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 .
DETAILED ACTION
The examiner for this case has changed.
Election/Restrictions
Applicant’s election without traverse of “claims reciting complexes” in the reply filed on 04/07/2026 is acknowledged.
Claims 60-84 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 04/07/2026.
Applicant is reminded that upon the cancelation of claims to a non-elected invention, the inventorship must be corrected in compliance with 37 CFR 1.48(a) if one or more of the currently named inventors is no longer an inventor of at least one claim remaining in the application. A request to correct inventorship under 37 CFR 1.48(a) must be accompanied by an application data sheet in accordance with 37 CFR 1.76 that identifies each inventor by his or her legal name and by the processing fee required under 37 CFR 1.17(i).
Status of Claims
Claims 1-28 are cancelled.
Claims 29-84 are pending.
Claims 60-84 are withdrawn. It is noted by the examiner that claims 74, 79, and 84 recite in the preamble “the complex of…;” however, since these claims each depend from method claims they are being considered as method claims and not “claims reciting complexes.”
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The examiner finds support for all claimed limitations in the earliest filed non-provisional application no, 63133013, filed 12/31/2020.
Information Disclosure Statement
The information disclosure statement(s) (IDS) submitted on 09/29/2023 and 04/072026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 44 recites the limitation "a 5’-X-Y-X-3’ configuration" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. Claim 44 depends from claim 42 which depends from claim 41 which depends from claim 29. Claim 29 in lines 15-17 require the oligonucleotide to have a “5’-X-Y-Z-3’ configuration.” Furthermore, claim 44 in line 3 recites X, Y, and Z, which is inconsistent with the 5’-X-Y-X-3’ configuration recited in line 1.
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.
Claim 44 is 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. Claim 44 ultimately depends from claim 29, which requires the oligonucleotide to be 16 nucleotides in length. However, claim 44 recited configurations that are greater than 16 nucleotides in length. For example, in lines 4 and 10, claim 44 recites a 5-10-5 configurations that results in a 20-mers, and, in line 6, claim 44 recites a 5-10-4 configuration that results in a 19-mer, which fail to further limit claim 29 from which claim 44 depends. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 29-59 are rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-3 of US Patent No. 11,931,421. Although the claims at issue are not identical, they are not patentably distinct from each other because the complex recited in claims 1-3 of ‘421 is a species that falls squarely within the scope of the genus of complexes recited in instant claims 29-59.
With respect to the antibody component: Claim 1 of US 11,931,421 recites a Fab comprising a heavy chain of SEQ ID NO: 19 and a light chain of SEQ ID NO: 20. These correspond to SEQ ID NO: 101 and SEQ ID NO: 90, respectively, of the instant application, see sequence alignments below. A heavy chain comprising SEQ ID NO: 101 and a light chain comprising SEQ ID NO: 90 necessarily and inherently comprise CDR-H1 of SEQ ID NO: 33, CDR-H2 of SEQ ID NO: 34, CDR-H3 of SEQ ID NO: 35, CDR-L1 of SEQ ID NO: 36, CDR-L2 of SEQ ID NO: 37, and CDR-L3 of SEQ ID NO: 32, as recited in instant claim 29. Accordingly, the Fab of claim 1 of ‘421 is a species falling within the genus of anti-TfR1 antibodies defined by CDR sequences in instant claim 29 and the VH/VL sequences of instant claim 30, and is identical to the Fab recited in the instant claims.
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With respect to the oligonucleotide component: Formula (Ic) of claim 1 of ‘421 comprises the same oligonucleotide as SEQ ID NO: 214 of the instant application, which is the same nucleobase sequence as SEQ ID NO: 179 with the specified sugar modifications and phosphorothioate internucleoside linkages, and which is antisense to SEQ ID NO: 166. This oligonucleotide is 16 nucleotides in length and comprises a 5’-X-Y-Z-3’ gapmer configuration of LLEE-(D)8-EELL, satisfying all structural limitations recited in the instant claims. Accordingly, the oligonucleotide of Formula (Ic) in claim 1 of ‘421 is identical to the oligonucleotide limitations of the instant claims. See sequence search results in the file wrapper for SEQ ID NO: 21 of ‘421.
With respect to the linker and overall complex structure: The complex of Formula (Ic) in claim 1 of US ‘421 comprises the same antibody-oligonucleotide conjugate structure recited in the instant claims, including the bicyclononyne-triazole click chemistry conjugation, the polyethylene glycol spacer, and the valine-citrulline-para-aminobenzylcarbamate protease-cleavable linker, wherein n=3 and m=4. The instant claims encompass this same complex without reciting the specific linker lengths within the overall linker structure, and therefore are broader in scope but not patentably distinct, as the linker of ‘421 is a species of the linker formula as instantly claimed. Therefore, the antibody-linker-oligonucleotide combination of the instant claims is anticipated by ‘421.
Claims 29-59 are rejected on the grounds of nonstatutory double patenting as being unpatentable over claims 1-3 of US Patent No. 12,440,574. Although the claims at issue are not identical, they are not patentably distinct from each other because the complex recited in claims 1-3 of ‘574 constitutes a fixed species that falls within the scope of the genus of complexes recited in instant claims 29-59.
With respect to the antibody component: Claim 1 of ‘574 recites a Fab comprising a heavy chain of SEQ ID NO: 19 and a light chain of SEQ ID NO: 20, which correspond to SEQ ID NO: 101 and SEQ ID NO: 90 of the instant application, respectively, see sequence alignments above. A heavy chain comprising SEQ ID NO: 101 and a light chain comprising SEQ ID NO: 90 necessarily and inherently comprises CDR-H1 of SEQ ID NO: 33, CDR-H2 of SEQ ID NO: 34, CDR-H3 of SEQ ID NO: 35, CDR-L1 of SEQ ID NO: 36, CDR-L2 of SEQ ID NO: 37, and CDR-L3 of SEQ ID NO: 32 as recited in instant claim 29, and VH of SEQ ID NO: 76 and VL of SEQ ID NO: 75 as recited in instant claim 30. The Fab of claim 1 of ‘574 is therefore identical to the antibody component recited in instant claims 32-34, 54, and 56, and is a species within the genus of anti-TfR1 antibodies defined by CDR sequences in instant claim 29 and VH/VL sequences in instant claim 30.
With respect to the oligonucleotide component: The oligonucleotide of Formula (Ib) in claim 1 of ‘574 comprises the nucleobase sequence CAGCGCCCACCAGUCA (SEQ ID NO: 21 of US 12,440,574), which is identical to SEQ ID NO: 179 of the instant application and antisense to SEQ ID NO: 166 of the instant application. Furthermore, the specific sugar modification pattern of Formula (Ib) comprising a 5’-LLEE-(D)8-EELL-3’ gapmer configuration with 5-methyl-2’-MOE-cytidine, 5-methyl-2’-4’-bicyclic-cytidine, 5-methyl-2’-MOE-uridine, and phosphorothioate internucleoside linkages throughout is identical to the structure recited in the instant claims and SEQ ID NO: 214 claimed in the instant application. The oligonucleotide of Formula (Ib) is therefore identical to the oligonucleotide recited in the instant claims. See sequence search results in the file wrapper.
With respect to the linker and overall complex structure: Instant claims 50-57 recite the antibody-linker-oligonucleotide complex at the genus level, wherein the linker component L1 is defined as a Markush group encompassing substituted or unsubstituted aliphatic, heteroaliphatic, carbocyclylene, heterocyclylene, arylene, heteroarylene, and various heteroatom-containing linking groups, and wherein n and m are variable integers. Formula (Ib) of claim 1 of ‘574 constitutes a fixed species within this genus, wherein every variable of the linker is resolved to a specific value, a specific bicyclononyne-triazole click chemistry conjugation unit, a specific polyethylene glycol spacer, a specific valine-citrulline-para-aminobenzylcarbamate protease-cleavable unit, with n=3 and m=4. Because the patented species of Formula (Ib) falls squarely within the scope of the genus linker recited in the instant claims, the claims are not patentably distinct.
Claims 29-59 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-17 of copending Application No. 18/856,247. Although the claims at issue are not identical, they are not patentably distinct from each other because the complexes recited in claims 1-17 of ‘247 and the instant claims 29-59 are directed to patentably indistinct subject matter.
Claims 7-9 of ‘247 recite compositions comprising a plurality of complexes of Formula (Ia), (Ib), and (Ic), respectively, each comprising an anti-TfR1 antibody whose CDR sequences (SEQ ID NOs: 7-10, 5, and 6 of Application No. 18/856,247) correspond to SEQ ID NOs: 33-37 and 32 of the instant application, respectively, see sequence search results in the file wrapper. Claim 15 of ‘247 further specifies that the heavy chain comprises SEQ ID NO: 19 and the light chain comprises SEQ ID NO: 20, corresponding to SEQ ID NOs: 101 and 90 of the instant application (see alignments above), thereby satisfying all antibody limitations of the instant claims. The oligonucleotide of Formula (Ib) and (Ic), and claim 6 of ‘247 comprises the nucleobase sequence CAGCGCCCACCAGUCA (SEQ ID NO: 21 of ‘247, corresponding to SEQ ID NO: 179 of the instant application) with the identical sugar modification pattern and phosphorothioate internucleoside linkages as SEQ ID NO: 214 of the instant application, satisfying the oligonucleotide limitations of the instant claims.
The instant claims differ from claims 1-17 of ‘247 in that they do not recite the K188/K190 conjugation site specificity limitation (at least 80% of light chain constant regions conjugated at K188 and/or K190). The instant claims are therefore broader than the claims of ‘247 in this respect. A claim that omits a limitation present in an otherwise identical reference claim is an obvious broadening of that reference claim. A person of ordinary skill in the art would have recognized that the same underlying complex could be produced and characterized without imposing or reciting a conjugation site distribution requirement, and that omitting such a manufacturing specificity limitation does not confer patentable distinction when the core complex structure is identical. Accordingly, the instant claims anticipated claims 1-17 of ‘247.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 29-59 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-10, and 14 of copending Application No. 18/856,264. Although the claims at issue are not identical, they are not patentably distinct from each other because the complex recited in the claims of ‘264 defines a genus within which the complexes of instant claims 29-59 are patentably indistinct species.
Regarding the formulation claims 1-2, 4-10, and 14 of ‘264, formulating the complex of the instant claims with Tris and sucrose would have been obvious to one of ordinary skill in the art because Tris buffer and sucrose are well-known and widely used excipients for formulating biologic therapeutics including antibody conjugates, and their selection for formulating an antibody-oligonucleotide conjugate represents routine pharmaceutical formulation practice requiring no inventive step beyond what is taught by the instant claims.
The instant claims teach the specific anti-TfR1 Fab-oligonucleotide complex in detail. Claim 27 of ’264 would have been obvious over the instant claims because broadening from a specific disclosed species, that is the particular anti-TfR1 Fab with defined CDR sequences and gapmer oligonucleotide sequence and modifications, to a generic class of Fab-gapmer conjugates linked via Formula (Ia) is an obvious generalization that a person of ordinary skill in the art would have been motivated to make, recognizing that the Formula (Ia) linker architecture is applicable to Fabs and gapmers generally and not limited to any particular antibody or oligonucleotide sequence.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 29-59 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 24-27 of copending Application No. 19/306,247. Although the claims at issue are not identical, they are not patentably distinct from each other because the complex recited in claim 24 of ‘247 constitutes a fixed species that falls within the scope of the genus of complexes recited in instant claims 29-59.
Claim 24 of Application No. ‘247 recites a complex comprising Formula (Id), wherein the oligonucleotide comprises the nucleobase sequence CAGCGCCCACCAGUCA (SEQ ID NO: 21 of ‘247, corresponding to SEQ ID NO: 179 of the instant application with the identical 5’-LLEE-(D)8-EELL-3’ gapmer sugar modification pattern and phosphorothioate internucleoside linkages as SEQ ID NO: 214 of the instant application, thereby satisfying all oligonucleotide limitations of the instant claims. The Fab of claim 24 of ‘247 comprises a heavy chain of SEQ ID NO: 19 and a light chain of SEQ ID NO: 20, corresponding to SEQ ID NOs: 101 and 90, respectively, of the instant application, see alignments above. This Fab necessarily and inherently comprises CDR-H1 of SEQ ID NO: 33, CDR-H2 of SEQ ID NO: 34, CDR-H3 of SEQ ID NO: 35, CDR-L1 of SEQ ID NO: 36, CDR-L2 of SEQ ID NO: 37, and CDR-L3 of SEQ ID NO: 32 and the VH SEQ ID NO: 76 and VL SEQ ID NO: 75 of the instant application, satisfying all antibody limitations of the instant claims.
The instant claims differ from claim 24 of ‘247 primarily in that instant claims 50-57 recite the linker component L1 at the genus level as a broad Markush group encompassing substituted or unsubstituted aliphatic, heteroaliphatic, carbocyclylene, heterocyclylene, arylene, heteroarylene, and various heteroatom-containing linking groups with variable n and m, whereas Formula (Id) of claim 24 of ‘247 constitutes a fixed species within that genus, wherein every variable of the linker is resolved to a specific value. Therefore, the antibody-linker-oligonucleotide complex of ‘247 is a species and anticipates the complexes in the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 29-59 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 24-27 of copending Application No. 19/306,199. Although the claims at issue are not identical, they are not patentably distinct from each other because the complex recited in claim 24 of ‘199 constitutes a fixed species that falls within the scope of the genus of complexes recited in instant claims 29-59.
Claim 24 of Application No. ‘199 recites a complex comprising Formula (Id), wherein the oligonucleotide comprises the nucleobase sequence CAGCGCCCACCAGUCA (SEQ ID NO: 21 of ‘199, corresponding to SEQ ID NO: 179 of the instant application with the identical 5’-LLEE-(D)8-EELL-3’ gapmer sugar modification pattern and phosphorothioate internucleoside linkages as SEQ ID NO: 214 of the instant application, thereby satisfying all oligonucleotide limitations of the instant claims. The Fab of claim 24 of ‘199 comprises a heavy chain of SEQ ID NO: 19 and a light chain of SEQ ID NO: 20, corresponding to SEQ ID NOs: 101 and 90, respectively, of the instant application, see alignments above. This Fab necessarily and inherently comprises CDR-H1 of SEQ ID NO: 33, CDR-H2 of SEQ ID NO: 34, CDR-H3 of SEQ ID NO: 35, CDR-L1 of SEQ ID NO: 36, CDR-L2 of SEQ ID NO: 37, and CDR-L3 of SEQ ID NO: 32 and the VH SEQ ID NO: 76 and VL SEQ ID NO: 75 of the instant application, satisfying all antibody limitations of the instant claims.
The instant claims differ from claim 24 of ‘199 primarily in that the instant claims recite the linker component L1 at the genus level as a broad Markush group encompassing substituted or unsubstituted aliphatic, heteroaliphatic, carbocyclylene, heterocyclylene, arylene, heteroarylene, and various heteroatom-containing linking groups with variable n and m, whereas Formula (Id) of claim 24 of ‘199 constitutes a fixed species within that genus, wherein every variable of the linker is resolved to a specific value. Therefore, the antibody-linker-oligonucleotide complex of ‘199 is a species and anticipates the complexes in the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to COREY LANE BRETZ whose telephone number is (571)272-7299. The examiner can normally be reached M-F 7:30am - 6:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ram Shukla can be reached at (571) 272-0735. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/COREY LANE BRETZ/Examiner, Art Unit 1635
/RAM R SHUKLA/Supervisory Patent Examiner, Art Unit 1635
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