DETAILED ACTION
Claims 1-6, 19-24 and 29-33 were/stand cancelled. Claims 7-13, 25 and 34 were amended. Claims 7-18, 25-28 and 34-36 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I and structure 1 in the reply filed on July 9 2026 is acknowledged. Claims 7-18, 25-28 and 34-36 are pending in the application. Claims 34-36 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on July 9 2026. Accordingly, claims 7-18 and 25-28 are being examined on the merits herein.
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application is a CON of 16/759,610 (04/27/2020; PAT 11,597,701) which is a 371 of PCT/US18/58471 (10/31/2018) which claims benefit of 62/679,549 (06/01/2018) and claims benefit of 62/646,739 (03/22/2018) and claims benefit of 62/580,398 (11/01/2017) as reflected in the filing receipt issued November 28 20223.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on September 22 2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 7-17 and 25-28 are rejected under 35 U.S.C. 103 as being unpatentable over Holzemann et al. (US Patent No. 6576637) in view of Deming et al. (WO0194379) and Juliano et al. (Theranostics, 2011).
Applicant Claims
The instant application claims an αvβ6 integrin ligand. As elected the ligand is:
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Determination of the Scope and Content of the Prior Art
(MPEP §2141.01)
Holzemann et al. is directed to β-alanine derivatives. Claimed is a compound of formula I:
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wherein Q1-Q4 can be CH, R1 is A which is a C1 alkyl, n is 4, R2 is H, R6 is H and R3 can be:
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wherein R4 is H and Ar is aryl (claim 1). Ar can be naphthyl (column 6, lines 6-12). Claimed compounds include 4-methylpyridin-2-ylamino which corresponds to A being a C1 alkyl (aka methyl) and Q1-Q4 being CH (claims). A specific compound taught is: 3-{2-[4-(4-methylpyridin-2-ylamino)butyrylamino]acetylamino}-3-(4-naphthalen-1-ylphenyl)propionic acid which differs from the instant claims in the length of n (3 vs claimed 4) and silence to the stereochemistry as well as PEG group (example 23).
Ascertainment of the Difference Between Scope the Prior Art and the Claims
(MPEP §2141.02)
While Holzemann et al. teach an integrin ligand which is similar in scope to the instant claims, Holzemann et al. does not teach attachment to an oligonucleotide or an ethylene glycol group attached. However, these deficiencies are cured by Deming et al. and Juliano et al.
Deming et al. is directed to methods and compositions for controlled polypeptide synthesis. It is taught that one approach to producing nonionic water-soluble polypeptides employs polyethylene glycol (PEG) which is typically grafted onto polypeptides or other polymers to improve their properties in vivo. PEG is nonionic, water-soluble and most importantly not recognized by immune systems. It is believed that PEG imports biocompatibility though formation of hydrated “steric barrier” at the surface of material that cannot be penetrated or recognized by biological molecules such as proteolytic enzymes. Despite its attractive properties, a drawback is the need for expensive amino-or-carboxylato-functionalized molecules for coupling (page 6; 12; 24). Taught are the use of oilgo (ethylene glycol) functionalized amino acids and their subsequence polymerization into oligo(ethylene glycol) functionalized polypeptides. The method of making these monomers includes the step of combining an ethylene glycol derivative with an amino acid having a reactive size group, such as serine. This results in an EG derivative of formula (CH3OCH2CH2)nX where n is about 1 to 3 EG repeats. A generalized scheme is shown in Scheme 1:
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(pages 20-21). Attachment of the peptide to functional groups such as oligonucleotides is taught (page 27; claim 14).
Juliano et al. is directed to integrin targeted delivery of gene therapeutics. Antisense and siRNA oligonucleotides have tremendous potential as therapeutic agents in cancer and other diseases. However, the effective delivery of these molecules to their intracellular site of action remains a key impediment. Members of the integrin family of cell surface adhesion receptors seem particularly attractive target for enhancing the efficiency and selectivity of delivery of antisense and siRNA oligonucleotides. Taught is direct conjugation between oligonucleotide and integrin targeting ligands. This direct conjugation allows enhanced cellular uptake. Bivalent RGD was conjugated (page 211-213).
Finding of Prima Facie Obviousness Rationale and Motivation
(MPEP §2142-2143)
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Holzemann et al., Deming et al. and Juliano et al. and replace the glycine of Holzmann et al. with the ethylene glycol derivatized amino acid of Deming et al., specifically structure A. One skilled in the art would have been motivated to replace the glycine to afford the benefits of a PEG group as taught by Deming et al. Since both the glycine of Holzmann et al. and Deming et al. would be coupled to other amino acids in the same manner, there is a reasonable expectation of success in simple substitution of one amino acid with another. Since PEG attachment not only provides for a point of attachment to other groups but also other benefits as taught by Deming et al. one skilled in the art would have been motivated to make the substitution. This results in structure 1a/1 claimed in claim 7-8.
Regarding the claimed stereochemistry, Holzman et al. teaches that the compounds have at least one chiral center and can therefore occur in several stereoisomeric forms. All these forms are included in the formula (column 4, lines 41-46).
Regarding the claimed cargo molecule, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Holzemann et al., Deming et al. and Juliano et al. and conjugate the peptide of Holzemann et al. to an oligonucleotide. One skilled in the art would have been motivated to conjugate an oligonucleotide to the peptide in order to afford targeted delivery of the oligonucleotide as taught by Juliano et al. Since Juliano et al. teaches the peptide can be directly conjugated to the oligonucleotide and PEG is a group which can be utilized to conjugate groups and Deming et al. teaches that oligonucleotides can be conjugated to the peptide, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Holzemann et al., Deming et al. and Juliano et al. and conjugate the oligonucleotide through the PEG group.
Regarding claim 11, Juliano et al. teaches an antisense oligonucleotide and siRNA reading on an RNAi agent.
Regarding claim 13, the instant specification provides no limiting definition of linking group and scaffold, therefore the use of the PEG reads on both linking group and scaffold which then binds the ligand of claim 7 to the cargo.
Regarding claims 14-17, as suggested by Juliano et al. the integrin ligand is used to target the oligonucleotide. Juliano et al. even suggests bivalent peptides which can be attached to oligonucleotides. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Holzemann et al., Deming et al. and Juliano et al. and vary the number of integrin ligands attached in order to achieve the desired level of targeting.
Regarding claim 25, Holzmann et al. exemplifies pharmaceutical compositions such as solutions.
Regarding claims 25-28, Holzmann et al. suggest the same ligand except for the PEG group and the oligonucleotide. Juliano et al. teaches an antisense oligonucleotide or siRNA. Since claims 25-28 are directed to the capabilities of the instantly claimed structure and the prior art suggests the claimed structure, the claims do not structurally distinguish from the instant claims.
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 7-13, 16, 18 and 25-28 are rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 12655428. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant application claims an αvβ6 integrin ligand. As elected the ligand is:
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Patent ‘428 claims an RNAi agent wherein the RNAi agent is linked to a target of the following formula.
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Thus, attachment of this target to the RNAi results in the same structure 1/1a wherein the cargo molecule is an RNAi. Administration to treat a respiratory disease is claimed.
Therefore, the scope of the patent claims and the instant application overlap and thus they are obvious variants of one another.
Claims 7-13, 16, 18 and 25-28 are rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 12486502. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
The instant claims are set forth above.
Patent ‘502 claims an RNAi agent for inhibition expression of a Receptor for Advanced Glycation End-products gene. As claimed, the RNAi includes the nucleotide sequence and a ligand which is of the following structure:
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Introduction into a cell is claimed.
Thus, attachment of this target to the RNAi results in the same structure 1/1a wherein the cargo molecule is an RNAi.
Therefore, the scope of the patent claims and the instant application overlap and thus they are obvious variants of one another.
Claims 7-13, 16, 18 and 25-28 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-61 of copending Application No.19707992. Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The instant claims are set forth above.
Copending ‘992 claims an RNAi agent wherein the RNAi agent is linked to a target of the following formula.
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Thus, attachment of this target to the RNAi results in the same structure 1/1a wherein the cargo molecule is an RNAi. Compositions are claimed. Administration to treat a respiratory disease is claimed.
Therefore, the scope of the copending application and the instant application overlap and thus they are obvious variants of one another.
Claims 7-13, 16, 18 and 25-28 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1, 5, 6, 11, 17-18, 20-21, 23-24, 26, 30-32 and 37 of copending Application No.19394336 (USPGPUB NO. 20260193655). Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The instant claims are set forth above.
Copending ‘336 claims an RNAi agent for inhibition expression of a Receptor for Advanced Glycation End-products gene. As claimed, the RNAi includes the nucleotide sequence and a ligand which is of the following structure:
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Compositions are claimed.
Thus, attachment of this target to the RNAi results in the same structure 1/1a wherein the cargo molecule is an RNAi.
Therefore, the scope of the copending application and the instant application overlap and thus they are obvious variants of one another.
Claims 7-13, 16, 18 and 25-28 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1, 6, 8-9, 11, 17-18, 20, 23, 25, 26, 28, 31,33, 37-39, 48, 52 and 47 of copending Application No.18791757 (USPGPUB NO: 20240392292). Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The instant claims are set forth above.
Copending ‘757 claims an RNAi agent wherein the RNAi agent is linked to a target of the following formula.
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Thus, attachment of this target to the RNAi results in the same structure 1/1a wherein the cargo molecule is an RNAi. Compositions are claimed. Administration to treat a respiratory disease is claimed.
Therefore, the scope of the copending application and the instant application overlap and thus they are obvious variants of one another.
Claims 7-13, 16, 18 and 25-28 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1, 5, 6-8, 13-17, 19, 23-24, 27, 30, 32, 35, 38, 42 and 47 of copending Application No.19287091 (USPGPUB NO: 20260022379). Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The instant claims are set forth above.
Copending ‘091 claims an RNAi agent wherein the RNAi agent is linked to a target of the following formula.
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Thus, attachment of this target to the RNAi results in the same structure 1/1a wherein the cargo molecule is an RNAi. Compositions are claimed. Administration to treat a respiratory disease is claimed.
Therefore, the scope of the copending application and the instant application overlap and thus they are obvious variants of one another.
Claims 7-13, 16, 18 and 25-28 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1, 6, 8-9, 11, 17-18, 20-21, 23-24, 26, 30-31, 34-36, 45, 49 and 52 of copending Application No.19299635 (USPGPUB NO: 20260043029). Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The instant claims are set forth above.
Copending ‘635 claims an RNAi agent wherein the RNAi agent is linked to a target of the following formula.
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Thus, attachment of this target to the RNAi results in the same structure 1/1a wherein the cargo molecule is an RNAi. Compositions are claimed. Administration to treat a respiratory disease is claimed.
Therefore, the scope of the copending application and the instant application overlap and thus they are obvious variants of one another.
Claims 7-13, 16, 18 and 25-28 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1, 6, 8-9, 11, 17-18, 20-21, 23-24, 26, 30-31, 34-36, 40, 42 and 46 of copending Application No.19266598 (USPGPUB NO: 20260078375). Although the conflicting claims are not identical, they are not patentably distinct from each other because both sets of claims overlap in scope.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The instant claims are set forth above.
Copending ‘598 claims an RNAi agent wherein the RNAi agent is linked to a target of the following formula.
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Thus, attachment of this target to the RNAi results in the same structure 1/1a wherein the cargo molecule is an RNAi. Compositions are claimed. Administration to treat a respiratory disease is claimed.
Therefore, the scope of the copending application and the instant application overlap and thus they are obvious variants of one another.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ABIGAIL VANHORN whose telephone number is (571)270-3502. The examiner can normally be reached M-Th 6 am-4 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Neil Hammell can be reached on 571-270-5919. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ABIGAIL VANHORN/Primary Examiner, Art Unit 1636
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