Status of the Claims
Claims 1-24 are currently pending.
Claims 21-24 are withdrawn.
Claims 1-20 are examined herein.
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 Accordingly, Group II (claims 21-24) are withdrawn from consideration as directed to non-elected inventions.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.
Claim Interpretation
In several claims of the instant application, notably claims 1 and 17, the limitation of “operable for covalent cross-linking” is recited. The broadest reasonable interpretation of this limitation includes any functional group capable of covalent bonding and has been interpreted as such in the following office action. This includes functional groups that can directly crosslink with other molecules, as well as functional groups that can be chemically crosslinked via an intermediary crosslinking reagent.
Claim Rejections - 35 USC § 112
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.
Claims 7, 11, 19, and 20 are 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.
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Claim 7 depends on claim 6, which states “wherein L1 and L2 are independently an alkylene chain or poly(ethylene glycol) chain containing two functional groups… selected from the group consisting of a phosphate group, an amino group, a hydroxyl group, and a carboxyl group.” Claim 7 then states “L1 and L2 are independently ”. However, the second polyethylene glycol chain shown does not contain two functional groups selected from the list given in the preceding claim. Therefore, claim 7 does not include all limitations of claim 6. Accordingly, claim 19 does not include all limitations of claim 18, on which it is dependent.
Additionally, claim 11 is dependent on claim 10, which states that S1 and S3 carry “at least one functional group… selected from the group consisting of a phosphate group, an amino group, a hydroxyl group, a carboxyl group, an aldehyde group, an azido group, an alkynyl group, and a halogen”. Claim 11 then states that S1 and S3 are selected from a group of structures that contain an amino group, a carbonyl group, or none of the above. Of these, only the structures containing an amino group fall within the limitation put forth in claim 10. Therefore, the structures of claim 11 that do not contain an amino group do not include all limitations of claim 10.
Claim 20 is dependent on claims 19, 18, and 17. Claim 17 states that “R is a reactive group linked to a functional moiety”. In the instant specification, a “functional moiety” is defined as the small molecule part of the DNA-encoded compound library. However, the structures shown in claim 20, R is only a reactive group and is not linked to a functional moiety. Therefore, claim 20 does not include all limitations of claim 17.
Applicant may cancel the claims, amend the claims to place the claims in proper dependent form, rewrite the claims in independent form, or present a sufficient showing that the dependent claims comply with the statutory requirements.
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.
Claims 1-8 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) (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).
Regarding claim 6 and 7, Morgan discloses that L1 and L2 are independently a polyethylene glycol chain containing two phosphate groups, with a PEG unit repeat of 3 (p. 19, compound 2).
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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 1, wherein a total of at least 102 DNA-encoded compounds are contained in the DNA-encoded compound library (p. 2, ¶[0011-13]).
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 first and second linkers comprising a functional group capable of forming a covalent bond with the termini of Z1 and Z2 and are each independently a poly (ethylene glycol) chain containing two phosphate functional groups; 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
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, 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.
Claims 9-13 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 diphenyl ketone (benzophenone) group.
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Park Figure 4a(1), 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 use the photoaffinity linker of Park in the place of 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, above) has a structure of -S1-S2-S3-, wherein S1 and S3 are formed of a combination of carbon atoms and heteroatoms and each carry at least one functional group. Additionally, Park discloses that S2 is a linker that contains a group operable for covalent crosslinking. The at least one functional group carried in S1 and S3 are an amino and carbonyl, respectively. While a carbonyl is not listed in the Markush grouping of claim 10, it serves the same purpose of providing the linking chemistry between the modules. To one of ordinary skill in the art, it would be a trivial matter to exchange one method of chemical linkage for another, resulting in the
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inclusion of one of the listed functional groups, such as an amino group.
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Regarding claims 11-13, Park further discloses that S1 consists of and S3 consists of . Park also discloses that the group operable for covalent cross-linking is benzophenone, and is 6 atoms away from the functional moiety M (see Park Figure 4a(1) above).
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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 and L1 and L2 are polyethylene glycol chains containing two phosphate groups, with PEG unit repeats of 3. 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 claim 20, the combination of the Clark and Park elements as discussed above would produce a compound with high structural similarity to the compounds enumerated in claim 20. Here, the differences between the prior art and the instant claim lie in the directionality of the amide 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 directionality of the amide 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 claim 20 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.
Conclusion
No claims are allowed.
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/ALEXANDRA OLSON/Examiner, Art Unit 1684
/JEREMY C FLINDERS/Primary Examiner, Art Unit 1684