NO: 2 with 16 contiguous nts 100% complementary). Also see paragraph [0065].
SEQUENCE ALIGNMENT INFORMATION
CC PN WO2017141109-A1.
XX
CC PD 24-AUG-2017.
XX
CC PF 17-FEB-2017; 2017WO-IB000200.
XX
PR 18-FEB-2016; 2016US-0296842P.
PR 18-APR-2016; 2016US-0323843P.
XX
CC PA (CRIS-) CRISPR THERAPEUTICS AG.
XX
CC PI Zhang Y, Cowan CA, Lundberg AS, Cost GJ;
XX
DR WPI; 2017-57949W/61.
XX
CC PS Claim 75; SEQ ID NO 62529; 168pp; English.
XX
CC SEQ ID 1-54,859 (BEF88839-BEG43698) represent
CC gRNA spacer sequences for editing the safer harbour locus in a cell from
CC a patient with SCID or Omenn syndrome, and SEQ ID 54,862-63,375 (BEG43701
CC -BEG52212) represent gRNA spacer sequences for editing the IL7R gene in a
CC cell from a patient with SCID or Omenn syndrome.
Length 20;
Matches 18; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 34 GAATTACTACTTAGCACTT 52 (from nts 6422-6493 of SEQ ID NO: 2)
|||||||||||||||| ||
Db 20 GAATTACTACTTAGCAATT 2 (Zhang’s SEQ ID NO 62529)
Claims 137, 139-144, 149 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by US20210155935A1 (hereafter “Jo”).
Regarding claims 137 and 149, Jo teaches a compound comprising a modified oligonucleotide consisting of 16 linked nucleotides with 14 contiguous nucleobases 100% complementary to an equal length portion of nucleobases 6422-6493 of SEQ ID NO: 2 and wherein the modified oligonucleotide is at least 85% complementary to SEQ ID NO: 2 (see sequence alignment information below where Jo’s SEQ ID NO: 564 is 16 nucleotides in length and has 14 of 16 nucleotides complementary to 6422-6493 of SEQ ID NO: 2 with 14 contiguous nts 100% complementary). Jo also explicitly teaches that the oligonucleotide can comprise different modifications (e.g., see [0127]-[0130]).
Regarding claim 139, Jo teaches the modified oligonucleotide comprises: a gap segment consisting of linked 2'-deoxynucleosides; a 5' wing segment consisting of linked nucleosides; and a 3' wing segment consisting of linked nucleosides; wherein the gap segment is positioned between the 5' wing segment and the 3' wing segment and wherein each nucleoside of each wing segment comprises a modified sugar (e.g., see [0131]-[0132]).
Regarding claim 140, Jo teaches the modified oligonucleotide comprises: a gap segment consisting of ten linked 2'-deoxynucleosides; a 5' wing segment consisting of three linked nucleosides; and a 3' wing segment consisting of three linked nucleosides; wherein the gap segment is positioned between the 5' wing segment and the 3' wing segment; wherein each nucleoside of each wing segment comprises a cEt nucleoside; wherein each internucleoside linkage is a phosphorothioate linkage; and wherein each cytosine is 5- methylcytosine (e.g., see [0146]-[0150]).
Regarding claims 141-144, Jo teaches that the modified oligonucleotide can comprise a conjugate group, wherein the conjugate group is a GalNAc cluster, wherein the conjugate group is attached to the 5’-end and/or the 3’-end of the oligonucleotide (e.g., see [0432], [0437], etc.).
SEQUENCE ALIGNMENT INFORMATION:
Publication No. US20210155935A1
GENERAL INFORMATION
APPLICANT: Ionis Pharmaceuticals, Inc.
TITLE OF INVENTION: MODULATORS OF EZH2 EXPRESSION
FILE REFERENCE: BIOL0334USA
CURRENT APPLICATION NUMBER: US/17/045,426
CURRENT FILING DATE: 2020-10-05
PRIOR APPLICATION NUMBER: PCT/US2019/027090
PRIOR FILING DATE: 2019-04-11
PRIOR APPLICATION NUMBER: 62/656,244
PRIOR FILING DATE: 2018-04-11
NUMBER OF SEQ ID NOS: 1592
SEQ ID NO 564
LENGTH: 16
TYPE: DNA
ORGANISM: Artificial sequence
FEATURE:
OTHER INFORMATION: Synthetic oligonucleotide
Length 16;
Best Local Similarity 100.0%;
Matches 14; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 5 GCATACAGTTTACC 18 (from nts 6422-6493 of SEQ ID NO: 2)
||||||||||||||
Db 14 GCATACAGTTTACC 1 (Jo’s SEQ ID NO: 564)
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 137, 139-144 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117.
To satisfy the written description requirement, MPEP §2163 states, in part “…a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention.” Moreover, the written description requirement for a genus may be satisfied through sufficient description of a representative number of species by “…disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between functional and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.”
The claims are drawn to a compound comprising a modified oligonucleotide consisting of 14 to 30 linked nucleosides, wherein the modified oligonucleotide has a nucleobase sequence comprising a portion of at least 14 contiguous nucleobases 100% complementary to an equal length portion of nucleobases 6422-6493 of SEQ ID NO: 2, and wherein the nucleobase sequence of the modified oligonucleotide is at least 85% complementary to SEQ ID NO: 2. (See claim 137).
Accordingly, the claims encompass a genus of different oligonucleotides that can vary in size from 14 to 30 nucleosides, wherein the oligonucleotide can have as few as 14 contiguous nucleobases 100% complementary the target sequence of SEQ ID NO: 2, wherein the oligonucleotide must be at least 85% complementary to SEQ ID NO: 2. Considering every possible oligonucleotide that meets the broad structural limitations of the claims, the claims encompass a very large number of different oligonucleotides.
The application only appears to disclose functional oligonucleotides that consist of 16 linked nucleosides (e.g., see Table provided in Applicant’s arguments which includes SEQ ID NO: 208 and SEQ ID NO: 286, as well as other sequences taken from Tables 1-38). It is noted that there does not appear to be any core sequence structure common to the oligonucleotides. Furthermore the specification does not appear to disclose any other oligonucleotides, such as oligonucleotides 14, 15, or 17-30 nucleotides in length which have 14 contiguous nucleobases 100% complementary the target sequence and wherein the oligonucleotide is 85% complementary to SEQ ID NO: 2 and inhibits HSD17B13 expression. That is the specification does not disclose which variations of the disclosed oligonucleotides that meet the structural limitations of the claims (14 contiguous nucleosides 100% complementary wherein the oligonucleotide is at least 85% but less than 100% complementary to target sequence) would be functional and which ones would not. Accordingly, additional experimentation would be required to determine which oligonucleotides encompassed by the claims, other than the specifically disclosed oligonucleotides, which includes SEQ ID NO: 208 and 286, are functional. Therefore, the limited disclosure of the specification in view of the large genus of molecules encompassed by the claims does not adequately describe the entire genus of molecules encompassed by the claims
“Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features.” Ex parte Kubin, 83 USPQ2d 1410, 1417 (Bd. Pat. App. & Int. 2007) citing University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
In Regents of the University of California v. Eli Lilly & Co., the court stated:
“A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials. Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284-85 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus. . . ."). Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gosteli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. (Emphasis added). In re Gosteli, 872 F.2d at 1012, 10 USPQ2d at 1618.
The court and the Board have repeatedly held (Amgen Inc. v. Chugai Pharmaceutical Co. Ltd.,18 USPQ2d 1016 (CA FC, 1991); Fiers v. Revel, 25 USPQ2d 1601 (CA FC 1993); Fiddes v. Baird, 30 USPQ2d 1481 (BPAI 1993) and Regents of the Univ. Calif. v. Eli Lilly & Co., 43 USPQ2d 1398 (CA FC, 1997)) that an adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it, irrespective of the complexity or simplicity of the method; what is required is a description of the nucleic acid itself.
The specification does not provides sufficient description or guidance that would allow one of skill to distinguish the functional oligonucleotide species of the recited structural genus from the non-functional members without empirical determination. Thus one of skill at the time of the invention could not have concluded that Applicant was in possession of the genus of functional inhibitory oligonucleotides that is required to practice any of the claimed methods.
It is noted that limiting the claims to an oligonucleotide that is SEQ ID NO: 208, SEQ ID NO: 286 or any of the other explicitly disclosed functional oligonucleotides would obviate this rejection.
Claim Objections
Claim 138 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. The instant claims are otherwise allowable as the prior art does not teach the claimed oligonucleotide having SEQ ID NO: 208 or SEQ ID NO: 286.
Response to Arguments
Regarding the rejection of claims under 35 USC 102 set forth in the previous Office action, Applicant’s arguments have been fully considered and in view of the amendment to the claims are persuasive. The rejection has been withdrawn. However, upon consideration of the amended claim, a new grounds of rejection is set forth for the reasons indicated above. The new rejection is necessitated by the amendment to the claims.
It is noted that a new rejection under 35 USC 112(b) has been set forth for the reasons indicated above. The new rejection is necessitated by the amendment to the claims 145-148 as indicated in the rejection.
With respect to the rejection under 35 USC 112(a) (written description) Applicant's arguments have been fully considered but they are not persuasive. Applicant argues that numerous oligonucleotides which meet the structural limitations and have the required function are disclosed, providing a Table listing the oligonucleotides.
Applicant’s arguments are not persuasive because the disclosed functional oligonucleotides are all oligonucleotides that consist of 16 linked nucleosides that are 100% complementary to the target site of SEQ ID NO: 2, while that claims encompass oligonucleotides that are 14 to 30 nucleotides in length with at least 14 contiguous nucleobases 100% complementary to an equal length portion of nucleobases 6422-6493 of SEQ ID NO: 2, and wherein the nucleobase sequence of the modified oligonucleotide is at least 85% complementary to SEQ ID NO: 2. As indicated in the rejection, it does not appear that there is any core structure common to all members of the genus of oligonucleotides encompassed by the claim. Furthermore, there does no appear to be any guidance indicating which oligonucleotides which meet the broad structural limitations of the claims but which do not consist of 16 linked nucleotides 100% complementary to the target region of SEQ ID NO: 2 are functional and which are not. Therefore, further experimentation would be required to identify the other (non-disclosed) functional oligonucleotides which meet the broad structural limitations. Accordingly Applicant’s arguments are not persuasive. It is noted amending the claims to any of the explicitly disclosed functional oligonucleotides, such as SEQ ID NO: 208 and SEQ ID NO: 286, would obviate this rejection.
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 J. E. Angell whose telephone number is (571)272-0756. The examiner can normally be reached Monday-Friday (8:30-5:00).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jennifer Dunston can be reached at (571) 272-2916. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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J. E. Angell
Primary Examiner
Art Unit 1637
/J. E. ANGELL/ Primary Examiner, Art Unit 1637