Status of the Claims
Claims 3-5, 8-10, and 12-25 are currently pending, with claims 21-24 withdrawn.
Claims 1-2, 6-7, and 11 were canceled.
Claims 3, 10, 15, and 17-19 were amended.
Claims 3-5, 8-10, 12-20, and 25 are examined herein.
The following Office Action is in response to Applicant's communication dated 4/27/2026. Rejection(s) and/or objection(s) not reiterated from previous office actions are hereby withdrawn. Specifically, the rejections of claims 7, 11, and 19-20 under 35 U.S.C. § 112(d) are withdrawn in light of Applicant’s amendments. The following rejections(s) and/or objection(s) are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-20) in the Response filed on 12/31/2025 is acknowledged. Accordingly, Group II (claims 21-24) are withdrawn from consideration as directed to non-elected inventions. Election was made without traverse in the reply filed on 12/31/2025.
Priority
The present application is a CON of PCT/CN2021/132846 (filed 11/24/2021) and further claims foreign priority to CN202011353377.7 (filed 11/27/2020). Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Modified Claim Rejections - 35 USC § 102
Necessitated by Amendments
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.
Morgan et al.
Claims 3-5, 8, and 14-16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Morgan et al. (PGPub No: US 2005/158765).
Regarding claim 1, Morgan discloses a DNA-encoded compound of formula (I) (p. 2, ¶[0009]; see annotated structure below) wherein X (S) is an atomic or molecular scaffold, A--1 (F-C-Y) is a first moiety comprising a first linker (F-C) and a first oligonucleotide (Y), A2 (E-B-Z) is a second moiety comprising a second linker (B-E) and a second oligonucleotide (Z), L (D-A) is a linker moiety comprising at least one group operable for covalent cross-linking, and M (X) is a functional moiety comprising at least one structural unit (p. 2, ¶ [0010]).
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Morgan p.2, annotated
Regarding claim 2, Morgan further discloses that X (S) is a carbon atom, a nitrogen atom, or a molecular scaffold (p. 13, ¶[0111]).
Regarding claim 3, Morgan discloses a DNA-encoded compound of formula (II), wherein X (S) is a carbon atom, a nitrogen atom, or a molecular scaffold (p. 13, ¶[0111]); M (X) is a functional moiety comprising at least one structural unit (p. 2, ¶ [0010]); L (D-A) is a linker moiety comprising at least one group operable for covalent cross-linking; Z1 (Y) is a first oligonucleotide with its 5’ terminus attached to L1 (C-F) and Z2 (Z) is a second oligonucleotide with its 3’ terminus attached to L2 (E-B) (p. 2, ¶[0010]); and L1 and L2 are polyethylene glycol chains of 2 repeats linked to the scaffold with a phosphate group and are linked to the oligonucleotides with, independently, either a phosphate or ether group (p. 15, Compound 1 – annotated below).
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Morgan – Compound 1, annotated
Regarding claim 3, Morgan discloses a DNA-encoded compound of formula (II) (see annotated structure above), wherein Z1 (Y) is the first oligonucleotide with its 5’ terminus attached to L1 (C-F) and Z2 (Z) is the second oligonucleotide with its 3’ terminus attached to L2 (E-B), L1 is the first linker comprising a first functional group (C) capable of forming a covalent bond with the 5’ terminus of Z1, and L2 is the second linker comprising a second functional group (B) capable of forming a covalent bond with the 3’ terminus of Z2 (p. 2, ¶[0010]).
Regarding claim 4, Morgan discloses that Z1 and Z2 are at least partially complementary to each other to form a double-stranded structure (p. 2, ¶[0008], lines 13-15), Z1 and Z2 each independently have a length of at least 10 bases, and a complementary region of Z1 and Z2 has a length of at least 10 bases (p.12-13, ¶[0110]).
Regarding claim 5, Morgan further discloses that Z1 and Z2 each independently has a polymerase chain reaction (PCR) primer sequence (p. 11, ¶[0092], lines 2-4).
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Regarding claim 8, Morgan discloses that at least one group contained in L is a group capable of forming covalent cross-linking with a protein (p. 8, ¶[0073], lines 6-9).
Regarding claim 14, Morgan discloses that X (S) is (p. 15, compound 1).
Regarding claims 15 and 16, Morgan discloses a DNA-encoded compound library that consists of the DNA-encoded compound of claim 3, wherein a total of at least 102 DNA-encoded compounds are contained in the DNA-encoded compound library (p. 2, ¶[0011-13]).
Clark et al.
Claims 17 and 18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Clark et al. (Nature Chem. Biol., 2009, 5(9): 647-654, cited in IDS of 5/26/23).
Regarding claims 17 and 18, Clark teaches a starting fragment compound of formula (III) (Sup. Figure 2 (p.18), annotated below) wherein X is a molecular scaffold; Z1 is a first oligonucleotide of consisting of 8 nucleotides with its 5’ terminus attached to L1 and is complementary to Z2 is a second oligonucleotide consisting of 6 nucleotides with its 3’ terminus attached to L2; L1 and L2 are polyethylene glycol chains of 2 repeats linked to the scaffold with a phosphate group and are linked to the oligonucleotides with, independently, either a phosphate or ether group; L is a linker moiety comprising at least one group operable for covalent cross-linking with a protein; and R is an amino group linked to a functional moiety (p. 648, Figure 1; col. 2, lines 12-13).
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Clark Sup. Figure 2, annotated
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Response to arguments
In the Remarks dated 4/27/2026 Applicant argues that Morgan and Clark do not teach the amended limitation of claims 3 and 17 regarding L1 and L2, specifically the newly added limitation that “one of L1 and L2 is
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, and the other of L1 and L2 is
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”.
Applicant’s arguments have been fully considered but they are not persuasive for the following reasons.
Applicant contends that compounds of Morgan and Clark comprise linkers with phosphates on both ends of each linker. However, claims 3 and 17 also state “Z1 is a first oligonucleotide with its 5' terminus attached to L-1, and Z2 is a second oligonucleotide with its 3' terminus attached to L2”, or with the 3’/5’ termini switched. Additionally, the 5’ terminus of an oligonucleotide is frequently phosphorylated. Therefore, under the interpretation of the claim that the 5’ terminus connected to L1 is phosphorylated, L1 is
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, as indicated on the annotated structures of Morgan and Clark, above. Therefore, the rejections of claims 3 and 17 as being anticipated by Morgan and Clark, respectively, are proper.
Modified Claim Rejections - 35 USC § 103
Necessitated by Amendments
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.
Morgan et al., Park et al., and Denton et al.
Claims 9-10 and 12-13 are rejected under 35 U.S.C. 103 as being unpatentable over Morgan et al. in view of Park et al. (ACS Chem. Biol. 2016, 11(1): 44–52) and Denton et al. (Med. Chem. Commun., 2016, 7: 2020-2027).
Regarding claim 9, Morgan teaches all limitations of claim 8 as discussed above. Morgan does not teach that at least one group contained in L is selected from the group listed in claim 9.
Park discloses a photoaffinity linker (Park Figure 4a(1), annotated below) connected to a functional moiety (M). The linker includes a tag/handle region with an alkyne functional group, allowing for labeling via click chemistry instead of a DNA tag. Additionally, Park discloses that the linker contains a diazirine group.
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Park Figure 4a(2), annotated
Additionally, Park discloses that use of the photoaffinity linker allows for capture of low affinity interactions because of the ability of the photoactivatable moiety to covalently bond with adjacent molecules, thereby maintaining the interaction throughout unfavorable experimental conditions or washing steps (Park, p. 44). The loss of low affinity ligands is also widely known to be a common issue when screening DNA-encoded chemical libraries (Denton, abstract). Therefore, the motivation for applying the linker of Park to the DNA-encoded compound of Morgan would have been known to one of ordinary skill in the art at the time of the effective filing date of the instant application.
Furthermore, one would have a reasonable expectation of success of combining these compounds because photoaffinity linkers have previously been incorporated into DNA-encoded compounds. Among others (including WO 2019/149198 A1), Denton discloses a DNA-encoded compound with a photoaffinity crosslinking group, showing that their use allows the capture of low affinity ligand interactions.
Therefore, it would have been obvious to one of ordinary skill in the art at the effective filing date of the present application to incorporate the photoaffinity linker of Park into the linker (L) of the DNA-encoded compound of Morgan, with a reasonable expectation of success.
Regarding claim 10, Park discloses that the photoaffinity linker (see Park Figure 4a(2), above) has a structure of -S1-S2-S3-, wherein S1 consists of
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and S3 consists of
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. Additionally, Park discloses that S2 is a linker that contains a group operable for covalent crosslinking.
Regarding claims 12-13, Park further discloses that the group operable for covalent cross-linking is diazirine, and is 9 atoms away from the functional moiety M (see Park Figure 4a(2) above).
Clark et al., Park et al., and Denton et al.
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Claims 19 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Clark et al. in view of Park et al. and Denton et al.
Regarding claim 19, Clark discloses that X is where q is 4. Park discloses the limitations of L and S2 as discussed in regards to claim 10. It would have been obvious to combine the linker of Park with the starting fragment of Clark as per the reasoning set forth in the discussion of claim 9.
Regarding claims 20 and 25, the combination of the Clark and Park elements as discussed above would produce a compound with high structural similarity to the compounds enumerated in claims 20 and that shown in claim 25. Here, the differences between the prior art and the instant claim lie in the chemical identity of the linkages and the number of repeating (CH2) groups contained within each linker. These differences are trivial in that they are not likely to affect the properties and function of the compound and one of ordinary skill in the art would be able to construct such variations using commercially available building blocks. As an illustration of this concept, Park further reports additional photoaffinity linkers (Park Figure 4a, below) that vary in terms of the chemical identity of the linkages, as well as in the number of (CH2-) groups.
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Park Figure 4a
Additionally, MPEP § 2144.09 states,
Compounds which are position isomers (compounds having the same radicals in physically different positions on the same nucleus) or homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties.
As the compounds listed in claims 20 and 25 would be easily synthesized by one of ordinary skill in the art based on the teachings in Clark and Park, while maintaining similar structure, properties, and function, the compounds would have been obvious by the effective filing date of the application.
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Response to arguments
Applicant does not offer further arguments regarding these obviousness rejections beyond what was set forth above. To that extent, the Examiner contends that those issues were adequately addressed in the above sections, which are incorporated in their entireties herein by reference.
Conclusion
No claims are allowed.
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.
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/ALEXANDRA OLSON/Examiner, Art Unit 1684
/JEREMY C FLINDERS/Primary Examiner, Art Unit 1684
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