The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-279 are canceled. Claims 280-299 are pending and under consideration.
Priority: This application is a CON of U.S. Application 18502473, filed November 6, 2023, abandoned, which is a CON of U.S. Application 17868077, filed July 19, 2022, abandoned, which is a CON of U.S. Application 17015011, filed September 8, 2020, now U.S. Patent 11426466, which is a CON of PCT/US2019/021474, filed March 8, 2019, which claims priority to provisional applications 62/640168, filed March 8, 2018, 62/640188, filed March 8, 2018, 62/640194, filed March 8, 2018, and 62/756889, filed November 7, 2018.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 280-299 are rejected under 35 U.S.C. 103 as being unpatentable over Mrsny (US 7713737). Mrsny discloses a delivery construct comprising a receptor binding domain; a transcytosis domain; a peptide, polypeptide or protein to be delivered to a subject; and a cleavable linker, and compositions comprising the delivery construct (at least col. 91 claim 1, col. 94 claim 28). It is disclosed that the receptor binding domain is selected from Pseudomonas exotoxin A (PE), where the receptor binding domain is domain Ia of PE (at least col. 93 claim 7), and the transcytosis domain is selected from transcytosis domains besides PE, including botulinum toxin, diptheria toxin, pertussis toxin, cholera toxin, heat labile E. coli enterotoxin, Shiga toxin, and shiga-like toxin (at least col. 93 claim 9). Mrsny discloses that Pseudomonas exotoxin A or PE is a protein composed of three prominent globular domains (I, II, III) and one small subdomain (Ib) that connects domains II and III; domain Ia is believed to mediate cell binding and spans amino acids 1-252; domain II of PE is believed to mediate transcytosis and spans amino acids 253-364; domain Ib has no known function; domain III mediates cytotoxicity of PE (see also col. 5 line 58 to col. 6 line 32, col. 12 lines 12-39, col. 15 lines 55-66). It is disclosed that the composition comprising said delivery construct further comprises a pharmaceutically acceptable diluent excipient, vehicle or carrier, wherein the composition is formulated for nasal or oral administration (at least col. 96 claims 29-30) and/or administration to mucosal membranes including the lungs (at least col. 33 lines 30-35). Mrsny discloses macromolecules for delivery include among others cytokines (at least col. 17 lines 41-43, col. 18 lines 21-23, col. 20 lines 18-27).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed pharmaceutical composition comprising a delivery construct comprising a domain consisting of domain I of a PE (Pseudomonas endotoxin) and a cytokine coupled to the PE domain I, where the delivery construct is configured to deliver the cytokine via transcytosis, and where the pharmaceutical composition is formulated for intra-nasal administration (instant claims 280, 282). The motivation to do so is given by the prior art. In this instance, Mrsny discloses a delivery construct comprising individual or specific domains for delivery of macromolecules by transcytosis, including domain Ia of PE, and coupled to macromolecules for delivery. Therefore, the recited “carrier” can be deemed to be a domain consisting of the recited PE domain I. Therefore, one of ordinary skill would have reasonable motivation to arrive at the claimed delivery construct comprising a domain (or carrier) consisting of domain I of a PE and a cytokine coupled to the domain(s) in the delivery construct because the claimed delivery construct was already disclosed by the prior art. One of ordinary skill would have a reasonable expectation of success because the structure and domains for a delivery construct to deliver macromolecules, including cytokines, by transcytosis were known.
It would have been further obvious to one of ordinary skill that the domain (or carrier) consisting of domain I of a PE and a cytokine coupled to the domain in the delivery construct as suggested in Mrsny above does not comprise a domain Ib, a domain II, and a domain III of PE because as noted above in the Mrsny teachings, Mrsny discloses the delivery construct comprises a domain Ia of PE, where the delivery construct comprises a transcytosis domain that is not from PE and therefore lacks all portions of a domain II of PE, does not comprise domain Ib of PE, and does not comprise domain III of PE.
Regarding instant claim 281, Mrsny discloses that an amino-terminal methionine assists in expression of the construct (at least col. 36 lines 60-61).
Regarding instant claim 283, Mrsny discloses cytokines, including IL-1, IL-10 (at least col. 20 lines 18-22).
Regarding instant claim 284, Mrsny discloses the cytokine is IL-10 (at least col. 20 line 22). It is disclosed in the instant specification that SEQ ID NO: 217 is the amino acid sequence of IL-10.
Regarding instant claim 285, Mrsny discloses the delivery construction compositions are vaccine compositions (at least col. 39 lines 61-65).
Regarding instant claim 286-287, Mrsny discloses the macromolecule for delivery can be a nucleic acid (at least col. 17 lines 30-32), where nucleic acid includes DNA and RNA (at least col. 6 lines 33-54).
Regarding instant claim 288, Mrsny discloses the macromolecule for delivery can be a polypeptide (at least col. 17 lines 30-32).
Regarding instant claim 289-290, Mrsny discloses macromolecules for delivery include among others antibodies and therapeutic antibodies (at least col. 18 lines 6-9, col. 20 line 60).
Regarding instant claim 291-292, it is disclosed in the instant specification that instant SEQ ID NO: 137 is domain I of PE, amino acids 1-252 (specification paragraph 0283). Mrsny discloses domain Ia of PE spans amino acids 1-252 (col. 6 line 2). Therefore, Mrsny can reasonably be deemed to disclose the PE domain I in the delivery construct has at least about 80% sequence identity to instant SEQ ID NO: 137.
Regarding instant claim 293-294, Mrsny discloses the macromolecule (i.e. cytokines, antibodies) to be delivered is connected to the delivery construct by a linker (at least col. 22 lines 20-40, col. 91 claims 1, 7). Therefore, it would be obvious that the macromolecule delivered to the subject is covalently coupled to the delivery construct domain(s).
Regarding instant claim 295, as noted above, Mrsny discloses compositions comprising the delivery construct (at least col. 91 claim 1, col. 94 claim 28). It is disclosed that the composition comprising said delivery construct further comprises a pharmaceutically acceptable diluent excipient, vehicle or carrier, wherein the composition is formulated for nasal or oral administration (at least col. 96 claims 29-30). Mrsny discloses macromolecules for delivery include among others cytokines and antibodies (at least col. 18 lines 6-9, lines 21-23, col. 20 lines 1-27, line 60). Therefore, it would have been obvious to incorporate the delivery construct comprising a domain consisting of a PE domain I and a cytokine or antibody coupled to the PE domain I of Mrsny noted above into a composition comprising a pharmaceutically acceptable excipient, where the composition is formulated for intra-nasal administration.
Regarding instant claims 296, 298, Mrsny discloses macromolecules for delivery include among others cytokines and antibodies (at least col. 18 lines 6-9, lines 21-23, col. 20 lines 1-27, line 60). Mrsny also discloses compositions comprising said delivery construct and the macromolecule further comprises a pharmaceutically acceptable diluent excipient, vehicle or carrier, wherein the composition is formulated for nasal or oral administration (at least col. 96 claims 29-30). Therefore, it would have been obvious to deliver a cytokine or antibody to a subject by administering to the subject by intra-nasal administration, a composition comprising the delivery construct comprising a domain (carrier) consisting of domain I of a PE and an antibody or cytokine coupled to the domain(s) in the delivery construct.
Regarding instant claim 297, it is disclosed in the instant specification that instant SEQ ID NO: 137 is domain I of PE, amino acids 1-252 (specification paragraph 0283). Mrsny discloses domain Ia of PE spans amino acids 1-252 (col. 6 line 2). Therefore, Mrsny can reasonably be deemed to disclose the PE domain I in the delivery construct has at least about 80% sequence identity to instant SEQ ID NO: 137.
Regarding instant claim 299, Mrsny discloses the macromolecule for delivery can be a nucleic acid (at least col. 17 lines 30-32), where nucleic acid includes DNA and RNA (at least col. 6 lines 33-54).
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 280-299 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. 11426466 (‘466) in view of Mrsny (supra). Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant claims and the ‘466 patent claims are drawn to a delivery construct comprising PE domain I and a heterologous cargo (or macromolecules), compositions comprising said delivery construct, and methods for delivering the heterologous cargo to a subject comprising administering said delivery construct to the subject. The ‘466 patent claims differ from the instant claims by not explicitly reciting that the heterologous cargo is a cytokine. However, it is disclosed in the specification of the ‘466 patent that a heterologous cargo includes among others, cytokines, antibodies, diabodies, TNFα antibody, adalimumab (at least col. 107-116). Alternatively, in view of the teachings of Mrsny noted above, it would have been obvious to incorporate a cytokine, cytokine comprising IL-10, an antibody, antibody comprising a diabody, a TNFα antibody, adalimumab, for the heterologous cargo recited in the ‘466 patent claims. One of ordinary skill would have a reasonable expectation of success because the heterologous cargo recited in the ‘466 patent claims include cytokines, antibodies, etc.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Marsha Tsay whose telephone number is (571)272-2938. The examiner can normally be reached on M-F.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath N. Rao can be reached on 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Marsha Tsay/Primary Examiner, Art Unit 1656
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