DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of Group I, An is a low molecular weight organic compound, Sp is a bond,
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in the reply filed on April 28 2026 is acknowledged. Applicants additionally elected a particular sequence for E and X as well as F and Y. This specifically elected sequence is free of prior art. In light of the discovered prior art, the species election requirement for this portion of formula II is withdrawn. However, the species election for the rest of the molecule is maintained. Claims 8-11, 17, 19, 24, 36, 50, 55, 60-61, 70, 81-84, 96 and 100 are pending in the application. Claims 19, 82-83 and 100 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and species, there being no allowable generic or linking claim. The examiner notes that Applicants indicate that claims 19 and 82-83 read on the elected species, however, this is not correct. As elected LP1 and Lp2 are not present (in light of the election of p=0 and q=0) thus claim 19 does not read on the elected species. As elected Sp is a bond, thus claims 82-83 which recites Sp as a bifunctional spacer does not read on the elected species. Election was made without traverse in the reply filed on April 28 2026. Accordingly, claims 8-11, 17, 24, 36, 50, 55, 60-61, 70, 81, 84 and 96 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 .
Priority
This application is a 371 of PCT/JP2021/019685 (05/24/2021) which claims FOR priority to JAPAN 2020-090304 (05/25/2020) as reflected in the filing receipt issued on June 12 2023.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on November 25 2022, August 1 2023 and June 10 2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 112-Indefiniteness
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 9-10 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 9 recites the limitation "the double-stranded oligonucleotide tag”" in line 6. There is insufficient antecedent basis for this limitation in the claim. Firstly, claim 9 does not include a previous recitation of tag. Secondly, claim 8 refers to a duplex formed by oligonucleotide chain X and Y but never refers to a tag. The recitation duplex and tag do not appear to be of the exact same scope. Therefore, the recitation lacks antecedent basis.
Claim 10 lacks antecedent basis for the same reason as claim 9. Claim 10 depends from claim 8 and refers to the double-stranded oligonucleotide tag in lines 3-4. As set forth above claim 8 fails to provide antecedent basis for this recitation.
Claim Rejections - 35 USC § 112-Failure to further limit
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 84 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 84 recites chain X and Y are sequences capable of forming a duplex. This claim depends from claim 8. Claim 8 already recites this limitation in the 4th from last line of the claim.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 8-11, 17, 24, 36, 50, 55, 60-61, 70, 81, 84 and 96 are rejected under 35 U.S.C. 103 as being unpatentable over Iriyama et al. (WO2018143475, cited on PTO Form 1449) in view of Cook et al. (WO 2004037907).
Applicant Claims
Claimed is a compound represented by formula (II)
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wherein X and Y are oligonucleotide chains, E and F are each independently an oligomer constituted by nucleotides or nucleic acid analogues, provided that E and F contain base sequences, which are complementary to each other and form a duplex oligonucleotide, LP is a loop site, L is a linker and D is a divalent group derived from a reactive functional group, Sp is a bonding or a bifunctional spacer and An is a partial structure constituted by at least one building block, X and Y have a sequence capable of forming a duplex at least a part thereof, X binds to E at the 5' terminal end, Y binds to F at the 3' terminal end and has at least one selectively cleavable site at any of at least one site of E, F and LP.
As elected LP is
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;
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and D is amino.
Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Iriyama et al. (wherein USPGPUB No. 20210254055 is serving as the English language equivalent) is directed to single-stranded oligonucleotide. Claimed is a single stranded oligonucleotide represented by formula I:
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Wherein a specific configuration is shown in Figure 10:
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. X is a first oligonucleotide, Y is a second oligonucleotide, Xz represents a third oligonucleotide and Yz represents a fourth oligonucleotide. L is a linking group which can be of the formula P5-W5-P5 wherein P5 can be a -P(O)OH- and W is a fifth oligonucleotide composed of 1 to 50 nucleotides that include deoxyribonucleotides, ribonucleotides and sugar-modified nucleotides, Lx is a linking group which can include a -P(O)OH, a non-nucleotide structure or P6-W6-P6- wherein W6 is a sixth oligonucleotide; L7 is -P(O)OH, a non-nucleotide structure or P7-W7-P7- wherein W6 is a sixth oligonucleotide; wherein at least one of L, Lx and Ly is a linking group containing a non-nucleotide structure. L is covalently bonded with the first and second oligonucleotide at both ends wherein nucleotide sequence X is capable of hybridizing with at least a portion of Y (claim 1). In Fig. 16 A is in the form of a group derived from a functional molecule bonded to B and B can be an alkylene group (paragraph 1257). B is also taught as representing a C2-20 alkylene group or a C2-20 alkenylene group, the methylene groups contained in the alkylene group and the alkenylene group are respectively and independently unsubstituted, or substituted with one or more substituents selected from the group consisting of a halogen atom, a hydroxyl group, a protected hydroxyl group, an oxo group and a thioxo group. In addition, the methylene groups of the alkylene group and the alkenylene group are respectively and independently not replaced, or replaced with —O—, —NRB—(RB represents a hydrogen atom, a C1-6 alkyl group or a halo-C1-6 alkyl group), —S—, —S(═O)— or —S(═O)2— (paragraph 0844). As claimed the second nucleotide is a sequence that contains at least four contiguous nucleotides cleaved by RNase H (claim 13). Functional molecules include those having a labeling function, a purifying function and a target site delivery function (paragraph 0101). Nucleotides include 5-methylcytosine (paragraph 0184; 1238; 1306).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Iriyama et al. suggest a linking group which can form a loop (as illustrated in Fig. 10) which is connected via another linker to a group derived from a functional molecule, Iriyama et al. does not expressly teach the elected LP, L and D. However, this deficiency is cured by Cook et al.
Cook et al. is directed to luminescent metal ion complexes. Taught is a new class of versatile and cost effective luminescent metal ion complexes which are useful in detection and isolation of target analytes such as biomolecules (paragraph 0015). In one embodiment taught is a nucleic acid metal ion coordinating component that has the formula:
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(paragraph 0142) wherein R13 can be OR14 wherein R14 can be a H, phosphate, etc. (paragraph 0139); t and n represent integers from 0 to 10 and m is an integer from 1 to 10 wherein a narrower embodiment is t and n are from 0 to 5 and m is from 1 to 5 (paragraph 0137); R9 is hydrogen, nucleobase, oligonucleotide, etc. (paragraph 0129) or an oligonucleotide containing 1 to 50 nucleobases (paragraph 0131); R10 is H or OH (paragraph 0133); B is guanine, thymine, cytosine adenine or uracil (paragraph 0133) or generally a nitrogenous base (paragraph 0129); R4/R5/R6 are H (paragraph 0115). Nitrogenous bases include 5-methylcytosine (paragraph 0123). The luminescent metal ion complexes are capable of emitting light and have relatively high fluorescence detectability (paragraph 0146).
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 one of ordinary skill in the art to combine the teachings of Iriyama et al. and Cook et al. and utilize the compound VIII of Cook et al. as L-B-A in the oligonucleotide of Iriyama et al. One skilled in the art would have been motivated to utilize the compound of Cook et al. as Iriyama et al. teaches that L-B-A wherein L is a linking group which can be of the formula P5-W5-P5 wherein P5 can be a -P(O)OH- and W is a fifth oligonucleotide composed of 1 to 50 nucleotides that include deoxyribonucleotides, ribonucleotides and sugar-modified nucleotides, A is in the form of a group derived from a functional molecule bonded to B and B can be an alkylene group which can be unsubstituted or substituted wherein in addition, the methylene groups of the alkylene group and the alkenylene group are respectively and independently not replaced, or replaced with —O—, —NRB—(RB represents a hydrogen atom, a C1-6 alkyl group or a halo-C1-6 alkyl group), —S—, —S(═O)— or —S(═O)2—). Functional molecules include labels as well as purifying function. Cook et al. teaches their compound is used for labeling as well as purifying. The linker between the functional molecule and the nucleotide is an alkylene group with N and O substitutions which are linked to a nucleobase. This compound is taught by Cook et al. as being connected to oligonucleotides. Therefore, one skilled in the art would have been motivated to utilize this compound in order to provide functionality to the oligonucleotide as taught by Iriyama et al. with a reasonable expectation of success.
Regarding the instantly claimed structure in claim 8, 11, 17, 24, 50, 55, 81 and 84, An-Sp-D corresponds to:
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in the molecule of Cook et al.;
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when t is 1 and m is 3 and n is 1 in
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of Cook et al. The
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corresponds to L of
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when R10 is H, R13 is O-phosphate, B is 5-methylcytosine and R9 is oligonucleotide. Regarding E-X and F-Y, firstly, the two phosphate groups as shown above would serve as attachments in L of Iriyama et al. to X and Y which are taught as oligonucleotides which hybridize aka forms a duplex. It is taught that in the formula of
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X, Y, Xz and Yz are all oligonucleotides wherein Lx and Ly are linking groups which reads on selectively cleavable sites. Furthermore, Iriyama et al. teaches that the second nucleotide (Y) is a sequence that contains at least four contiguous nucleotides cleaved by RNase H which would read on a selectively cleavable site.
Regarding claim 9, An, Sp, D, L, LP, E and F are the same as set forth above. The tag recitation is indefinite for the reasons set forth above. However, claim 9 recites Bn represents the double-stranded oligonucleotide form by X and Y. Iriyama et al. teach and show hybridization of the oligonucleotide chains.
Regarding claim 10, 70,
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is a low molecular weight organic compound (as elected) and corresponds to at least α1 building blocks.
Regarding claim 36, E and F correspond to X and Y in Iriyama et al. X corresponds to a first oligonucleotide which is composed of 7 to 100 nucleotides. Y is a second oligonucleotide composed of 4 to 100 nucleotides (claim 1). Thus, Iriyama et al. teaches an overlapping range. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Note MPEP 2144.05.
Regarding claims 60-61, Iriyama et al. claim that Lx and Ly can be represented by P5-W5-P5 and P6-W6-P6 respectfully wherein W5 and W6 include deoxyribonucleotides (claim 1, see also paragraph 0169-0173). Examples of modifications of a base moiety in a deoxyribonucleotide include bromination, methylation, ethylation, etc. (paragraph 0184; 0191). It is taught that the four or more contiguous nucleotides recognized by RNase H are preferably deoxyribonucleotides (paragraph 0214; 0224). Therefore, Iriyama et al. clearly teaches the use of deoxyribonucleotides. This is further supported in the example (see table 7) which includes deoxythymidine, deoxyadenosine, deoxycytosine, deoxyguanosine. Since these bases can additionally be modified, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to one of ordinary skill in the art to combine the teachings of Iriyama et al. and Cook et al. and utilize any of the taught deoxyribonucleotides. One skilled in the art would manipulate the sequence depending on the sequence of the attached oligonucleotides. Since Iriyama et al. clearly teaches a preference for deoxyribonucleotides when forming regions which can be cleaved by RNase H, their use is obvious. While Applicants have preference for specific doexyribonucleotides, absent a demonstration of the criticality, it is the examiner positions that one skilled in the art would vary the nucleotide depending on the desired sequence.
Regarding claim 96, firstly, the scope of the claim is merely the compound of claim 8. Since this is rendered obvious above, the combination of Iriyama et al. and Cook et al. would suggest the library. The instant specification state that “a compound library” means a group of compound derivatives in which compounds having a specific activity are systemically collected (paragraph 0011 of the instant specification). Cook et al. teaches the luminescent metal ion complexes which are useful in detection and isolation of target analytes such as biomolecules. Suggesting a library as recited in the instant specification.
Double Patenting
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 8-11, 17, 24, 36, 50, 55, 60-61, 70, 81, 84 and 96 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 35-38, 43, 63, 77, 82, 97-88, 95, 109 and 121 of copending Application No. 18713086 (USPGPUB 20250215615). Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The instant application claims a compound represented by formula (II)
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wherein X and Y are oligonucleotide chains, E and F are each independently an oligomer constituted by nucleotides or nucleic acid analogues, provided that E and F contain base sequences, which are complementary to each other and form a duplex oligonucleotide, LP is a loop site, L is a linker and D is a divalent group derived from a reactive functional group, Sp is a bonding or a bifunctional spacer and An is a partial structure constituted by at least one building block, X and Y have a sequence capable of forming a duplex at least a part thereof, X binds to E at the 5' terminal end, Y binds to F at the 3' terminal end and has at least one selectively cleavable site at any of at least one site of E, F and LP.
As elected LP is
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and D is amino.
Copending ‘086 claims A method comprising a hairpin type DEL wherein the hairpin type DEL has a selectively cleavable site and is represented by formula I:
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Which is the same as instantly claimed (see claim 35). Claim 36 of copending ‘086 is the same as instantly claimed 9. Claim 37 of copending ‘086 is the same as instantly claimed 10 also reading on instant claim 70. Claim 38 of copending ‘086 is the same as instantly claimed 11. Claim 43 of copending ‘086 is the same as instant claim 17. Claim 63 of copending ‘086 is the same as instant claim 36. Claim 77 of copending ‘086 is the same as instant claim 50. Claim 82 of copending ‘086 is the same as instant claim 55. Claims 87-88 of copending ‘086 are the same as instant claim 60-61. Regarding instant claim 81, as set forth above, claim 35 of copending ‘086 claims Sp is a bond. Regarding claim 24, copending ‘086 claims the same LS and claims structures suggesting the claims in claim 38. Regarding claim 96, copending ‘086 claims a library in claim 1.
Conclusion
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.
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/ABIGAIL VANHORN/Primary Examiner, Art Unit 1636
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