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 .
Application Status
The action is written in response to the applicant’s correspondence received on 4/26/2024. Claims 1, 3-9, 11, 13-21, 25, and 37 are currently pending.
Priority
The instant application claims priority to US Provisional application 63/273,666, with an effective filing date of 10/29/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 4/26/2024. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claims 1, 3-9, 11, 13-21, 25, and 37 are under examination of the merits.
Claim Interpretation
Regarding claim 6, 15, and 18, applicant recites where the antigen is “(i) a length and width in angstroms or nanometers from other antigens on the target analyte”. It is known to a skilled artisan that both are units of length, which can be represented in different units, such as angstrom or nanometers. In the instant case, 1 angstrom is simply 0.1 nanometers, therefore examiner will interpret these claims as wherein the antigen is “a length and width from other antigens on the target analyte”.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1 and 3-9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kwon et al. (Designer DNA architecture offers precise and multivalent spatial pattern-recognition for viral sensing and inhibition, Nature Chemistry, Volume 12, pgs. 26-35, published 11/25/2019).
Regarding claim 1, Kwon discloses an artificial biopolymer complex, evidenced by a customized DNA architecture nanostructure, wherein the disclosure is related to artificial biopolymer complex (see abstract) comprising a network of polynucleotides (DNA star structure, see Fig. 1C), comprising structural units (triangle-shaped DNA unit of star-shaped DNA structure, see Fig. 1C) connected to one another via a series of arms and junctions (See Fig. 1C).
Kwon discloses the artificial biopolymer complex has each of the structural units with a predetermined shape defined by one or more strands of polynucleotide (structural unit with triangle base shape (predetermined) defined by one or more strands of polynucleotides, see Fig. 1C), where at least a portion of one or more strands of polynucleotides of each structural unit is complementary to at least a portion of the one or more strands of polynucleotides of another structural unit (portion of the structural unit comprised of Edge-2 is complementary to a portion of the structural unit comprised of Fix-1, see Fig. 1D), and the complementary portions of the strands of the polynucleotides of adjacent structural units are hybridized to connect the adjacent structural units (complementary portions of the strands of the polynucleotides of adjacent triangle-shaped structural unit polynucleotides of adjacent triangle-shaped structural unit comprised of Edge-2 is hybridized to connect the adjacent structural unit comprising Fix-1, indicated by red arrows, see Fig. 1D), the complementary portions of the strands of the polynucleotides of adjacent structural units form the arms (See Fig. 1B) with a predetermined length (DNA star scaffold is designed to match spacing of ED3 clusters, wherein the arms comprising trivalent-pentavalent clusters are 14.3 nm long center to center, see Figs. 1A and 1B) and the intersections of the two or more arms form the junctions at a predetermine distance from one another (intersection of two or more arms form junctions 15.3 nm from one another, see Fig. 1A and 1B) based on the predetermined length of the arms. The predetermined distance is in the range of 5 nm to 999 nm (distance between the intersection of two or more arms forming the junctions is 15.3 nm center to center, see Fig. 1A).
Kwon further teaches where antigen binders attach to the surface of the network of polynucleotides, wherein the antigen binders bind to antigens of a target analyte (aptamers, or antigen binders, Fig. 4D, are incorporated at the junctions of the DNA nanostructure, Fig. 6D, where ED3 targeting aptamers provide virus-binding (target analyte binding) avidity, where the disclosure of Kwon is related to antigen binders binding to antigens of a target analyte (see abstract). Kwon discloses where at least some of the antigen binders are attached at uniquely addressable loci on the arms forming the junctions (heptagon-shaped DNA structure contain a seven-arm junction, with heptavalent binding sites on anthrax (uniquely addressable loci on the arms forming junctions), Fig. 6D), wherein the uniquely addressable loci are separated by predetermined inter-binder distance (Fig. 6 depicts principles of design for DNA nanostructures, where binding sites of spatial patterns are analyzed, a nanostructure was designed based on the analysis that incorporates binding at appropriate locations, wherein these locations are at predetermined distances in the nanostructure based on the binding site patterns, See Fig. 6) such that the antigen binders are positioned on the network of polynucleotide in a predetermined two-dimensional or three-dimensional spatial pattern that matches a two-dimensional or three-dimensional spatial pattern of the antigens on the target analyte (two-dimensional spatial pattern of binding sites on DNA nanostructure matches the two-dimensional spatial pattern of binders of the target analyte, see Figs. 6A-6E).
Regarding claim 3, Kwon discloses where each structural unit of the artificial biopolymer of claim 1 is defined by six or more polynucleotides (each structural unit is composed of 10 external edges that are 42 bp long, see pg. 27, first column, third paragraph).
Regarding claim 4, Kwon discloses the artificial biopolymer of claim 1 wherein the two-dimensional or three-dimensional spatial pattern of the binders is defined by intermolecular spacing of the antigens on the surface of the target analyte (two-dimensional spatial pattern of the binders is defined by precisely matching the spatial surface pattern (intermolecular spacing) of the binders (antigens) on the viral surface (target analyte), see abstract and Figs. 1A and 6) and wherein the predetermined inter-binder distances of the uniquely addressable loci of the antigen binders match the intermolecular spacing of the antigens such that the antigen binders on the network of polynucleotides align spatially with the antigens on the surface of the target analyte (aptamers bind onto DNA architecture in a 2D pattern precisely matching the spatial arrangement of clusters on viral surface with predetermined inter-binder distances, see abstract and Figs. 1A and 4D).
Regarding claim 5, Kwon discloses the artificial biopolymer complex of claim 4, where the predetermined inter-binder distances of the uniquely addressable loci of the antigen binders match the intermolecular spacing of the antigens such that the antigen binders match the intermolecular spacing of the antigens such that the antigen binders on the surface of the network polynucleotides spatially align with the antigens on the surface of the target analyte (aptamers bind onto DNA architecture in a 2D pattern precisely matching the spatial arrangement of clusters on viral surface with predetermined inter-binder distances, see abstract, Figs. 1A and 4D).
Regarding claim 6, Kwon discloses the artificial biopolymer complex of claim 1 and where each of the antigens is (i) a length and width in angstroms or nanometers from other antigens on the target analyte (length between target analyte binding sites is an even distance of 36.3, Fig. 6B) and each antigen binder is a length and width in angstroms or nanometers from other antigen binders on the network of polynucleotides (length between antigen binders is 36, Fig. 6C), and the predetermined inter-binder distances of the uniquely addressable loci of the antigen binders match the intermolecular spacing of the antigens such that the antigen binders on the first surface of the network of polynucleotides align spatially with the antigens on the surface of the target analyte (aptamers bind onto DNA architecture in a 2D pattern precisely matching the spatial arrangement of clusters on viral surface with predetermined inter-binder distances, abstract, Fig. 1A and 4D).
Regarding claim 7, Kwon discloses the artificial biopolymer complex of claim 1 and where the antigens form antigen clusters on the target analyte (Fig. 1A) and wherein at least some of the antigen binders are arranged in antigen binding clusters (antigen binding aptamers in a 2D pattern precisely matching the spatial arrangement of clusters on the viral surface, abstract, Figs. 1A and 4D), each antigen binder is attached to one of the two or more arms that form a junction (Fig. 6D), the binders of each antigen binder cluster are attached to the arms at uniquely addressable loci that are a predetermined distance from the junction, wherein the unique addressable loci are separated by predetermined intra-cluster binder distances such that the binders of each antigen binder cluster are positioned on the network of polynucleotides in a predetermined two-dimensional or three-dimensional spatial pattern that matches a two-dimensional or three-dimensional spatial pattern of the antigens in an antigen cluster (clusters of binders with predetermined spacing between the binders, and junctions matching the spatial pattern of the two different target antigen clusters, Figs. 1A and 4D).
Regarding claim 8, Kwon discloses the artificial biopolymer complex of claim 1 and wherein the binders from different clusters of antigen binders are separated by intercluster binder distance such that different antigen binder clusters are positioned on the network of polynucleotides in a predetermined two-dimensional or three-dimensional spatial pattern that matches a two-dimensional or three-dimensional spatial pattern of the antigen clusters (clusters of binders with predetermined spacing distance between the binders and junctions matching the spatial pattern of the trivalent and pentavalent target antigen clusters target antigen clusters, Figs. 1A and 4D).
Regarding claim 9, Kwon teaches the artificial biopolymer complex of claim 7 and wherein the predetermined intra-cluster binder distances of the uniquely addressable loci of the binders of each antigen binder cluster is between 1 nm and 15nm (distance between adjacent loci of antigen binders is 10.5 nm, Fig. 2A).
In view of the foregoing, claims 1 and 3-9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kwon.
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.
Claims 11, 13-19, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Kwon et al. (Designer DNA architecture offers precise and multivalent spatial pattern-recognition for viral sensing and inhibition, Nature Chemistry, Volume 12, pgs. 26-35, published 11/25/2019) in view of Chen et al. (Fusion protein linkers: Property, design, and functionality, Advanced Drug Delivery Reviews, Volume 65, Issue 10, pgs. 1357-1369, published 10/15/2013).
Regarding claim 11, Kwon teaches an artificial biopolymer complex (star-shaped DNA architecture nanostructure, abstract) comprising a chain of polynucleotide hybridized to a structural chain of polynucleotides (aptamers hybridized to each of the vertices of 42 bp long external chains, pg. 28, first column, second paragraph, Fig. 2A), wherein at least a portion of each chain of the connector chains is complementary to at least a portion of the structural chain (star showing portion of aptamer connecting chain is hybridized to, therefore complementary to, structural chains, Fig. 2A), and the complementary portions of the connector chains and structural chain are hybridized to connect the connector chains to the structural chain (star showing portion of aptamer connecting chain is hybridized to, therefor complementary to, structural chains, Fig. 2A).
Furthermore, Kwon discloses antigen binders attached to a first surface of the network of polynucleotide (aptamers attached onto DNA scaffold, Fig. 4D), wherein the antigen binders bind to antigens of a target analyte (aptamers with high virus-binding avidity, abstract) and the antigen binders are attached at uniquely addressable loci on the structural chain via the connector chains, wherein the uniquely addressable loci are separated by predetermined inter-binder distances such that the antigen binders are positioned on the network of polynucleotides in a predetermined two-dimensional or three-dimensional spatial pattern that matches a two-dimensional or three-dimensional spatial pattern of the antigens on the target analyte (aptamers constructed on unique loci at junctions of DNA structural architecture in a 2D pattern precisely matching the spatial arrangement of clusters on viral surface with predetermined inter-binder distances, abstract, Figs. 1A and 4D).
Regarding claim 13, Kwon teaches where a network of polynucleotides forms a tile, a tube, or a tetrahedron (DNA was constructed using the tile-based self-assembly of 21 DNA oligonucleotides, pg. 27, first column, third paragraph).
Regarding claim 14, Kwon teaches the two-dimensional or three-dimensional spatial pattern of the antigens is defined by intermolecular spacing of the antigens on the surface of the target analyte (aptamers constructed on the DNA architecture is a 2D pattern precisely matching the spatial arrangement of clusters on viral surface, abstract, Figs. 1A and 4D), and wherein the predetermined inter-binder distances of the uniquely addressable loci of the antigen binders match the intermolecular spacing of the antigens such that the antigen binders on the first surface of the network of polynucleotides align spatially with the antigens on the surface of the target analyte (aptamers constructed on DNA architecture in a 2D pattern precisely matching the spatial arrangement of clusters on viral surface, abstract, Figs. 1A and 4D).
Regarding claim 15, Kwon further teaches where each of the antigens is (i) a length and width in angstroms or nanometers from other antigens on the target analyte (length between target binding sites is an even distance of 36.3, Fig. 1B), and each antigen binder is (i) a length and width in angstroms or nanometers from other antigen binders on the network of polynucleotides (length between aptamers is 36, Fig. 1C), and the predetermined inter-binder distances of the uniquely addressable loci of the antigen binders match the intermolecular spacing of the antigens such that the antigen binders on the network of polynucleotides align spatially with the antigens on the surface of the target analyte (aptamers constructed on DNA architecture in a 2D pattern precisely matching the spatial arrangement of clusters on viral surface with predetermined inter-binder, abstract, Figs. 1A and 4D).
Regarding claim 16, Kwon further discloses wherein the antigens form clusters on the target analyte (antigen clusters on target analyte, Fig. 1A), wherein at least some of the antigen binders are arranged in antigen binder clusters (antigen binding aptamers in a 2D pattern precisely matching the spatial arrangement of clusters on the viral surface, abstract, Figs. 1A and 4D), each binder of the antigen binder cluster is hybridized to uniquely addressable loci on the structural chain (antigen binders each hybridized to unique loci on structural chains, Fig. 4D), wherein the uniquely addressable loci are separated by predetermined intra-cluster binder distances such that each antigen binder cluster are positioned on the network of polynucleotides in a predetermined two-dimensional or three-dimensional spatial pattern that matches a two-dimensional or three-dimensional spatial pattern of the antigens in an antigen cluster on the target analyte (binder clusters constructed on unique loci at regularly spaced junctions of DNA structural architecture in at predetermined distances in a predetermined 2D pattern precisely matching the spatial arrangement of clusters on viral surface, abstract, Figs. 1A and 4D).
Regarding claim 17, Kwon teaches wherein the binders of different clusters of antigen binders are separated by a predetermined inter-cluster distance such that antigen binder clusters are positioned on the network of polynucleotide in a predetermined two-dimensional or three-dimensional spatial pattern that matches a two-dimensional or three-dimensional spatial pattern of the antigen clusters (binders constructed on unique loci at regularly spaced junctions of DNA structural architecture in a predetermined 2D pattern precisely matching the spatial arrangement of separate clusters on the viral surface, abstract, Figs. 1A and 4D).
Regarding claim 18, Kwon teaches where each antigen binder in an antigen binder cluster is (i) a length and width in angstroms or nanometers from other binders of the antigen binder cluster on the network of polynucleotides (clusters of binders with predetermined, regular spacing distance 36 between the binders within a cluster matching the spatial pattern of trivalent and pentavalent target antigen clusters, Fig. 6C), and the predetermined intra-binder distances of the uniquely addressable loci of the binders of each antigen binder cluster match intermolecular spacing of the antigens in each cluster such that the binders in the antigen binder cluster on the network of polynucleotides align spatially within the antigens in an antigen cluster (intra-binder distances precisely match intermolecular spacing of viral surface antigens in each cluster at unique loci at regular spaced junctions of DNA structural architecture in a predetermined 2D pattern, abstract, Figs. 1A and 4D).
Regarding claim 19, Kwon teaches wherein the predetermined intra-cluster binder distances of the uniquely addressable loci of each antigen binder cluster is between 1 nm and 15 nm (distance between adjacent trivalent-trivalent antigen binders is 10.5 nm, Fig. 2A).
Regarding claim 21, Kwon teaches wherein each of the antigens comprise one or more epitopes or domains (Kwon targets envelope protein domain III (ED3) as the antigen on the DENV surface, which means ED3 has other domains, see results section), wherein the first set of binders are arranged in sets of clustered antigen binders, Fig. 1B), each binder of a set of clustered antigen binders is attached to one of the two or more arms that form a junction (Fig. 1A and 1B), and where the binders of each of the sets of clustered antigen binders are attached to the arms at uniquely addressable loci that are a predetermined distance from the junction, wherein the uniquely addressable loci are separated by predetermined intra-binder distances such that each set of clustered antigen binders are positioned on the network of polynucleotides in a predetermined two-dimensional or three-dimensional spatial pattern that matches a two-dimensional or three-dimensional spatial pattern of the one or more epitopes on an antigen (intra-binder distances precisely match intermolecular spacing of viral surface antigens in each cluster at unique loci at regular spaced junctions of DNA structural architecture in a predetermined 2D pattern, abstract, Figs. 1A and 4D).
Regarding claim 11, Kwon does not teach a network of polynucleotides comprising connector chains of polynucleotides attached to a structural chain of polynucleotides, wherein the connector chains are shorter than the structural chain.
Regarding claim 11, Chen teaches a network of polynucleotides comprising connector chains of polynucleotides attached to a structural chain of polynucleotides, wherein the connector chains are shorter than the structural chain (widely used flexible linker (Gly-Gly-Gly-Gly-Ser)n of 5 amino acids which is shorter than the 42 bp external edge structural chains of Kwon, is used to join domains that require a certain degree of movement or interaction, pg. 4, fourth paragraph).
It would have been obvious to one with ordinary skill in the art, before the effective filing date, to combine the teachings of Kwon and Chen, to arrive at an artificial biopolymer complex comprising a network of polynucleotides comprising connector chains of polynucleotides attached to a structural chain of polynucleotides, wherein the connect chains are shorter than the structural chain.
One would expect a reasonable chance of success as Chen teaches connector chains of polynucleotides attached to a structural chain of polynucleotides wherein the connector chains are shorter than the structural chain of polynucleotides. Chen further discloses the use of flexible linkers, and linkers in general, in a polynucleotide or polypeptide construct for the purpose of improving biological activities, increasing production, achieving a controlled or targeted drug delivery, as well as achieving desirable PK profiles of the fusion proteins (see Chen, Section 5).
One would be motivated to combine the arts of Kwon and Chen at the time the invention was made in order to modify the artificial biopolymer complex of Kwon with the flexible linker connector of Chen for the benefit of attaching an aptamer in a way that allows movement and interaction of the aptamer with the virus (see Chen, pg. 4, fourth paragraph). The increase in binding of aptamers with antigens of the virus would allow for better detection and inhibition of a target analyte (DNA star was functionalized for DENV detection and inhibition by hybridizing a well characterized, ED3-binding aptamer at each of the 10 vertices of the DNA star matched and targeted to ED3 clusters (Fig. 2A).
In view of the foregoing, claims 11, 13-19, and 21 are rejected under 35 U.S.C. 103 as being prima facie obvious, before the effective filing date.
Claims 20, 25, and 37 are rejected under 35 U.S.C. 103 as being unpatentable over Kwon et al. (Designer DNA architecture offers precise and multivalent spatial pattern-recognition for viral sensing and inhibition, Nature Chemistry, Volume 12, pgs. 26-35, published 11/25/2019) in view of Chen et al. (Fusion protein linkers: Property, design, and functionality, Advanced Drug Delivery Reviews, Volume 65, Issue 10, pgs. 1357-1369, published 10/15/2013) in further view of Sigl et al. (Programmable icosahedral shell system for virus trapping, Nature Materials, Volume 20, pgs. 1281-1289, published 6/14/2021) and Chang et al. (US 8440811 B2, published 5/14/2013).
Regarding the artificial biopolymer of claim 11, the combined teachings of Kwon and Chen would allow a skilled artisan to arrive at an artificial biopolymer complex comprising connector chains wherein the connector chains are shorter than the structural chain.
Regarding claim 20, Kwon teaches where ED3-binding aptamers are attached to each of the 10 vertices of the DNA star to form a star-aptamer complex that geometrically matched and target ED3 clusters (Fig. 2A). A skilled artisan could envision that as aptamers are placed on the inner vertices of the star (see Fig. 2A), the aptamers would be at least partially enveloped as the DNA star curves around the target virus. The claim limitations broadly recite “at least partially enveloped” which could include a single nucleotide and Kwon does teach where the DNA star scaffold has a curvature in response to binding an antigen or virus (Two more simple examples, where curvature is not account for, are used for illustrations, Fig. 6D and 6E). However, to strengthen this argument, further prior art is brought in.
Regarding claim 20, Sigl teaches DNA assembled into shells to envelope viruses with an internal cavity diameter of up to 280 nm, wherein the shell interior can be functionalized with virus-specific moieties (such as aptamers) in a modular fashion (see abstract of Sigl). This is further evidenced where Sigl teaches where multivalency can support tight binding of a target virus even for individually weakly virus-binding molecules, as exemplified in previous experiments with star-shaped DNA aptamer clusters that simultaneously target multiple dengue virus envelop proteins and where candidate virus binders could be, for example, antibodies, designed proteins, nucleic acid aptamers, or other polymers (see section titled “main”, paragraph 2).
Regarding claim 37, Kwon teaches a method for treating a subject, the method comprising obtaining the artificial biopolymer complex of claim 1 and administering the artificial biopolymer complex to the subject in an amount sufficient to provide a treatment effect (viral inhibition over time during DNA star treatment, Fig. 5A).
Regarding claim 25, Kwon does not teach where the network of polynucleotides has a second surface, and the second surface is attached with biomarker binders.
Regarding claim 25, Chang teaches a DNA scaffold comprising a first ligand capable of binding to one cell type and a second ligand that is capable of binding to another cell type, wherein it is preferred the first and/or second ligands are aptamers (see column 2, line 28 and 36). Chang teaches where a first surface of is attached with antigen binders (first ligand is an aptamer where the first aptamer comprises a dimer, trimer, tetramer, or pentamer of an aptamer that is capable of binding to a receptor of the first cell type, see column 2, line 28) and a second ligand that is attached with biomarker binders (second ligand is an aptamer and where the second aptamer comprises a dimer, trimer, tetramer, or pentamer of an aptamer that is capable of binding to a receptor of the second cell type, see column 2, line 28). Chang also teaches where the first aptamer is capable of binding to a T cell receptor or a natural killer (NK) cell receptor (see column 3, line 3). Looking to the instant specification for guidance, the instant applicant defines “biomarker” as “each target a biomarker on an immune cell, such as CD3, which is a T-cell receptor (see paragraph 00115 of the instant specification). The first and/or second aptamers of Chang are merely for identifying two aptamers, one of which that binds to a T cell and another that binds to a tumor antigen, therefore the first aptamer of Chang can correspond with the second aptamer of the instant invention. As Chang teaches the first aptamer can bind to T cell receptors, Chang therefore teaches wherein the second aptamer can bind to biomarkers on immune cells. Fig. 13A-D of Chang displays the different configuration of aptamers binding on two surfaces, whether it’s on the same side orientation, or opposite.
Regarding claim 37, Chang teaches where the present invention provides methods for treating a tumor in a mammal comprising administering to a mammal in need thereof an amount effective of the composition to treat the tumor (see column 3 of Chang).
It would have been obvious to one with ordinary skill in the art, before the effective filing date of the claimed invention, to combine the teachings of Kwon, Chen, Sigl, and Chang, to arrive at the instantly claimed invention, which is a network of polynucleotides comprising shorter or more flexible connector chains, wherein the surface has a curvature such that the antigen binders are at least partially enveloped by a surface of the network polynucleotides, and where there are two surfaces on the polynucleotide network, wherein the first surface comprises antigen binders and second surface is attached with biomarker binders.
One would expect a reasonable chance of success as Chen teaches flexible linkers or chain connecters that are shorter than the structural polynucleotide and modifying Kwon with shorter connectors would increase flexibility of aptamer binding. Furthermore, Sigl recites the art of Kwon and modifies it further by using DNA nanostructures with interior aptamers to envelope a virus and Chang teaches where DNA nanostructures can comprise two aptamers capable of binding two different cell types, one of which is immune cells.
One would be motivated to combine these arts to improve the DNA scaffold of Kwon to create a DNA nanostructure that allows for aptamer flexibility (evidenced by Chen) with stronger binding affinity due to interior aptamers that are enveloped by the surface of the network of polynucleotides (with shells that fully cover viruses, an even larger degree of multivalency, and thus stronger binding, can be envisioned, section “main”, paragraph 2 of Sigl), and where the DNA nanostructure has a second surface that targets receptors of an immune cell. Chang solidifies the motivation by disclosing CD8 T cells and natural killer cells are major players in tumor immunity, however, tumor cells often contain genetic alterations that result in reduced levels of MHC I expression to evade immune surveillance. Chang’s teachings allow for a DNA nanostructure to bind onto an immune cell through a “biomarker binder” and then bind onto a tumor cell with an aptamer “or antigen binder”, for the treatment of a tumor in a mammal (see column 3 of Chang).
In view of the foregoing, claims 20, 25, and 37 are rejected under 35 U.S.C. 103 as being prima facie obvious, before the effective filing date.
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 1, 3-9, 11, 13-21, 25, and 37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 and 40 of copending Application No. 18/037, 433 in view of Kwon et al. (Designer DNA architecture offers precise and multivalent spatial pattern-recognition for viral sensing and inhibition, Nature Chemistry, Volume 12, pgs. 26-35, published 11/25/2019), Chen et al. (Fusion protein linkers: Property, design, and functionality, Advanced Drug Delivery Reviews, Volume 65, Issue 10, pgs. 1357-1369, published 10/15/2013), Sigl et al. (Programmable icosahedral shell system for virus trapping, Nature Materials, Volume 20, pgs. 1281-1289, published 6/14/2021), Chang et al. (US 8440811 B2, published 5/14/2013), and Georges et al. (US 20210260181 A1, published 8/26/2021).
Regarding claims 1, 3-9, 11, 13-21, 25, and 37 of the instant application recites an artificial biopolymer complex connected to one another via a series of arms and junctions, wherein each of the structural units has a predetermined shaped defined by one or more strands of polynucleotides, where at least a portion of the one or more strands of polynucleotides of each structural unit is complementary to at least a portion of the one or more strands of polynucleotides of another structural unit, and the complementary portions of the strands of the polynucleotides of adjacent structural units are hybridized to connect the adjacent structural units, the complementary portions of the strands of the polynucleotides of adjacent structural units form the arms with a predetermined length, and the intersections oft het wo or more arms form the junction at a predetermined distance from one another based on the predetermined length of the arms, wherein the predetermined distance is in a range of 5 nm to 999 nm, and where antigen binders are attached to a surface of the network of polynucleotides, wherein the antigen binders bind to antigens of a target analyte. Both applications further recite a method for treating a subject, comprising obtaining and administering the artificial biopolymer complex to the subject in an amount sufficient to provide a treatment effect.
Claims 1-26 of the of the co-pending application recite nearly identical subject matter with regards to the structure of the artificial biopolymer complex, except for the arm lengths being in the range of 5 nm to 999 nm (see claim 1 of the instant application) and shorter connector chains (see claim 11 of the instant application), locking molecules and fluorophores attached to the binders (see claims 22-26 of the copending application), and target analyte. This discrepancy is alleviated by Kwon, which anticipates the structure of claim 1 of the instant application (see rejection above) and further modified by Chen, which includes flexible linkers or shorter connecter arms (claim 11) (see rejection above).
Regarding claims 22-26 of the copending application, Kwon teaches where the DNA star forms a star-aptamer complex that geometrically matches and targets ED3 clusters, FAM-BHQ (fluorophore-quencher) pairs on all inner edges, arranged in a quenching FRET by DNA base pairing in the hairpins (see Fig. 2).
While the copending application recites where the target analyte is SARS-CoV-2, and the antigens comprise trimeric spike glycoproteins (see claim 18 of the copending application), the instant application does not specify a target analyte, until claim 25, where it discloses where an aptamer can recognize a biomarker on an immune cell.
Regarding claim 18 of the copending application, Kwon does not teach where the target analyte is a SARS-CoV2- spike protein, instead teaching ED3 viral protein. Georges teaches a spike protein is a major antigen of coronavirus (see paragraph 0005, 0172, and 0173 of Georges.
It would have been obvious to modify the copending application with the prior art above to arrive at the invention of the instant application. Regarding the composition of the instant application and copending application, the modification of the copending composition would be identical to that of the instant application. Furthermore, while the copending application recites targeting SARS-CoV2, a skilled artisan would realize that if the structure of the composition is taught, then the function of targeting a specific analyte is deemed an inherent function of the structure, see MPEP § 2112.03. Therefore, the composition of the instant application could target any analyte known in the art.
A skilled artisan would have had a reasonable expectionat of success for targeting either the analyte of the instant application or copending application as evidenced by Kwon and Georges where Kwon already teaches a DNA nanostructure used to target viral proteins and where Georges specifically teaches the Spike protein is an antigen of SARS-CoV2. Vice versa, a skilled artisan would modify the copending application with the teachings of Chang (described above) to target an immune cell, as recited in the instant application.
Therefore, the invention as a whole would have been prima facie obvious before the effective filing date of the claimed invention.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3-9, 11, 13-21, and 25 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7-12, 21, 22 of copending Application No. 17/612,000 in view of Kwon et al. (Designer DNA architecture offers precise and multivalent spatial pattern-recognition for viral sensing and inhibition, Nature Chemistry, Volume 12, pgs. 26-35, published 11/25/2019), Chen et al. (Fusion protein linkers: Property, design, and functionality, Advanced Drug Delivery Reviews, Volume 65, Issue 10, pgs. 1357-1369, published 10/15/2013), and Sigl et al. (Programmable icosahedral shell system for virus trapping, Nature Materials, Volume 20, pgs. 1281-1289, published 6/14/2021).
Claims 1-5, 7-12, 21, and 22 of copending Application No. 17/612000 recite a structure for pattern-recognized targeting of diseases, comprising: an oligonucleotide scaffold including a plurality of binders incorporated into binder insertion regions, wherein the binder insertion regions are arranged to conform to a spatial pattern of a plurality of epitopes on a surface of a target, so that the binders are positioned to bind each epitope of the plurality of epitopes on the surface of the target according to the spatial pattern of the plurality of epitopes on the surface of the target.
Claims 1-5, 7-12, 21, and 22 of copending Application No. 17/612000 do not recite the artificial biopolymer complex as recited in claims 1, 3-9, 11, 13-21, and 25 of the instant application.
Regarding the claims of the copending application, the artificial biopolymer complex is taught by the combined teachings of Kwon, Chen, and Sigl, as described above.
One of ordinary skill in the art would have been motivated to use complex as taught by Kwon et al. in view of claims 1-5, 7-12, 21, 22 of copending Application No. 17/612000. Claims 1-5, 7-12, 21, 22 of copending Application No. 17/612000 recite a structure for pattern-recognized targeting of diseases, comprising: an oligonucleotide scaffold including a plurality of binders incorporated into binder insertion regions, and Kwon et al. teaches such a structure for pattern-recognized targeting of diseases, comprising: an oligonucleotide scaffold including a plurality of binders incorporated into binder insertion regions (See MPEP 2144.06: Substituting equivalents known for the same purpose).
One of ordinary skill in the art would have had a reasonable expectation of success for using complex as taught by Kwon et al. in view of claims 1-5, 7-12, 21, 22 of copending Application No. 17/612000. There would have been a reasonable expectation of success given the underlying materials and methods are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3-9, 11, 13-21, 25, and 37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-6, 8-18, 20 of copending Application No. 16/550323 in view of Kwon et al. (Designer DNA architecture offers precise and multivalent spatial pattern-recognition for viral sensing and inhibition, Nature Chemistry, Volume 12, pgs. 26-35, published 11/25/2019) in view of Chen et al. (Fusion protein linkers: Property, design, and functionality, Advanced Drug Delivery Reviews, Volume 65, Issue 10, pgs. 1357-1369, published 10/15/2013) in further view of Sigl et al. (Programmable icosahedral shell system for virus trapping, Nature Materials, Volume 20, pgs. 1281-1289, published 6/14/2021) and Chang et al. (US 8440811 B2, published 5/14/2013).
Claims 1, 3-6, 8-18, 20 of copending Application No. 16/550323 recite a method for potent diagnosing disease-causing entities (DCEs) or detecting disease specific protein marker using a deoxyribonucleic acid (DNA) nanostructure-based sensor and inhibitor, comprising:
(1) identifying and analyzing a pattern of a pathogenic surface ligand; (2) designing the DNA nanostructure that mirrors the pattern of the pathogenic surface ligand; (3) synthesizing or evolving a binder against a pathogenic domain to match the pathogenic surface ligand placement; (4) incorporating the binder at appropriate locations onto the DNA nanostructure to match the pathogenic surface ligand placement and spacing to form a multivalent DNA nanostructure-binder complex; (5) binding the multivalent DNA nanostructure-binder complex to the pathogenic surface ligand for sensing and inhibiting the disease, and (6) measuring and analyzing the resultant fluoresce light generated in binding step (5). It is noted that a method of using a product renders the product obvious.
Claims 1, 3-6, 8-18, 20 of copending Application No. 16/550323 do not recite the artificial biopolymer complex as recited in claims 1, 3-9, 11, 13-21, 25, and 37.
See the teachings of Kwon et al., Chen et al., Sigl et al., and Chang et al., as described above.
One of ordinary skill in the art would have been motivated to use complex as taught by Kwon et al., Chen et al., Sigl et al., and Chang et al., in view of claims 1, 3-6, 8-18, 20 of copending Application No. 16/550323. Claims 1, 3-6, 8-18, 20 of copending Application No. 16/550323 recite DNA nanostructure for diagnosing entities, and Kwon et al. teaches such a detection structure (See MPEP 2144.06: Substituting equivalents known for the same purpose).
One of ordinary skill in the art would have had a reasonable expectation of success for using complex as taught by Kwon et al. in view of claims 1, 3-6, 8-18, 20 of copending Application No. 16/550323. There would have been a reasonable expectation of success given the underlying materials and methods are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
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/D.T.Y./Examiner, Art Unit 1635
/RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635
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