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 .
Status of Claims/Rejections
Claims 34-55 are pending. The previous 102 rejections are withdrawn in light of the amendments and applicants remarks of 02/04/26. However, the double patenting rejections are upheld.
Obviousness Type 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.
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Claims 34-44, 47-52 and 55 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 11,007,245. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘007 are the following:
1. A method of synthesizing a capture agent to a target comprising the steps of: (a) selecting a linker to connect an anchor ligand to a secondary ligand, wherein the anchor ligand and the secondary ligand were previously determined to bind to the same target at different binding sites representing distinct epitopes, wherein the linker is selected based on the distance between the binding site of the anchor ligand and the binding site of the secondary ligand, wherein the anchor ligand and the secondary ligand bind their respective binding sites on the target in an orientation such that the target can promote 1,3-dipolar cycloaddition between an acetylene group on one of the anchor ligand or secondary ligand and an azide group on the other of the anchor ligand or secondary ligand to form a triazole linkage in the absence of a separate catalyst, wherein for the cycloaddition reaction one of the azide group or the acetylene group is connected to the anchor ligand or secondary ligand via the selected linker; and (b) synthesizing a capture agent comprising the anchor ligand, the secondary ligand, and the selected linker, thereby generating the capture agent, wherein the dissociation constant of the capture agent for binding to the target is lower than the dissociation constant of either the anchor ligand or the secondary ligand for binding to the target.
2. The method of claim 1, wherein the linker has a length that is within 10% of the distance between the anchor ligand and the secondary ligand when both ligands are bound to the target.
3. A method of synthesizing a capture agent for inhibiting SNAP-25 cleavage mediated by botulinum neurotoxin serotype A protein in one or more neurons, wherein the botulinum neurotoxin serotype A protein comprises a heavy chain and a light chain, wherein the light chain comprises an enzymatic active site, comprising (a) selecting an anchor ligand that specifically binds to the enzymatic active site of the botulinum neurotoxin serotype A protein; (b) selecting a secondary ligand that specifically binds at a distinct epitope from the anchor ligand within 5-10 angstroms on the botulinum neurotoxin serotype A protein; and (c) linking the anchor ligand and secondary ligand together, wherein the secondary ligand must bind to an epitope so that it specifically binds to an occluded conformation of the botulinum neurotoxin serotype A holotoxin, thereby synthesizing the capture agent for inhibiting SNAP-25 cleavage mediated by botulinum neurotoxin serotype A protein in one or more neurons.
4. The method of claim 3, wherein the linking of the anchor ligand and the secondary ligand is performed using a linker.
5. The method of claim 4, wherein the linker has a length that is between 100 and 110% of the distance between the anchor ligand and the secondary ligand when both ligands are bound to the botulinum neurotoxin serotype A protein.
6. A method of targeting adjacent epitopes on a single protein comprising (a) identifying an anchor ligand that binds to a first epitope and a secondary ligand that binds to a second epitope, wherein the first and second epitopes are adjacent on the single protein; (b) screening the anchor ligand and secondary ligand against a linker library based on affinity of the combined anchor ligand, linker and secondary ligand to bind the single protein; and (c) selecting a linker to connect the anchor ligand to the secondary ligand, thereby targeting adjacent epitopes of the single protein by generating a capture agent that targets adjacent epitopes on the single protein, wherein the dissociation constant of the capture agent for binding to the target protein is lower than the dissociation constant of either the anchor ligand or the secondary ligand for binding to the target protein.
7. The method of claim 6, wherein the adjacent epitopes are 5-10 angstroms apart on the single protein when the single protein is folded.
8. The method of claim 4, wherein the linker has a length that is between 100 and 110% of the distance between the anchor ligand and the secondary ligand when both ligands are bound to the first and second epitopes, respectively.
9. The method of claim 4, wherein the linker is a tripeptide.
10. The method of claim 4, wherein the anchor ligand, secondary ligand, or both, are linked to the linker via a 1,4-substituted-1,2,3-triazole residue (Tz4) or via a 1,5-substituted-1,2,3-triazole residue (Tz5).
11. The method of claim 1 further comprising, prior to selecting the linker, the steps of: (i) identifying an anchor ligand and a secondary ligand that bind to the same target peptide at distinct epitopes; (ii) identifying the binding sites of the anchor ligand and the secondary ligand on the target peptide; and (iii) calculating the distance between the binding site of the anchor ligand and the secondary ligand.
12. The method of claim 1, wherein the target is a protein.
13. The method of claim 1, wherein the anchor ligand is identified by binding to an epitope on the target.
14. The method of claim 1, wherein the secondary ligand is identified by binding to an epitope on the target.
15. The method of claim 1 further comprising, prior to selecting the linker, identifying the anchor ligand, the secondary ligand, and the binding sites of the anchor ligand and the secondary ligand on the target.
16. The method of claim 1 further comprising, prior to selecting the linker, calculating the distance between the binding site of the anchor ligand and the binding site of the secondary ligand.
17. The method of claim 1, wherein the capture agent further comprises a tertiary ligand.
Claims 1-9 meet all of the structural limitations of claims 34-40, 42-44, 47 and 50 (Teaching both ligands, a tripeptide linker, Tz4, Tz5, amide bonds, dissociation constant, etc.). Both have the same structure, and therefore the same inherent properties. Claims 48, 49 and 41 are met because ‘245 teach the same distance between ligands and angstroms (see claims 5, 7 and 8).
Claims 51, 52 and 55 are met because the claimed compound is a structure that is identical to the of the instant claims. As such, the binding capability, and specific dissociation constants are the same, as they are inherent.
Instant claims 45 and 46 are rendered obvious in view of Farrow, as discussed above, as this reference teaches the same tripeptide ligand and biotin as part of the same type of peptide structure.
Claims 34- 55 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 11,007,245 in view of Farrow et al. (See above).
Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims also require the tripeptide Leu-Aib-Gly, PEG and biotin, which are all taught and rendered obvious by Farrow. One would be motivated to make these modifications because they are all taught to have the same ligands, same dual epitopes and same antigen binding purposes. A such, there is a reasonable expectation of success that these modifications can be made to the same structure and effectively bind to the target ligand of interest.
Claims 34- 55 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 9,913,875. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘875 teach the following:
1. A capture agent comprising an anchor ligand that comprises a cyclic peptide comprising the formula of Dab(DNP)-R-Lys(N3)-T-Dab-Pra-L-SEQ ID NO:3).
2. The capture agent of claim 1, wherein the anchor ligand comprises a molecule of formula Inh-1 is absent or is a linker to the secondary ligand.
3. The capture agent of claim 1, further comprising a secondary ligand comprises a cyclic peptide comprising the formula of -Pra-NYRWL-Lys(N3) (SEQ ID NO:7).
4. The capture agent of claim 1, further comprising a secondary ligand comprises a molecule of formula Inh-1.
5. The capture agent of claim 1 further comprising a linker.
6. The capture agent of claim 5, wherein the linker is a tripeptide.
7. The capture agent of claim 6, wherein the linker comprises the amino acid sequence of Gly-Aib-Leu or Leu-Aib-Gly.
8. The capture agent of claim 7, wherein the linker comprises the amino acid sequence of Gly-Aib-Leu.
9. The capture agent of claim 7, wherein the linker comprises the amino acid sequence of Leu-Aib-Gly.
10. The capture agent of claim 5, wherein the linker comprises PEG.sub.4.
11. The capture agent of claim 5, wherein the anchor ligand and/or the secondary ligand are linked to the linker via a 1,4-substituted-1,2,3-triazole residue (Tz4) or via a 1,5-substituted-1,2,3-triazole residue (Tz5).
12. The capture agent of claim 11, wherein the anchor ligand is linked to the linker via a Tz4.
13. The capture agent of claim 1, wherein the capture agent comprises a molecule of formula Inh-2, wherein R3 is a capping group, or comprises a label or a spontaneously translocating peptide.
14. The capture agent of claim 13, wherein the label is selected from the group consisting of biotin, copper-DOTA, biotin-PEG3, aminooxyacetate, .sup.19FB, .sup.18FB, 5-carboxyfluorescein, and FITC-PEG3.
15. The capture agent of claim 13, wherein the label is a detectable moiety selected from the group consisting of .sup.64Cu DOTA, .sup.68Ga DOTA, .sup.68Ga NOTA, .sup.18F, Al.sup.18F NOTA, .sup.64Cu, .sup.68Ga .sup.89Zr, .sup.124I, .sup.86Y, .sup.94mTc, .sup.110mIn, .sup.11C and .sup.76Br.
16. The capture agent of claim 13, wherein the spontaneously translocating peptide comprises the amino acid sequence of pliylrllrGqf (SEQ ID NO:24).
Claims 1-16 meet all of the structural limitations of claims 34-40, 42-45, 47 and 50 (Teaching both ligands, a tripeptide linker, Tz4, Tz5, amide bonds, dissociation constant, etc.). Both have the same structure, and therefore the same inherent properties. Claims 41, 48 and 49 are met because the linker inherently must have the same distance where the same exact structure is taught. Claims 51-55 are met because ‘875 teaches the same epitopes, which inherently have the same binding ability to the same antigen with the same KD, and claim 13 of ‘875 teaches a translocating peptide. Claim 46 is met because claim 14 teaches PEG.
Claims 34- 55 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 11,723,944. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of ‘944 teach the following:
1. A capture agent to a target produced by a method comprising the steps of: (a) selecting a linker to connect an anchor ligand to a secondary ligand, wherein the anchor ligand and the secondary ligand bind to the same target at different binding sites representing distinct epitopes, wherein the linker is selected based on the distance between the binding site of the anchor ligand and the binding site of the secondary ligand, wherein the anchor ligand and the secondary ligand bind their respective binding sites on the target in an orientation such that the target can promote 1,3-dipolar cycloaddition between (i) an acetylene group on the anchor ligand and an azide group on the secondary ligand or (ii) an azide group on the anchor ligand and an acetylene group on the secondary ligand to form a triazole linkage in the absence of a separate catalyst, wherein for the cycloaddition reaction, either the azide group or the acetylene group is connected to the anchor ligand or the secondary ligand via the selected linker; (b) synthesizing a capture agent comprising the anchor ligand, the secondary ligand, and the selected linker, thereby generating the capture agent, wherein the dissociation constant of the capture agent for binding to the target is lower than the dissociation constant of either the anchor ligand or the secondary ligand for binding to the target.
2. The capture agent of claim 1, wherein the linker has a length that is within 10% of the distance between the anchor ligand and the secondary ligand when both ligands are bound to the target protein.
3. The capture agent of claim 1 further comprising, prior to selecting the linker, the steps of: (i) identifying an anchor ligand and a secondary ligand that bind to the same target peptide at distinct epitopes; (ii) identifying the binding sites of the anchor ligand and the secondary ligand on the target peptide; and (iii) calculating the distance between the binding site of the anchor ligand and the secondary ligand.
4. The capture agent of claim 1, wherein the target is a protein.
5. The capture agent of claim 1, wherein the anchor ligand is identified by binding to an epitope on the target.
6. The capture agent of claim 1, wherein the secondary ligand is identified by binding to an epitope on the target.
7. The capture agent of claim 1 further comprising, prior to selecting the linker, identifying the anchor ligand, the secondary ligand, and the binding sites of the anchor ligand and the secondary capture agent on the target.
8. The capture agent of claim 1 further comprising, prior to selecting the linker, calculating the distance between the binding site of the anchor ligand and the binding site of the secondary ligand.
9. The capture agent of claim 1, wherein the capture agent further comprises a tertiary ligand.
10. A capture agent targeting adjacent epitopes on a single protein produced by a method comprising (a) identifying an anchor ligand that binds to a first epitope and a secondary ligand that binds to a second epitope, wherein the first and second epitopes are adjacent on the single protein; (b) screening the anchor ligand and secondary ligand against a linker library based on affinity of the combined anchor ligand, linker and secondary ligand to bind the single protein; and (c) selecting a linker to connect the anchor ligand to the secondary ligand, thereby targeting adjacent epitopes of the single protein by generating a capture agent that targets adjacent epitopes on the single protein, wherein the dissociation constant of the capture agent for binding to the target protein is lower than the dissociation constant of either the anchor ligand or the secondary ligand for binding to the single protein.
11. The method of claim 10, wherein the adjacent epitopes are 5-10 angstroms apart on the single protein when the single protein is folded.
This meets the limitations of claims 34-43, 47-50 and 55 because claims 1-11 teach the same structural limitations, with the same linkers and angstroms, as well as the inherently lower dissociation constant. Instant claims 51, 52 and 55 are met because the claimed compound is a structure that is identical to the of the instant claims. As such, the binding capability to antigens, antigen properties, and specific dissociation constants are the same (See MPEP 2112).
Claims 34- 55 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 11,723,944 in view of Farrow et al. (See above). Instant claims 43-45, 53 and 54 are rendered obvious in view of Farrow et., as described above, because this reference teaches the same tripeptide ligand linkers, amide bonds and as part of the same type of biligand structure as ‘944. One would be motivated to make these modifications because they are all taught to have the same ligands, same dual epitopes and same antigen binding purposes. A such, there is a reasonable expectation of success that these modifications can be made to the same structure and effectively bind to the target ligand of interest.
Response to arguments/Remarks
Applicants have only responded that they would like the double patenting rejections to be held in abeyance, which does not overcome these rejections.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JEANETTE M LIEB whose telephone number is (571)270-3490. The examiner can normally be reached M-F 10-7.
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/JEANETTE M LIEB/Primary Examiner, Art Unit 1654