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, SEQ ID NOs: 126 and 300, in the reply filed on 8/8/25 is acknowledged.
Claims 18, 22-25, 32, 33, 43, 48, 52, and 56-64 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 8/8/25.
Applicant argues that claims 56-64 should not be withdrawn because the recited sequences are modified versions of the elected sequences. However, in applicant’s response filed on 8/8/25, applicant elected the species of SEQ ID NOs: 126 and 300, not one of the other duplexes with a specific modification pattern. Upon allowability of the elected form of the sequences, the species would be rejoined.
Claim Rejections - 35 USC § 112
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.
Claim 40 is 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 40 requires for the expression vector to further comprise any nucleotide sequence encoding any C3 inhibitor. The specification does not adequately describe the structure required for this function. Without further description of the genus, one would not be able to readily recognize which sequences encoding which agents with which structures acting on which targets would result in C3 inhibition.
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 claims are rejected under the written description requirement for failing to disclose adequate species to represent each of the claimed genuses.
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.
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 within the recited genus that would have the required function. 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 did not respond to this portion of the rejection.
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 following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries 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.
Claim(s) 2-4, 11-15, 19-21, 38-40, 65, and 66 is/are rejected under 35 U.S.C. 103 as being unpatentable over Keating et al. (US 12,365,896 B2), in view of Chiu et al. (WO 2007/124452 A2).
Keating et al. teach a siRNA comprising a sense strand and an antisense strand, wherein each strand is 23 nucleotides in length, wherein the antisense strand comprises a nucleotide sequence of 19 nucleotides that is 100% identical to instant SEQ ID NO: 300 (see column 154, AD572039.1) The antisense strand of Keating et al. comprises a nucleotide sequence of 19 nucleotides that differs by 0 nucleotides (instant claims 2 and 4). It is noted that Keating et al. has support for the siRNA in 62/924,210, filed 10/22/19 (see Table 4, AD572039.1).
Instant SEQ ID NO: 300 has the addition of UC at the 3’ end to the sequence of Keating et al. The sequence of Keating et al. has an additional 4 nucleotides at the 5’ end (AGAA). However, Keating et al. teaches that the siRNAs are 19-25 in length (column 4). Design of the specific sequence of Keating et al. in the size range taught by Keating et al. would result in a sequence 100% identical to nucleotides 1-19 of instant SEQ ID NO: 300. Design of the specific sequence of Keating et al. as a 20-mer antisense strand as instantly recited would result in a sequence 100% identical to nucleotides 1-19 of instant SEQ ID NO: 300 with one additional nucleotide at the 5’ end, differing from the instant sequence by 1 nucleotide. It would have been obvious to design the siRNA of Keating et al. within the size range taught by Keating et al. as a matter of design choice. Applicant has not demonstrated any unexpected property for the instantly recited genus of siRNAs of varying length possibilities and differing from the recited sequences by 1-3 nucleotides (instant claims 2, 65, and 66).
The sense strand of Keating et al. comprises a nucleotide sequence of 19 nucleotides (23 nucleotides total) that is 100% identical to SEQ ID NO: 126 (see nucleotides 1-19 of SEQ ID NO: 1043, mRNA target sequence of the siRNA). SEQ ID NO: 1043 of Keating et al. comprises instant SEQ ID NO: 126 (instant claim 3).
See the PE2E sequence search result (us-17-798-339-300.szlim50.rni) as follows:
RESULT 4
US-17-721-530-1115
Sequence 1115, US/17721530
Patent No. 12365896
GENERAL INFORMATION
APPLICANT: ALNYLAM PHARMACEUTICALS, INC.
TITLE OF INVENTION: COMPLEMENT COMPONENT C3 IRNA COMPOSITIONS AND METHODS OF USE
TITLE OF INVENTION: THEREOF
FILE REFERENCE: 121301-10502
CURRENT APPLICATION NUMBER: US/17/721,530
CURRENT FILING DATE: 2022-04-15
PRIOR APPLICATION NUMBER: PCT/US2020/056563
PRIOR FILING DATE: 2020-10-21
PRIOR APPLICATION NUMBER: 62/924,210
PRIOR FILING DATE: 2019-10-22
NUMBER OF SEQ ID NOS: 4652
SEQ ID NO 1115
LENGTH: 23
Query Match 90.5%; Score 19; Length 23;
Best Local Similarity 100.0%;
Matches 19; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 UUUAUUACAGGUGAGUUGA 19
Db 5 UUUAUUACAGGUGAGUUGA 23
Keating et al. teach that at least one strand comprises a 3′ overhang of at least 1 nucleotide. In another embodiment, at least one strand comprises a 3′ overhang of at least 2 nucleotides (column 4). Keating et al. teaches that the overhang can form a mismatch with the target mRNA or it can be complementary to the gene sequences being targeted or can be another sequence (column 31).
Keating et al. teaches that in one embodiment, each residue of the sense strand and antisense strand is independently modified with LNA, CRN, cET, UNA, HNA, CeNA, 2′-methoxyethyl, 2′-O-methyl, 2′-O-allyl, 2′-C-allyl, 2′-deoxy, 2′-hydroxyl, or 2′-fluoro. The strands can contain more than one modification. In one embodiment, each residue of the sense strand and antisense strand is independently modified with 2′-O-methyl or 2′-fluoro (column 35) (instant claims 11 and 12).
Keating et al. teaches incorporation of phosphorothioate modifications and teaches incorporation of two phosphorothioate internucleotide linkage modifications within position 1-5 of the sense strand (counting from the 5′-end of the sense strand), and two phosphorothioate internucleotide linkage modifications at positions 1 and 2 and two phosphorothioate internucleotide linkage modifications within positions 18-23 of the antisense strand (counting from the 5′-end of the antisense strand) (columns 52-53) (instant claim 13).
Keating et al. teaches that every nucleotide can comprise a phosphorothioate group (columns 3-4) which anticipates each of the quantities and positions required in instant claims 13-15.
Keating et al. teaches that the dsRNA agent further comprises a ligand. In one embodiment, the ligand is conjugated to the 3′ end of the sense strand of the dsRNA agent (instant claim 19). In one embodiment, the ligand is an N-acetylgalactosamine (GalNAc) derivative. In one embodiment, the ligand is one or more GalNAc derivatives attached through a monovalent, bivalent, or trivalent branched linker (column 4). Keating et al. teaches that the sense strand is conjugated to one or more GalNAc derivatives attached through a bivalent or trivalent branched linker (column 42) (instant claim 20).
Keating et al. teaches that in a particular embodiment, an RNAi agent of the present invention comprises: a sense strand having an ASGPR ligand attached to the 3′-end, wherein said ASGPR ligand comprises three GalNAc derivatives attached through a trivalent branched linker (column 61) (instant claim 21).
Keating et al. teach incorporation of the siRNA into a composition comprising a pharmaceutically acceptable carrier (column 20) (instant claim 38).
Keating et al. teach that in vivo delivery may be performed indirectly by administering one or more vectors that encode and direct the expression of the iRNA (column 100) (instant claim 39).
Keating et al. teach that an additional therapeutic agent for inhibition of C3 and that the agent can be delivered in the same composition (column 114). Keating et al. teach that the agent can be an RNAi agent targeting C3 (column 117) (instant claim 40). It would have been obvious to deliver the two agents from the same vector as a matter of design choice when delivering two siRNAs simultaneously.
For example, Chiu et al. teach (2007) methods and vectors for the expression of multiple siRNAs of different target sites or the same site of any gene simultaneously from a single vector, both viral and non-viral (abstract).
Keating et al. does not teach that the antisense strand comprises instant SEQ ID NO: 300 as required by instant claim 4.
However, the siRNA of Keating et al. targets the same region and Keating et al. teach that the siRNAs are 19-25 in length (column 4). Therefore, it would have been obvious to alter the length of the siRNA of Keating et al.; or to shift by two nucleotides; or extend the length by two nucleotides within the length range taught by Keating et al. and result in an antisense strand that comprises instant SEQ ID NO: 300. Applicant has not demonstrated any unexpected property for the instantly recited genus of siRNAs of varying length possibilities and differing from the recited sequences by 1-3 nucleotides, wherein clearly the target region was known.
Response to Arguments
Applicant argues that there is no motivation provided by Keating or Chui to modify the teachings of Keating to arrive at siRNAs of the present claims. Indeed, such modifications would require an alteration of several nucleotides in the sequences disclosed in Keating. The Office Action acknowledged that "Keating et al. does not teach that the antisense strand comprises instant SEQ ID NO: 300 as required by instant claim 4," but alleges that "it would have been obvious to shift by two nucleotides or extend the length by two nucleotides within the length range taught by Keating et al. and result in an antisense strand that comprises instant SEQ ID NO: 300" (Office Action, p. 17).
Applicant argues that there is nothing in Keating or Chui that teaches or suggests a specific modification that would lead to the specific siRNAs of the present claims, nor that would provide a reasonable expectation that such a modification could result in activity demonstrated by the present application.
Contrary to applicant’s arguments, it would have certainly been obvious in view of Keating et al. alone to design the siRNAs of Keating et al. within the size range taught by Keating et al. Keating et al. clearly taught the size range as the acceptable size range for the siRNAs. Altering the size of the antisense strand of the siRNA of Keating et al. to 20 nucleotides, which is in the size range taught by Keating et al., would result in a siRNA that anticipates instant claim 2.
Contrary to applicant’s arguments, the specification does not demonstrate any unexpected property for the instant genus of siRNAs. The claims are not closed to any specific siRNA that applicant has demonstrated any unexpected result for. The claims are directed to a genus of siRNAs wherein each strand can have different lengths and differences in sequence from the recited sequences. The siRNA of Keating et al. and the obvious alterations to the siRNA of Keating et al. in view of the teachings of Keating et al. render the instant genus obvious.
Applicant argues that the Office Action is also of the position that modifying sequences of a sense strand and/or antisense strand of an siRNA was not routine and may affect function (see Office Action, p. 6). The basis of this assertion is unclear because the statement made by the examiner at page 6 is directed to mismatches. The reference may in fact question the enablement of the activity of the instantly recited genus, which encompasses mismatches, but does not negate the argument which is in respect to the recited claim language.
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.
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.
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/AMY ROSE HUDSON/Primary Examiner, Art Unit 1636