DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Applicant’s election without traverse of group I and the species SEQ ID NOs:233/370 and 235/372 in the reply filed on 3/3/26 is acknowledged. The sequences have been rejoined.
Claims 25-27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 3/3/26.
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 1-3, 10, 11, 14-16, and 19-22 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.
Claim 1 recites that the siRNA 3’ has two 3’ deoxythymidine overhangs. It is unclear whether this is intended to recite the siRNA “3’ ends” each have a 3’ deoxythymidine overhang or if the 3’ ends are each required to have two consecutive overhangs.
Claim 14 requires for the sense strand to comprise two 3’ deoxythymidine (should be plural deoxythymidines) and/or the antisense strand comprises two 3’ overhangs. This claim has an alternative wherein the antisense strand has two overhangs on the 3’ end, which is one of the possible interpretations for claim 1. It is unclear whether applicant intends for the one strand to have more than one 3’ overhang.
Claims 2, 3, 15, and 16 recite the limitation "the nucleotide sequence", although neither the claim or the independent claim recite a nucleotide sequence. There is insufficient antecedent basis for this limitation in the claim.
The claims that the sense strand or antisense strand comprise a nucleic acid sequence differing by no more than 3 or 2 nucleotides, respectively, from the nucleotide sequence. The independent claims do not recite a nucleotide sequence. Claims 2, 3, 15, and 16 recite a nucleic acid sequence, which is not identical to recitation of a nucleotide sequence. Assuming that the nucleotide sequence is referring to the nucleic acid sequence, it is not understood what is meant by the sense strand or antisense strand comprising a nucleic acid sequence that differs by no more than 3 or 2 nucleotides, respectively, from itself.
Should the language be referring to the nucleic acid sequences recited by SEQ ID NOs in the base claim, it is still unclear how the claims are further limiting because the base claims requires the entire sequence of the SEQ ID NO. The sequence cannot differ by no more than 2 or 3 nucleotides as recited.
Claim 10 requires for the siNA of claim 1 to comprise 5’ and/or 3’ overhangs. It is unclear how this is further limiting because claim 1 already requires for the “siRNA 3’” to have two 3’ deoxythymidine overhangs.
Claims 19 and 20 recite a molecule “described” in claim 1. This language is not definite and it is unclear whether the molecule of claim 1 is required. Recitation of “A vector comprising the molecule of claim 1” and “A liposome, microsphere, nanoparticle, or capsule comprising the molecule of claim 1”, for example, would obviate this part of the rejection.
Claim 21 recites a molecule “according to claim 1”, which is not definite. Recitation of “A pharmaceutical composition comprising the siNA of claim 1”, for example, would obviate this portion of the rejection.
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 14-16 and 22 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.
Claim 14 is directed to a dsRNA agent of any length (i.e. thousands of nucleotides) for inhibiting the expression of DBH, wherein the sense and antisense strands are one of the recited pairs of sequences within a double-stranded region of the dsRNA.
Claims 15 and 16 recite that the strands comprise (open language) a nucleic acid sequence differing by no more than 3 or 2 nucleotides, respectively, from the nucleotide sequence. Assuming that this is referring to the sequences recited by SEQ ID NO, this is only limiting to the sense and antisense strand, wherein the dsRNA comprises (open language) the strands and can comprise additional sequence, a genus of dsRNAs that has not been adequately described in the specification.
The species of the specification are not representative of the entire claimed genus. The specification does not adequately describe the structure required for the function.
Claim 22 recites that the ingredient is any “alpha adrenoceptor agonist”, any “beta adrenoceptor blocker”, any “carbonic anhydrase inhibitor”, any “muscarinic agonist”, any “prostaglandin analogue”, or any “rho kinase inhibitor”. The specification does not adequately describe the structure required for the ingredient to meet the limitation of being any “alpha adrenoceptor agonist”, any “beta adrenoceptor blocker”, any “carbonic anhydrase inhibitor”, any “muscarinic agonist”, any “prostaglandin analogue”, or any “rho kinase inhibitor”. The structure required for the function has not been adequately described. Without further description of the structure required for the function, one would not be able to readily envision which agents function as each of the recited genuses.
The MPEP states that for a generic claim, the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. See 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 species, the courts have indicated what do not constitute a representative number of species to adequately describe a broad genus. In Gostelli, the courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618. Additionally, in Carnegie Mellon University v. Hoffman-La Roche Inc., Nos. 07-1266, -1267 (Fed. Cir. Sept. 8, 2008), the Federal Circuit affirmed that a claim to a genus described in functional terms was not supported by the specification’s disclosure of species that were not representative of the entire genus. Furthermore, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. 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 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (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 Guidelines for Examination of Patent Applications under the 35 USC § 112, first paragraph, “Written Description” Requirement”, published at Federal Register, Vol. 66, No. 4, pp. 1099-1111 outline the method of analysis of claims to determine whether adequate written description is present. The first step is to determine what the claim as a whole covers, i.e., discussion of the full scope of the claim. Second, the application should be fully reviewed to understand how applicant provides support for the claimed invention including each element and/or step, i.e., compare the scope of the claim with the scope of the description. Third, determine whether the applicant was in possession of the claimed invention as a whole at the time of filing.
To achieve the desired function, it appears that the structure is required to be a duplex that is fully complementary to a target sequence and to be of shorter length than any dsRNA. With respect to siRNAs, a single species of dsRNA agents, Elbashir et al. (The EMBO Journal, Vol. 20, No. 23, pages 6877-6888, 2001) teaches that duplexes of 21-23 nt RNAs are the sequence specific mediators of RNAi and that even single mismatches between the siRNA duplex and the target mRNA abolish interference (abstract and page 6888).
The claims encompass very long dsRNA, for example, that can trigger RNAi. Such dsRNA with 14 contiguous nucleotides of any of the instantly recited sequences would not likely function as claimed. For example, Parrish et al. (Molecular Cell, Vol. 6, 1077–1087, November 2000) teach that sequences of 1000 bp trigger RNAi (page 1078).
Thus, having analyzed the claims with regard to the Written Description guidelines, it is clear that the specification does not disclose a representative number of species for dsRNA within the instant enormous genus that are inhibitory of the target as claimed; or agents that have the structure to function as any “alpha adrenoceptor agonist”, any “beta adrenoceptor blocker”, any “carbonic anhydrase inhibitor”, any “muscarinic agonist”, any “prostaglandin analogue”, or any “rho kinase inhibitor”. Thus, one skilled in the art would be led to conclude that Applicant was not in possession of the claimed invention at the time the application was filed.
Response to Arguments
Applicant argues that the claim has been amended to recite specific pairs of sequences. However, the claim language is directed to dsRNA, rather than siRNA, and do not recite a length limitation, wherein the dsRNA comprises (open language) the much shorter sequences.
Note
It is noted that the prior art rejections have been withdrawn because the amended claims require for the siRNA or the dsRNA to comprise the recited sequences and therefore require the entirety of the recited sequences. The instant claims are compound claims, not method claims. There was clearly motivation in the art to incorporation dTdT overhangs into siRNAs and the motivation does not need to be identical to that of applicant.
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 Amy R Hudson whose telephone number is (571)272-0755. The examiner can normally be reached M-F 8:00am-6:00pm.
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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.
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/AMY ROSE HUDSON/Primary Examiner, Art Unit 1636
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