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 .
Response to Amendment
Applicant’s amendments to the claims overcome rejections under 35 USC 112(a) previously set forth in the Non-Final Rejection.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 3-5 and 8 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 2 (independent claim as amended) recites several VHH molecules each comprising three CDRs. Claims 3-5 and 8 depend from claim 2 and recite full-length VHH amino acid sequences; however some of the full-length VHH sequences recited do not include any of the CDR combinations recited in claim 2. For example, the amino acid sequences of SEQ ID NOs: 273, 276-280, 423, 425, 430, 441, 443, 445, 447, 449, and 451 comprise the CDR combination of SEQ ID NOs: 5, 6, and 7, which are not recited in claim 2. The amino acid sequences of SEQ ID NOs: 130-149 and 252-271 comprise the CDR combination of SEQ ID NOs: 1, 2, and 3. The amino acid sequence of SEQ ID NOs: 250 and 274 comprise the prohibited CDR combination of SEQ ID NOs: 17, 73, and 3. As such, claims 3-5 and 8 encompass embodiments that do not incorporate the limitations of claim 2. Thus, claims 3-5 and 8 fail to further limit claim 2, but rather broadens the claim scope. The above-identified sequences are provided as representative examples and are not intended to constitute an exhaustive identification of every VHH molecule that fails to satisfy the dependency requirement. Applicant is required to review that the full-length VHH sequences identified in the dependent claims and ensure each VHH sequence comprises one of the CDR combinations recited in claim 2, or otherwise amend the claims to establish proper dependency. 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 2-20 and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16-35 of copending Application No. 19495916 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending claims either anticipate or are obvious variants over the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The co-pending claims recite a conjugate comprising (i) one or more VHH molecule(s) of formula FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4, and (ii) at least one therapeutic compound or vehicle comprising said therapeutic compound, wherein said VHH molecule binds at the surface of a cell of the nervous system (e.g. a brain or spinal cord cell) with an affinity of 0.1 nM to 2500 nM and comprises the CDR combinations recited in instant claim 2 (co-pending claims 16, 24, 25, and 26). A conjugate compound would necessarily comprise a covalent/noncovalent bond or linker between the components of the conjugate. The VHH molecule can comprise i) an amino acid sequence selected from SEQ ID NOs: 678, 682, 694, 703, 273, 276-284, 412, 415, 418, 421, 423, 425, 428, 430, 433, 436, 439, 441,443,445, 447,449,451,454, 457, 677, 702 (corresponding to respective SEQ ID NOs: recited in instant claim 3) (co-pending claim 17); ii) an amino acid sequence selected from SEQ ID NOs: 242-271, 274, 275, 675, 676, and 701 (corresponding to respective SEQ ID NOs in instant claim 4) (co-pending claim 18); iii) an amino acid sequence selected from SEQ ID NOs: 285-299 (corresponding to SEQ ID NOs of instant claim 5) (co-pending claim 19); iv) an amino acid sequence selected from SEQ ID NOs: 613-615 (corresponding to respective SEQ ID NOs: recited in instant claim 6) (co-pending claim 20); or v) an amino acid sequence selected from SEQ ID NOs: 252-271, and 273-275 (corresponding to respective SEQ ID NOs recited in instant claim 8 (co-pending claims 17 and 18). The VHH molecule further comprises a tag and/or linker (co-pending claim 21). The VHH molecule can be humanized (co-pending claim 22) and bind to human, non-human, and/or rodent transferrin receptor (TfR) (co-pending claim 23). The therapeutic compound can be a peptide, polypeptide, protein, antibody, or nucleic acid (co-pending claim 27). The nucleic acid is mRNA, a ribozyme, or an oligonucleotide selected from single stranded/double stranded siRNA, saRNA, gapmer, antisense oligonucleotide, shRNA, miRNA, aptamer RNA, or bridged nucleic acid (co-pending claim 28). The conjugate can further comprise at least one additional compound selected from a half-life extending moiety, stabilizing group, or scaffold (co-pending claim 29). The half-life extending moiety, stabilizing group, or scaffold is an antibody, VHH molecule, PEG, serum albumin protein, serum albumin binding moiety, Fc fragment, or Fc heterodimer comprising a modified Fc having the sequence of SEQ ID NO: 664 on the knob arm, or a modified Fc having a sequence of SEQ ID NO: 665 on the hole arm (co-pending claim 30). The amino acid sequences of SEQ ID NOs: 664 and 665 correspond to SEQ ID NOs 664 and 665 of the instant claims. Further recited is a pharmaceutical composition comprising the conjugate compound and a pharmaceutically acceptable support, carrier, or excipient (co-pending claim 31) as well as a method for treating a nervous system disease, including those specifically recited in instant claim 22 (co-pending claims 31, 32, 34, and 35).
Thus, the co-pending claims meet the limitations of instant claims 2-20 and 22.
Claims 2-20, and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 16-34 of copending Application No. 19495834 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the co-pending claims either anticipate or are obvious variants over the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The co-pending claims recite a conjugate comprising (i) one or more VHH molecule(s) of formula FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4, and (ii) one or more oligonucleotide(s), wherein said VHH molecule binds human, non-human, and/or rodent transferrin receptor (TfR) at the surface of a muscle cell and comprises the CDR combinations recited in instant claim 2 (co-pending claims 16 and 23). The minimal structure required for the VHH chains to bind to a cell of the CNS (e.g. brain or spinal cord cell) with an affinity of 0.1 nM to 2500 nM are the CDR recited in the instant claims. Thus, the VHH chains of the co-pending claims having the same structure (i.e. CDRs) also possess these functional properties. Further, a conjugate compound would necessarily comprise a covalent/noncovalent bond or linker between the components of the conjugate. The VHH molecule can comprise i) an amino acid sequence selected from SEQ ID NOs: 678, 682, 694, 703, 273, 276-284, 412, 415, 418, 421, 423, 425, 428, 430, 433, 436, 439, 441,443,445, 447,449,451,454, 457, 677, 702 (corresponding to respective SEQ ID NOs: recited in instant claim 3) (co-pending claim 17); ii) an amino acid sequence selected from SEQ ID NOs: 242-271, 274, 275, 675, 676, and 701 (corresponding to respective SEQ ID NOs in instant claim 4) (co-pending claim 18); iii) an amino acid sequence selected from SEQ ID NOs: 285-299 (corresponding to SEQ ID NOs of instant claim 5) (co-pending claim 19); iv) an amino acid sequence selected from SEQ ID NOs: 613-615 (corresponding to respective SEQ ID NOs: recited in instant claim 6) (co-pending claim 20); or v) an amino acid sequence selected from SEQ ID NOs: 252-271, and 273-275 (corresponding to respective SEQ ID NOs recited in instant claim 8 (co-pending claims 17 and 18). The VHH molecule further comprises a tag and/or linker (co-pending claim 21). The VHH molecule can be humanized (co-pending claim 22). The oligonucleotide is selected from a siRNA, saRNA, gapmer, antisense oligonucleotide (ASO), shRNA, miRNA, aptamer RNA, and bridged nucleic acid (BNA) (co-pending claim 24). The conjugate can further comprise at least one additional compound selected from a half-life extending moiety, stabilizing group, or scaffold (co-pending claims 26 and 27). The half-life extending moiety, stabilizing group, or scaffold is an antibody, VHH molecule, PEG, serum albumin protein, serum albumin binding moiety, Fc fragment, or Fc heterodimer comprising a modified Fc having the sequence of SEQ ID NO: 664 on the knob arm, or a modified Fc having a sequence of SEQ ID NO: 665 on the hole arm. The amino acid sequences of SEQ ID NOs: 664 and 665 correspond to SEQ ID NOs 664 and 665 of the instant claims (co-pending claim 28). Further recited is a pharmaceutical composition comprising the conjugate compound and a pharmaceutically acceptable support, carrier, or excipient (co-pending claim 29) as well as a method for treating a muscular dystrophy such as ALS in a subject (co-pending claims 30, 33, and 34).
Thus, the co-pending claims meet the limitations of instant claims 2-20 and 22.
Response to Arguments
Applicant's arguments filed 06/12/2026 have been fully considered but they are not persuasive with respect to the rejection under 35 USC 112(d) and double patenting.
With respect to the 35 USC 112(d) rejection, Applicant argues that the claims have been amended to render the rejection moot. In response to Applicant’s argument, the Examiner notes that claim 2 (independent claim as amended) recites several VHH molecules each comprising three CDRs. Claims 3-5 and 8 depend from claim 2 and recite full-length VHH amino acid sequences; however some of the full-length VHH sequences recited do not include any of the CDR combinations recited in claim 2. Applicant is required to review that the full-length VHH sequences identified in the dependent claims and ensure each VHH sequence comprises one of the CDR combinations recited in claim 2, or otherwise amend the claims to establish proper dependency.
With respect to the double patenting rejections, Applicant argues the co-pending applications ‘916 and ‘834 have later effective filing dates and should thus be withdrawn because they are the only remaining rejections left. In response to Applicant’s arguments, the Examiner notes that the 35 USC 112(d) rejection was not addressed/overcome by amendment; as such, the double patenting rejections are not the only remaining issues. Thus, the double patenting rejections are maintained.
Conclusion
No claims are allowable.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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/LIA E TAYLOR/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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