DETAILED ACTION
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 .
Election/Restrictions
Applicant’s election without traverse of the species of Neu2 and SEQ ID NO: 48 in the reply filed on 09/05/2025 is acknowledged. All of the claims read upon the elected species. Claims 1-3, 5-14, 18, 21, 22, 24-29, 38, 39, 46-50 and 55 are under examination.
Effective Filing Date
Applicant’s claim for the domestic benefit of prior-filed applications under 35 U.S.C. 119(e) and 365(c) is acknowledged. No foreign priority claims are made. Under the AIA , the effective filing date of a claimed invention is the earlier of:
The actual filing date of the application;
OR
The filing date to which the application is entitled to a right of foreign priority or domestic benefit as to such claimed invention.
Note that with regard to claiming domestic benefit of prior-filed applications, MPEP 211.05 sets forth the disclosure requirements:
To be entitled to the benefit of the filing date of an earlier-filed application, the later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or earlier-filed nonprovisional application or provisional application for which benefit is claimed); the disclosure of the invention in the prior application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, except for the best mode requirement. See Transco Prods., Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994). Accordingly, the disclosure of the prior-filed application must provide adequate support and enablement for the claimed subject matter of the later-filed application in compliance with the requirements of 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, except for the best mode requirement.
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Based on the information given by Applicant and an inspection of the prior applications, the examiner has concluded that the subject matter defined in instant claims 1, 5, 7, 9, 10, 12, 13 and 14 is supported by the disclosures of PCT/US2020/040828 and the provisional application serial no. 62/870,403, therefore the effective filing date of these claims is 07/03/2019. The subject matter defined in instant claims 21, 22, 24-29, 38, 39, 46-50 and 55 is supported by the disclosures of PCT/US2020/040828 and the provisional application serial no. 62/957,011, therefore the effective filing date of these claims is 01/03/2020. Neither the ‘403 nor the ‘011 provisional provides support for claims 2, 3, 6, 8, 11 and 18 because those documents do not disclose any substitutions at position 242 corresponding to wild-type Neu2; the specific substitutions recited in claim 6(a) or (b); the Q270S or Q270T in claim 6(c) or all of the sequences recited in claim 18. Thus, the effective filing date of claims 2, 3, 6, 8, 11 and 18 is 07/03/2020. In summary:
Claims 1, 5, 7, 9, 10, 12, 13 and 14 have an effective filing date of 07/03/2019;
Claims 21, 22, 24-29, 38, 39, 46-50 and 55 have an effective filing date of 01/03/2020; and
Claims 2, 3, 6, 8, 11 and 18 have an effective filing date of 07/03/2020.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1-3, 5-12, 18, 21, 22, 24-29, 38, 39, 46-50 and 55 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites a recombinant mutant human sialidase enzyme, wherein the sialidase comprises a substitution of a proline residue at a position corresponding to position 62 of wild-type human Neu2 (P62); and/or a substitution of an alanine residue at a position corresponding to position 93 of wild-type human Neu2 (A93). The instant specification defines sialidase at paragraph [0063]:
As used herein, the term “sialidase” refers to any enzyme, or a functional fragment thereof, that cleaves a terminal sialic acid residue from a substrate, for example, a glycoprotein or a glycolipid. The term sialidase includes variants having one or more amino acid substitutions, deletions, or insertions relative to a wild-type sialidase sequence, and/or fusion proteins or conjugates including a sialidase. Sialidases are also called neuraminidases, and, unless indicated otherwise, the two terms are used interchangeably herein.
The plain meaning of the term “corresponding to” encompasses “similar to” or “analogous to”. Given that the claim recites the term “sialidase” in the first line, but then refers to substitutions at positions in the Neu2 protein, it is not clear whether the claim encompasses substitutions only in the Neu2 protein, or whether the substitutions can occur at positions of other sialidase enzymes that are analogous to the recited positions. Magesh et al. (Journal of Molecular Graphics and Modelling 25 (2006) 196-207) provide the homology modeling of three additional sialidase enzymes, Neu1, Neu3 and Neu4 based upon Neu2. For example, from the sequence alignment in Figure 1 (p. 198), Magesh et al. teach that position 115 of Neu1, position 64 of Neu3 and position 62 of Neu4 “correspond to” position 62 of wild-type human Neu 2. Skilled artisans would not know whether they were infringing upon the claim because claim 1 may reasonably be interpreted as being limited to mutated human Neu2, or alternatively, encompassing a mutation at the positions on other sialidase enzymes that are homologous to the recited positions on human Neu2. For the purpose of applying art, the claims are searched with respect to the elected species of Neu2. Claims 2, 3, 5-12, 18, 21, 22, 24-29, 38, 39, 46-50 and 55 are hereby included in this rejection for depending upon an indefinite claim without resolving the indefiniteness.
Claim 39 recites the third polypeptide comprises the sialidase and the immunoglobulin Fc domain in an N- to C-terminal orientation, however, does not make clear which component is N-terminal and which component is C-terminal. Skilled artisans would not know whether they were infringing upon the claim because claim 39 may be reasonably interpreted as comprising an antibody conjugate in which the sialidase is N-terminal of the Fc domain because the claim recites sialidase prior to the Fc domain. On the other hand, the claim could be reasonably interpreted as encompassing an antibody conjugate in which the sialidase is C-terminal to the Fc domain because the clause does not recite “the sialidase and the immunoglobulin Fc domain in an N- to C-terminal orientation, respectively”. The claims must particularly point out and distinctly define the metes and bounds of the subject matter that will be protected by the patent grant (see MPEP 2171).
Notice for all US Patent Applications filed on or after March 16, 2013: 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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 2, 6, 8 and 18 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Alkhateeb et al. (WO2020/142727), which for the purpose of this rejection was effectively filed 01/03/2020. (Note that while Alkhateeb et al. claim priority to 62/787,935, filed 01/03/2019, the priority document does not disclose P62 or A93 mutations as required by the instant claims). Claims 2, 6, 8 and 18 have the effective filing date of 07/03/2020, which is later than that of the claims upon which they depend, and thus, the claims are treated as independent for the purpose of applying prior art. Note that the effective filing date of a claimed invention is determined on a claim-by-claim basis and not on an application-by-application basis. That is, the principle that different claims in the same application may be entitled to different effective filing dates vis-à-vis the prior art remains unchanged by the AIA (see MPEP 2152.01).
Alkhateeb et al. teach a recombinant human sialidase comprising a substitution of a proline residue at a position corresponding to position 62 of wild-type human Neu2 (P62), for instance, P62N, P62D, P62H, P62E, P62G, P62S, or P62T; a substitution of an alanine residue at a position corresponding to position 93 of wild-type human Neu2 (A93), for instance, A93E or A93K; a glutamine residue at a position corresponding to position 126 of wild-type human Neu2 (Q126), for instance Q126L; and a glutamine residue at a position corresponding to position 270 of wild-type human Neu2 (Q270), for instance, Q270A, Q270H, Q270F or Q270P (see paragraph [0075]). Further, Alkhateeb et al. teach SEQ ID NO: 83, which shares 100% sequence identity to the elected instant SEQ ID NO: 48:
Qy 1 DASLPYLQKESVFQSGAHAYRIPALLYLPGQQSLLAFAEQRASKKDEHAELIVLRRGDYD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DASLPYLQKESVFQSGAHAYRIPALLYLPGQQSLLAFAEQRASKKDEHAELIVLRRGDYD 60
Qy 61 AGTHQVQWQAQEVVAQARLDGHRSMNPCPLYDEQTGTLFLFFIAIPGQVTEQQQLQTRAN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AGTHQVQWQAQEVVAQARLDGHRSMNPCPLYDEQTGTLFLFFIAIPGQVTEQQQLQTRAN 120
Qy 121 VTRLCQVTSTDHGRTWSSPRDLTDAAIGPAYREWSTFAVGPGHCLQLHDRARSLVVPAYA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VTRLCQVTSTDHGRTWSSPRDLTDAAIGPAYREWSTFAVGPGHCLQLHDRARSLVVPAYA 180
Qy 181 YRKLHPKQRPIPSAFCFLSHDHGRTWARGHFVAQDTLECQVAEVETGEQRVVTLNARSHL 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 YRKLHPKQRPIPSAFCFLSHDHGRTWARGHFVAQDTLECQVAEVETGEQRVVTLNARSHL 240
Qy 241 RARVQAQSTNDGLDFQESQLVKKLVEPPPQGCQGSVISFPSPRSGPGSPAQWLLYTHPTH 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 RARVQAQSTNDGLDFQESQLVKKLVEPPPQGCQGSVISFPSPRSGPGSPAQWLLYTHPTH 300
Qy 301 SWQRADLGAYLNPRPPAPEAWSEPVLLAKGSAAYSDLQSMGTGPDGSPLFGCLYEANDYE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 SWQRADLGAYLNPRPPAPEAWSEPVLLAKGSAAYSDLQSMGTGPDGSPLFGCLYEANDYE 360
Qy 361 EIVFLMFTLKQAFPAEYLPQ 380
||||||||||||||||||||
Db 361 EIVFLMFTLKQAFPAEYLPQ 380
Thus, Alkhateeb and colleagues teach the limitations of claims 2, 6, 8 and 18.
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.
17/624,118
Claims 1-3, 5-14, 18, 21, 22, 24-29, 38, 39, 46-50 and 55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 8, 12-14, 16, 21, 25, 27, 29-33, 44, 45, 47, 55-57, 59, 61 and 63-67 of copending Application No. 17/624,118 (reference application). The claims of the reference application are drawn to an antibody conjugate (i.e., a fusion) comprising a recombinant mutant human sialidase enzyme and an anti-CD20 immunoglobulin antigen-binding domain. The claims of the reference application encompass the same substitutions to the sialidase as recited in the instant claims, namely a substitution to:
A proline residue at a position corresponding to position 62 of wild-type human Neu2 (P62), for instance, P62N, P62D, P62H, P62E, P62G, P62S, or P62T;
An alanine residue at a position corresponding to position 93 of wild-type human Neu2 (A93), for instance, A93E or A93K;
A glutamine residue at a position corresponding to position 126 of wild-type human Neu2 (Q126), for instance, Q126L, Q126E, Q126F, Q126H, Q126I, or Q126Y;
An alanine residue at a position corresponding to position 242 of wild-type human Neu2 (A242), for instance, A242C, A242F, A242G, A242H, A242I, A242K, A242L, A242M, A242N, A242Q, A242R), A242S, A242V), A242W, A242Y; or
A glutamine residue at a position corresponding to position 270 of wild-type human Neu2 (Q270), for instance, Q270A, Q270H, Q270F, Q270P, Q270S, or Q270T.
In addition, the claims of the reference application encompass the same additional mutations to sialidase as those recited in the instant claims:
A substitution (M1A or M1D) or deletion (ΔM1) of a methionine residue at a position corresponding to position 1 of wild-type human Neu2;
A substitution of a valine residue at a position corresponding to position 6 of wild- type human Neu2 (V6), e.g., V6Y
A substitution of an isoleucine residue at a position corresponding to position 187 of wild-type human Neu2 (I187), e.g., I187K; or
A substitution of a cysteine residue at a position corresponding to position 332 of wild-type human Neu2 (C332), e.g., C332A.
Claim 14 of the reference application encompasses the same mutations to the sialidase as recited in instant claims 11 and 12.
The claims of the reference application also recite that the sialidase is selected from Neu1, Neu2, Neu3, and Neu4 and may comprise the sequence set forth in SEQ ID NO: 48, which shares 100% sequence identity with instant SEQ ID NO: 48:
RESULT 1
US-17-624-121-48
Query Match 100.0%; Score 2029; DB 1; Length 380;
Best Local Similarity 100.0%;
Matches 380; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DASLPYLQKESVFQSGAHAYRIPALLYLPGQQSLLAFAEQRASKKDEHAELIVLRRGDYD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DASLPYLQKESVFQSGAHAYRIPALLYLPGQQSLLAFAEQRASKKDEHAELIVLRRGDYD 60
Qy 61 AGTHQVQWQAQEVVAQARLDGHRSMNPCPLYDEQTGTLFLFFIAIPGQVTEQQQLQTRAN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AGTHQVQWQAQEVVAQARLDGHRSMNPCPLYDEQTGTLFLFFIAIPGQVTEQQQLQTRAN 120
Qy 121 VTRLCQVTSTDHGRTWSSPRDLTDAAIGPAYREWSTFAVGPGHCLQLHDRARSLVVPAYA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VTRLCQVTSTDHGRTWSSPRDLTDAAIGPAYREWSTFAVGPGHCLQLHDRARSLVVPAYA 180
Qy 181 YRKLHPKQRPIPSAFCFLSHDHGRTWARGHFVAQDTLECQVAEVETGEQRVVTLNARSHL 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 YRKLHPKQRPIPSAFCFLSHDHGRTWARGHFVAQDTLECQVAEVETGEQRVVTLNARSHL 240
Qy 241 RARVQAQSTNDGLDFQESQLVKKLVEPPPQGCQGSVISFPSPRSGPGSPAQWLLYTHPTH 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 RARVQAQSTNDGLDFQESQLVKKLVEPPPQGCQGSVISFPSPRSGPGSPAQWLLYTHPTH 300
Qy 301 SWQRADLGAYLNPRPPAPEAWSEPVLLAKGSAAYSDLQSMGTGPDGSPLFGCLYEANDYE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 SWQRADLGAYLNPRPPAPEAWSEPVLLAKGSAAYSDLQSMGTGPDGSPLFGCLYEANDYE 360
Qy 361 EIVFLMFTLKQAFPAEYLPQ 380
||||||||||||||||||||
Db 361 EIVFLMFTLKQAFPAEYLPQ 380
The claims of the reference application recite the antibody conjugate further comprises an immunoglobulin Fc derived from a human IgG1, IgG2, IgG3, or IgG4 Fc domain and the antibody is selected from ofatumumab, rituximab, among others, wherein the components are joined by a peptide bond or an amino acid linker, wherein the third polypeptide comprises the sialidase and the immunoglobulin Fc domain in an N- to C-terminal orientation. Finally, the claims of the reference application encompass an isolated nucleic acid encoding the fusion protein antibody conjugate, an expression vector comprising the nucleic acid, a host cell comprising the expression vector, a pharmaceutical composition comprising the antibody conjugate and a method of treating cancer therewith.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the reference application, which specifically recite CD20, are more specific with respect to the immunoglobulin antigen-binding domain and the species anticipates the genus.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
17/624,116
Claims 1-3, 5-14, 18, 21, 22, 24-29, 38, 39, 46-50 and 55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 8, 12-14, 16, 21, 25, 27, 29-33, 35, 44-46 and 60-64 of copending Application No. 17/624,116 (reference application). The claims of the reference application are drawn to a fusion protein comprising a recombinant mutant human sialidase enzyme and an anti-PD-L1 immunoglobulin antigen-binding domain (i.e., an antibody conjugate). The claims of the reference application encompass the same substitutions to the sialidase as recited in the instant claims, namely a substitution to:
A proline residue at a position corresponding to position 62 of wild-type human Neu2 (P62), for instance, P62N, P62D, P62H, P62E, P62G, P62S, or P62T;
An alanine residue at a position corresponding to position 93 of wild-type human Neu2 (A93), for instance, A93E or A93K;
A glutamine residue at a position corresponding to position 126 of wild-type human Neu2 (Q126), for instance, Q126L, Q126E, Q126F, Q126H, Q126I, or Q126Y;
An alanine residue at a position corresponding to position 242 of wild-type human Neu2 (A242), for instance, A242C, A242F, A242G, A242H, A242I, A242K, A242L, A242M, A242N, A242Q, A242R, A242S, A242V, A242W, A242Y; or
A glutamine residue at a position corresponding to position 270 of wild-type human Neu2 (Q270), for instance, Q270A, Q270H, Q270F, Q270P, Q270S, or Q270T.
In addition, the claims of the reference application encompass the same additional mutations to sialidase as those recited in the instant claims:
A substitution (M1A or M1D) or deletion (ΔM1) of a methionine residue at a position corresponding to position 1 of wild-type human Neu2;
A substitution of a valine residue at a position corresponding to position 6 of wild- type human Neu2 (V6), e.g., V6Y
A substitution of an isoleucine residue at a position corresponding to position 187 of wild-type human Neu2 (I187), e.g., I187K; or
A substitution of a cysteine residue at a position corresponding to position 332 of wild-type human Neu2 (C332), e.g., C332A.
Claim 14 of the reference application encompasses the same combination of mutations to the sialidase as recited in instant claims 11 and 12.
The claims of the reference application also recite that the sialidase is selected from Neu1, Neu2, Neu3, and Neu4 and may comprise the sequence set forth in SEQ ID NO: 48, which shares 100% sequence identity with instant SEQ ID NO: 48:
RESULT 1
US-17-624-121-48
Query Match 100.0%; Score 2029; DB 1; Length 380;
Best Local Similarity 100.0%;
Matches 380; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DASLPYLQKESVFQSGAHAYRIPALLYLPGQQSLLAFAEQRASKKDEHAELIVLRRGDYD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DASLPYLQKESVFQSGAHAYRIPALLYLPGQQSLLAFAEQRASKKDEHAELIVLRRGDYD 60
Qy 61 AGTHQVQWQAQEVVAQARLDGHRSMNPCPLYDEQTGTLFLFFIAIPGQVTEQQQLQTRAN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AGTHQVQWQAQEVVAQARLDGHRSMNPCPLYDEQTGTLFLFFIAIPGQVTEQQQLQTRAN 120
Qy 121 VTRLCQVTSTDHGRTWSSPRDLTDAAIGPAYREWSTFAVGPGHCLQLHDRARSLVVPAYA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VTRLCQVTSTDHGRTWSSPRDLTDAAIGPAYREWSTFAVGPGHCLQLHDRARSLVVPAYA 180
Qy 181 YRKLHPKQRPIPSAFCFLSHDHGRTWARGHFVAQDTLECQVAEVETGEQRVVTLNARSHL 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 YRKLHPKQRPIPSAFCFLSHDHGRTWARGHFVAQDTLECQVAEVETGEQRVVTLNARSHL 240
Qy 241 RARVQAQSTNDGLDFQESQLVKKLVEPPPQGCQGSVISFPSPRSGPGSPAQWLLYTHPTH 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 RARVQAQSTNDGLDFQESQLVKKLVEPPPQGCQGSVISFPSPRSGPGSPAQWLLYTHPTH 300
Qy 301 SWQRADLGAYLNPRPPAPEAWSEPVLLAKGSAAYSDLQSMGTGPDGSPLFGCLYEANDYE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 SWQRADLGAYLNPRPPAPEAWSEPVLLAKGSAAYSDLQSMGTGPDGSPLFGCLYEANDYE 360
Qy 361 EIVFLMFTLKQAFPAEYLPQ 380
||||||||||||||||||||
Db 361 EIVFLMFTLKQAFPAEYLPQ 380
The claims of the reference application recite the antibody conjugate further comprises an immunoglobulin Fc derived from a human IgG1, IgG2, IgG3, or IgG4 Fc domain and the antibody is selected from avelumab, among others, wherein the components are joined by a peptide bond or an amino acid linker, wherein the third polypeptide comprises the sialidase and the immunoglobulin Fc domain in an N- to C-terminal orientation. Finally, the claims of the reference application encompass an isolated nucleic acid encoding the fusion protein antibody conjugate, an expression vector comprising the nucleic acid, a host cell comprising the expression vector, a pharmaceutical composition comprising the antibody conjugate and a method of treating cancer therewith.
Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the reference application recite more alternative mutations in addition to those recited in the instant claims. Nevertheless, when the species are clearly named, as they are in the claims of the reference application, this is anticipatory no matter how many other species are additionally named. Further, the claims of the reference application are more specific with respect to the immunoglobulin antigen-binding domain; however, the species anticipates the genus.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
18/003,234
Claims 1-3, 5-14, 18, 21, 22, 24-29, 38, 39, 46-50 and 55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 7, 11, 15-20, 24, 27, 28, 30, 32-36, 45, 46 and 53-57 of copending Application No. 18/003,234 (reference application). The claims of the reference application are drawn to a recombinant mutant human sialidase enzyme and an immunoglobulin Fc domain. The claims of the reference application encompass the same substitutions to the sialidase as recited in the instant claims, namely a substitution to:
A proline residue at a position corresponding to position 62 of wild-type human Neu2 (P62), for instance, P62N, P62D, P62H, P62E, P62G, P62S, or P62T;
An alanine residue at a position corresponding to position 93 of wild-type human Neu2 (A93), for instance, A93E or A93K;
A glutamine residue at a position corresponding to position 126 of wild-type human Neu2 (Q126), for instance, Q126L, Q126E, Q126F, Q126H, Q126I, or Q126Y;
An alanine residue at a position corresponding to position 242 of wild-type human Neu2 (A242), for instance, A242C, A242F, A242G, A242H, A242I, A242K, A242L, A242M, A242N, A242Q, A242R, A242S, A242V, A242W, A242Y; or
A glutamine residue at a position corresponding to position 270 of wild-type human Neu2 (Q270), for instance, Q270A, Q270H, Q270F, Q270P, Q270S, or Q270T.
In addition, the claims of the reference application encompass the same additional mutations to sialidase as those recited in the instant claims:
A substitution (M1A or M1D) or deletion (ΔM1) of a methionine residue at a position corresponding to position 1 of wild-type human Neu2;
A substitution of a valine residue at a position corresponding to position 6 of wild- type human Neu2 (V6), e.g., V6Y
A substitution of an isoleucine residue at a position corresponding to position 187 of wild-type human Neu2 (I187), e.g., I187K; or
A substitution of a cysteine residue at a position corresponding to position 332 of wild-type human Neu2 (C332), e.g., C332A.
Claim 17 of the reference application encompass the same mutations to the sialidase as recited in instant claims 11 and 12.
The claims of the reference application also recite that the sialidase is selected from Neu1, Neu2, Neu3, and Neu4 and may comprise the sequence set forth in SEQ ID NO: 48, which shares 100% sequence identity with instant SEQ ID NO: 48:
RESULT 1
US-17-624-121-48
Query Match 100.0%; Score 2029; DB 1; Length 380;
Best Local Similarity 100.0%;
Matches 380; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DASLPYLQKESVFQSGAHAYRIPALLYLPGQQSLLAFAEQRASKKDEHAELIVLRRGDYD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DASLPYLQKESVFQSGAHAYRIPALLYLPGQQSLLAFAEQRASKKDEHAELIVLRRGDYD 60
Qy 61 AGTHQVQWQAQEVVAQARLDGHRSMNPCPLYDEQTGTLFLFFIAIPGQVTEQQQLQTRAN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AGTHQVQWQAQEVVAQARLDGHRSMNPCPLYDEQTGTLFLFFIAIPGQVTEQQQLQTRAN 120
Qy 121 VTRLCQVTSTDHGRTWSSPRDLTDAAIGPAYREWSTFAVGPGHCLQLHDRARSLVVPAYA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VTRLCQVTSTDHGRTWSSPRDLTDAAIGPAYREWSTFAVGPGHCLQLHDRARSLVVPAYA 180
Qy 181 YRKLHPKQRPIPSAFCFLSHDHGRTWARGHFVAQDTLECQVAEVETGEQRVVTLNARSHL 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 YRKLHPKQRPIPSAFCFLSHDHGRTWARGHFVAQDTLECQVAEVETGEQRVVTLNARSHL 240
Qy 241 RARVQAQSTNDGLDFQESQLVKKLVEPPPQGCQGSVISFPSPRSGPGSPAQWLLYTHPTH 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 RARVQAQSTNDGLDFQESQLVKKLVEPPPQGCQGSVISFPSPRSGPGSPAQWLLYTHPTH 300
Qy 301 SWQRADLGAYLNPRPPAPEAWSEPVLLAKGSAAYSDLQSMGTGPDGSPLFGCLYEANDYE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 SWQRADLGAYLNPRPPAPEAWSEPVLLAKGSAAYSDLQSMGTGPDGSPLFGCLYEANDYE 360
Qy 361 EIVFLMFTLKQAFPAEYLPQ 380
||||||||||||||||||||
Db 361 EIVFLMFTLKQAFPAEYLPQ 380
The claims of the reference application recite the antibody conjugate further comprises an immunoglobulin Fc derived from a human IgG1, IgG2, IgG3, or IgG4 Fc domain and the antibody is selected from ofatumumab, avelumab, rituximab, among others, wherein the components are joined by a peptide bond or an amino acid linker, wherein the third polypeptide comprises the sialidase and the immunoglobulin Fc domain in an N- to C-terminal orientation. Finally, the claims of the reference application encompass an isolated nucleic acid encoding the fusion protein antibody conjugate, an expression vector comprising the nucleic acid, a host cell comprising the expression vector, a pharmaceutical composition comprising the antibody conjugate and a method of treating cancer therewith.
Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the reference application recite more alternative mutations in addition to those recited in the instant claims. Nevertheless, when the species are clearly named, as they are in the claims of the reference application, this is anticipatory no matter how many other species are additionally named. See MPEP 2131.02(II)(A), citing Ex parte A, 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
18/260,383
Claims 1-3, 5-14, 18, 21, 22, 24-29, 38, 39, 46-50 and 55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5, 9, 11, 15, 17, 19, 21-23, 25, 26, 35-37, 48-52, 60, 65, 66 and 68 of copending Application No. 18/260,383 (reference application) in view of Dimasi (US20120213705). The claims of the reference application are drawn to an antibody conjugate (i.e., a fusion) comprising a recombinant mutant human sialidase enzyme and an anti-HER2 immunoglobulin antigen-binding domain. The claims of the reference application encompass the same substitutions to the sialidase as recited in the instant claims, namely:
A substitution (M1A or M1D) or deletion (ΔM1) of a methionine residue at a position corresponding to position 1 of wild-type human Neu2;
A substitution of a valine residue at a position corresponding to position 6 of wild- type human Neu2 (V6), e.g., V6Y
A proline residue at a position corresponding to position 62 of wild-type human Neu2 (P62), for instance, P62N, P62D, P62H, P62E, P62G, P62S, or P62T;
An alanine residue at a position corresponding to position 93 of wild-type human Neu2 (A93), for instance, A93E or A93K;
A glutamine residue at a position corresponding to position 126 of wild-type human Neu2 (Q126), for instance, Q126L, Q126E, Q126F, Q126H, Q126I, or Q126Y;
An alanine residue at a position corresponding to position 242 of wild-type human Neu2 (A242), for instance, A242C, A242F, A242G, A242H, A242I, A242K, A242L, A242M, A242N, A242Q, A242R, A242S, A242V, A242W, A242Y; or
A glutamine residue at a position corresponding to position 270 of wild-type human Neu2 (Q270), for instance, Q270A, Q270H, Q270F, Q270P, Q270S, or Q270T; or
A substitution of a cysteine residue at a position corresponding to position 332 of wild-type human Neu2 (C332), e.g., C332A.
The claims of the reference application also recite that the sialidase may comprise the sequence set forth in SEQ ID NO: 198, which shares >98% sequence identity with instant SEQ ID NO: 48:
RESULT 1
US-17-624-121-48
Query Match 98.6%; Score 2006; DB 1; Length 380;
Best Local Similarity 98.9%;
Matches 376; Conservative 0; Mismatches 4; Indels 0; Gaps 0;
Qy 1 DASLPYLQKESVFQSGAHAYRIPALLYLPGQQSLLAFAEQRRSKKDEHAELIVLRRGDYD 60
||||||||||||||||||||||||||||||||||||||||| ||||||||||||||||||
Db 1 DASLPYLQKESVFQSGAHAYRIPALLYLPGQQSLLAFAEQRASKKDEHAELIVLRRGDYD 60
Qy 61 AGTHQVQWQAQEVVAQARLDGHRSMNPCPLYDEQTGTLFLFFIAIPGQVTEQQQLQTRAN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AGTHQVQWQAQEVVAQARLDGHRSMNPCPLYDEQTGTLFLFFIAIPGQVTEQQQLQTRAN 120
Qy 121 VTRLCYVTSTDHGRTWSSPRDLTDAAIGPAYREWSTFAVGPGHCLQLHDRARSLVVPAYA 180
||||| ||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VTRLCQVTSTDHGRTWSSPRDLTDAAIGPAYREWSTFAVGPGHCLQLHDRARSLVVPAYA 180
Qy 181 YRKLHPKQRPIPSAFCFLSHDHGRTWARGHFVAQDTLECQVAEVETGEQRVVTLNARSHL 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 YRKLHPKQRPIPSAFCFLSHDHGRTWARGHFVAQDTLECQVAEVETGEQRVVTLNARSHL 240
Qy 241 RFRVQAQSTNDGLDFQESQLVKKLVEPPPTGCQGSVISFPSPRSGPGSPAQWLLYTHPTH 300
| ||||||||||||||||||||||||||| ||||||||||||||||||||||||||||||
Db 241 RARVQAQSTNDGLDFQESQLVKKLVEPPPQGCQGSVISFPSPRSGPGSPAQWLLYTHPTH 300
Qy 301 SWQRADLGAYLNPRPPAPEAWSEPVLLAKGSAAYSDLQSMGTGPDGSPLFGCLYEANDYE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 SWQRADLGAYLNPRPPAPEAWSEPVLLAKGSAAYSDLQSMGTGPDGSPLFGCLYEANDYE 360
Qy 361 EIVFLMFTLKQAFPAEYLPQ 380
||||||||||||||||||||
Db 361 EIVFLMFTLKQAFPAEYLPQ 380
The sequence set forth in SEQ ID NO: 198 of the reference application encompasses the substitutions set forth in instant claim 12 (see underlined residues in the alignment).
The claims of the reference application recite the antibody conjugate further comprises an immunoglobulin Fc derived from a human IgG1, IgG2, IgG3, or IgG4 Fc domain and the antibody is selected from trastuzumab, among others, wherein the third polypeptide comprises the sialidase and the immunoglobulin Fc domain in an N- to C-terminal orientation. Finally, the claims of the reference application encompass an isolated nucleic acid encoding the fusion protein antibody conjugate, an expression vector comprising the nucleic acid, a host cell comprising the expression vector, a pharmaceutical composition comprising the antibody conjugate and a method of treating cancer therewith.
Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the reference application are more specific with respect to the immunoglobulin antigen-binding domain, however, the species anticipates the genus. Further, the claims of the reference application recite more alternative mutations in addition to those recited in the instant claims. Nevertheless, when the species are clearly named, as they are in the claims of the reference application, this is anticipatory no matter how many other species are additionally named. See MPEP 2131.02(II)(A), citing Ex parte A, 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990). The claims of the reference application encompass all of the substitutions set forth in instant claim 11, although they are found in a single list. Finally, the claims of the reference application recite covalent bonding rather than peptide bonds and linkers, however, such minor differences are not patentably distinguishable. Evidence for this is found in Dimasi, who teach that Fc regions may be conjugated both covalently and through linkers (see paragraph [0164]).
This is a provisional nonstatutory double patenting rejection.
18/260,378
Claims 1-3, 5-14, 18, 21, 22, 24-29, 38, 39, 46-50 and 55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 4-6, 9, 13, 15, 17, 19-21, 23, 24, 33-35 and 44-48 of copending Application No. 18/260,378 (reference application) in view of Dimasi (US20120213705). The claims of the reference application are drawn to an antibody conjugate (i.e., a fusion) comprising a recombinant mutant human sialidase enzyme and an anti-PD-1 immunoglobulin antigen-binding domain. The claims of the reference application encompass the same substitutions to the sialidase as recited in the instant claims, namely:
A substitution (M1A or M1D) or deletion (ΔM1) of a methionine residue at a position corresponding to position 1 of wild-type human Neu2;
A substitution of a valine residue at a position corresponding to position 6 of wild- type human Neu2 (V6), e.g., V6Y
A proline residue at a position corresponding to position 62 of wild-type human Neu2 (P62), for instance, P62N, P62D, P62H, P62E, P62G, P62S, or P62T;
An alanine residue at a position corresponding to position 93 of wild-type human Neu2 (A93), for instance, A93E or A93K;
A glutamine residue at a position corresponding to position 126 of wild-type human Neu2 (Q126), for instance, Q126L, Q126E, Q126F, Q126H, Q126I, or Q126Y;
An alanine residue at a position corresponding to position 242 of wild-type human Neu2 (A242), for instance, A242C, A242F, A242G, A242H, A242I, A242K, A242L, A242M, A242N, A242Q, A242R, A242S, A242V, A242W, A242Y; or
A glutamine residue at a position corresponding to position 270 of wild-type human Neu2 (Q270), for instance, Q270A, Q270H, Q270F, Q270P, Q270S, or Q270T; or
A substitution of a cysteine residue at a position corresponding to position 332 of wild-type human Neu2 (C332), e.g., C332A.
Claim 6 of the reference encompasses substitutions set forth in instant claims 11 and 12.
Claim 13 of the reference application also recites that the sialidase may comprise the sequence set forth in SEQ ID NO: 48, which shares 100% sequence identity with instant SEQ ID NO: 48:
Query Match 100.0%; Score 2029; DB 1; Length 380;
Best Local Similarity 100.0%;
Matches 380; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DASLPYLQKESVFQSGAHAYRIPALLYLPGQQSLLAFAEQRASKKDEHAELIVLRRGDYD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DASLPYLQKESVFQSGAHAYRIPALLYLPGQQSLLAFAEQRASKKDEHAELIVLRRGDYD 60
Qy 61 AGTHQVQWQAQEVVAQARLDGHRSMNPCPLYDEQTGTLFLFFIAIPGQVTEQQQLQTRAN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AGTHQVQWQAQEVVAQARLDGHRSMNPCPLYDEQTGTLFLFFIAIPGQVTEQQQLQTRAN 120
Qy 121 VTRLCQVTSTDHGRTWSSPRDLTDAAIGPAYREWSTFAVGPGHCLQLHDRARSLVVPAYA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VTRLCQVTSTDHGRTWSSPRDLTDAAIGPAYREWSTFAVGPGHCLQLHDRARSLVVPAYA 180
Qy 181 YRKLHPKQRPIPSAFCFLSHDHGRTWARGHFVAQDTLECQVAEVETGEQRVVTLNARSHL 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 YRKLHPKQRPIPSAFCFLSHDHGRTWARGHFVAQDTLECQVAEVETGEQRVVTLNARSHL 240
Qy 241 RARVQAQSTNDGLDFQESQLVKKLVEPPPQGCQGSVISFPSPRSGPGSPAQWLLYTHPTH 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 RARVQAQSTNDGLDFQESQLVKKLVEPPPQGCQGSVISFPSPRSGPGSPAQWLLYTHPTH 300
Qy 301 SWQRADLGAYLNPRPPAPEAWSEPVLLAKGSAAYSDLQSMGTGPDGSPLFGCLYEANDYE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 SWQRADLGAYLNPRPPAPEAWSEPVLLAKGSAAYSDLQSMGTGPDGSPLFGCLYEANDYE 360
Qy 361 EIVFLMFTLKQAFPAEYLPQ 380
||||||||||||||||||||
Db 361 EIVFLMFTLKQAFPAEYLPQ 380
The claims of the reference application recite the antibody conjugate further comprises an immunoglobulin Fc derived from a human IgG1, IgG2, IgG3, or IgG4 Fc domain and the antibody is selected from trastuzumab, among others, wherein the third polypeptide comprises the sialidase and the immunoglobulin Fc domain in an N- to C-terminal orientation. Finally, the claims of the reference application encompass an isolated nucleic acid encoding the fusion protein antibody conjugate, an expression vector comprising the nucleic acid, a host cell comprising the expression vector, a pharmaceutical composition comprising the antibody conjugate and a method of treating cancer therewith.
Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the reference application are more specific with respect to the immunoglobulin antigen-binding domain, however, the species anticipates the genus. Further, the claims of the reference application recite more alternative mutations in addition to those recited in the instant claims. Nevertheless, when the species are clearly named, as they are in the claims of the reference application, this is anticipatory no matter how many other species are additionally named. See MPEP 2131.02(II)(A), citing Ex parte A, 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990). The claims of the reference application encompass all of the substitutions set forth in instant claim 12, although they are not found in a single list. Finally, the claims of the reference application recite covalent bonding rather than peptide bonds and linkers, however, such minor differences are not patentably distinguishable. Evidence for this is found in Dimasi, who teach that Fc regions may be conjugated both covalently and through linkers (see paragraph [0164]).
This is a provisional nonstatutory double patenting rejection.
18/260,364
Claims 1-3, 5-14, 18, 21, 22, 24-29, 38, 39, 46-50 and 55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 10-12, 15-18, 21, 25, 27, 29, 31, 33, 34, 43-45 and 54-58 of copending Application No. 18/260,364 (reference application) in view of Dimasi (US20120213705). The claims of the reference application are drawn to a fusion protein (i.e., an antibody conjugate) comprising a recombinant mutant human sialidase enzyme and an anti-PD-L1 immunoglobulin antigen-binding domain. The claims of the reference application encompass the same substitutions to the sialidase as recited in the instant claims, namely:
A substitution (M1A or M1D) or deletion (ΔM1) of a methionine residue at a position corresponding to position 1 of wild-type human Neu2;
A substitution of a valine residue at a position corresponding to position 6 of wild- type human Neu2 (V6), e.g., V6Y
A proline residue at a position corresponding to position 62 of wild-type human Neu2 (P62), for instance, P62N, P62D, P62H, P62E, P62G, P62S, or P62T;
An alanine residue at a position corresponding to position 93 of wild-type human Neu2 (A93), for instance, A93E or A93K;
A glutamine residue at a position corresponding to position 126 of wild-type human Neu2 (Q126), for instance, Q126L, Q126E, Q126F, Q126H, Q126I, or Q126Y;
An alanine residue at a position corresponding to position 242 of wild-type human Neu2 (A242), for instance, A242C, A242F, A242G, A242H, A242I, A242K, A242L, A242M, A242N, A242Q, A242R, A242S, A242V, A242W, A242Y; or
A glutamine residue at a position corresponding to position 270 of wild-type human Neu2 (Q270), for instance, Q270A, Q270H, Q270F, Q270P, Q270S, or Q270T; or
A substitution of a cysteine residue at a position corresponding to position 332 of wild-type human Neu2 (C332), e.g., C332A.
Claim 18 of the reference application encompasses the substitutions set forth in instant claims 11 and 12.
Claim 25 of the reference application also recites that the sialidase may comprise the sequence set forth in SEQ ID NO: 48, which shares 100% sequence identity with instant SEQ ID NO: 48:
Query Match 100.0%; Score 2029; DB 1; Length 380;
Best Local Similarity 100.0%;
Matches 380; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DASLPYLQKESVFQSGAHAYRIPALLYLPGQQSLLAFAEQRASKKDEHAELIVLRRGDYD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DASLPYLQKESVFQSGAHAYRIPALLYLPGQQSLLAFAEQRASKKDEHAELIVLRRGDYD 60
Qy 61 AGTHQVQWQAQEVVAQARLDGHRSMNPCPLYDEQTGTLFLFFIAIPGQVTEQQQLQTRAN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AGTHQVQWQAQEVVAQARLDGHRSMNPCPLYDEQTGTLFLFFIAIPGQVTEQQQLQTRAN 120
Qy 121 VTRLCQVTSTDHGRTWSSPRDLTDAAIGPAYREWSTFAVGPGHCLQLHDRARSLVVPAYA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VTRLCQVTSTDHGRTWSSPRDLTDAAIGPAYREWSTFAVGPGHCLQLHDRARSLVVPAYA 180
Qy 181 YRKLHPKQRPIPSAFCFLSHDHGRTWARGHFVAQDTLECQVAEVETGEQRVVTLNARSHL 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 YRKLHPKQRPIPSAFCFLSHDHGRTWARGHFVAQDTLECQVAEVETGEQRVVTLNARSHL 240
Qy 241 RARVQAQSTNDGLDFQESQLVKKLVEPPPQGCQGSVISFPSPRSGPGSPAQWLLYTHPTH 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 RARVQAQSTNDGLDFQESQLVKKLVEPPPQGCQGSVISFPSPRSGPGSPAQWLLYTHPTH 300
Qy 301 SWQRADLGAYLNPRPPAPEAWSEPVLLAKGSAAYSDLQSMGTGPDGSPLFGCLYEANDYE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 SWQRADLGAYLNPRPPAPEAWSEPVLLAKGSAAYSDLQSMGTGPDGSPLFGCLYEANDYE 360
Qy 361 EIVFLMFTLKQAFPAEYLPQ 380
||||||||||||||||||||
Db 361 EIVFLMFTLKQAFPAEYLPQ 380
The claims of the reference application recite the antibody conjugate further comprises an immunoglobulin Fc derived from a human IgG1, IgG2, IgG3, or IgG4 Fc domain and the antibody is selected from trastuzumab, among others, wherein the third polypeptide comprises the sialidase and the immunoglobulin Fc domain in an N- to C-terminal orientation. Finally, the claims of the reference application encompass an isolated nucleic acid encoding the fusion protein antibody conjugate, an expression vector comprising the nucleic acid, a host cell comprising the expression vector, a pharmaceutical composition comprising the antibody conjugate and a method of treating cancer therewith.
Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the reference application are more specific with respect to the immunoglobulin antigen-binding domain, however, the species anticipates the genus. Further, the claims of the reference application recite more alternative mutations in addition to those recited in the instant claims. Nevertheless, when the species are clearly named, as they are in the claims of the reference application, this is anticipatory no matter how many other species are additionally named. See MPEP 2131.02(II)(A), citing Ex parte A, 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990). The claims of the reference application encompass all of the substitutions set forth in instant claim 12, although they are not found in a single list. Finally, the claims of the reference application recite covalent bonding rather than peptide bonds and linkers, however, such minor differences are not patentably distinguishable. Evidence for this is found in Dimasi, who teach that Fc regions may be conjugated both covalently and through linkers (see paragraph [0164]).
This is a provisional nonstatutory double patenting rejection.
17/624,123
Claims 1-3, 5-14, 18, 21, 22, 24-29, 38, 39, 46-50 and 55 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 11-18, 20, 24-26, 32, 33, 68, 71, 72, 74 and 79-83 of copending Application No. 17/624,123 (reference application) in view of Woods et al. (WO 2018/006034). The claims of the reference application encompass a pharmaceutical composition comprising a human neu2 sialidase conjugated to, for example, an Fc domain. The sialidase comprises the same mutations as those recited in the instant claims, for example:
A substitution (M1A or M1D) or deletion (ΔM1) of a methionine residue at a position corresponding to position 1 of wild-type human Neu2;
A substitution of a valine residue at a position corresponding to position 6 of wild- type human Neu2 (V6), e.g., V6Y
A substitution of an isoleucine residue at a position corresponding to position 187 of wild-type human Neu2 (I187), e.g., I187K;
A substitution of a cysteine residue at a position corresponding to position 332 of wild-type human Neu2 (C332), e.g., C332A;
A substitution of a proline residue at a position corresponding to position 62 of wild-type human Neu2 (P62);
A substitution of an alanine residue at a position corresponding to position 93 of wild- type human Neu2 (A93);
A substitution of a glutamine residue at a position corresponding to position 126 of wild-type human Neu2 (Q126);
A substitution of an alanine residue at a position corresponding to position 242 of wild-type human Neu2 (A242);
(h) a substitution of a glutamine residue at a position corresponding to position 270 of wild-type human Neu2 (Q270);
The claims of the reference application encompass a sialidase that comprises a combination of the same substitutions as those recited in the instant claims 11 and 12. Finally, the claims of the reference application teach a method of treating cancer comprising administering to the subject a pharmaceutical composition along with an anti-CD20 antibody to the subject, such as rituximab.
The differences between the claim sets are as follows. While he claims of the reference application recite co-administering a cancer-targeting antibody, they do not recite conjugation of the sialidase to an antibody, nor do they recite nucleic acids encoding said conjugates, vectors comprising said nucleic acids and host cells comprising said vectors. Woods et al. disclose neuraminidase 2 (Neu2) conjugated to an antibody (i.e., a fusion protein) selected from trastuzumab, cetuximab, daratumumab, girentuximab, panitumumab, ofatumumab, and rituximab comprising a linker as well as nucleic acids encoding said fusion proteins, vectors comprising said nucleic acids and host cells comprising said vectors (see claims 1, 24, 25, 39-41, 77-92).
It would have been obvious to the person of ordinary skill in the art at the time of the filing of the invention to attach an antibody to Neu2 to form a fusion protein as taught in Woods et al. because sialidases such as Neu2 enhance the tumor fighting abilities cancer-targeting antibodies. Woods et al. teaches (see p. 43, lines 9-12):
Removal of cell-surface sialic acids by antibody-sialidase conjugate abolishes the interaction of sialylated glycans and NK-inhibitory receptors, and increases the binding between NK-activating receptor and its ligands, thereby enhancing the tumor cell susceptibility to NK cell-mediated ADCC.
The reference claims already suggested co-administering an antibody in the reference claims. The person of ordinary skill in the art would have been motivated by the direct suggestions of Woods et al. to conjugate the antibody to the Neu2. Furthermore, the person of ordinary skill in the art could have reasonably expected success in view of the explicit teachings and experimental evidence disclosed in Woods et al, who teach the successful conjugation of an antibody to Neu2 (see Example 2, pages 45-46). Thus, when read in light of Woods and colleagues, the instant claims are not patentably distinct from those of the reference application.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. Li et al. (WO2019136167) teach a modified Neu2 with substitutions M1D, V6Y, I187K and C332A, but they do not teach a mutation corresponding to position 62 or 93 of wild-type Neu2
RESULT 85
Query Match 99.3%; Score 2015; Length 380;
Best Local Similarity 99.5%;
Matches 378; Conservative 0; Mismatches 2; Indels 0; Gaps 0;
Qy 1 DASLPYLQKESVFQSGAHAYRIPALLYLPGQQSLLAFAEQRASKKDEHAELIVLRRGDYD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DASLPYLQKESVFQSGAHAYRIPALLYLPGQQSLLAFAEQRASKKDEHAELIVLRRGDYD 60
Qy 61 AGTHQVQWQAQEVVAQARLDGHRSMNPCPLYDEQTGTLFLFFIAIPGQVTEQQQLQTRAN 120
| |||||||||||||||||||||||||||||| |||||||||||||||||||||||||||
Db 61 APTHQVQWQAQEVVAQARLDGHRSMNPCPLYDAQTGTLFLFFIAIPGQVTEQQQLQTRAN 120
Qy 121 VTRLCQVTSTDHGRTWSSPRDLTDAAIGPAYREWSTFAVGPGHCLQLHDRARSLVVPAYA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VTRLCQVTSTDHGRTWSSPRDLTDAAIGPAYREWSTFAVGPGHCLQLHDRARSLVVPAYA 180
Qy 181 YRKLHPKQRPIPSAFCFLSHDHGRTWARGHFVAQDTLECQVAEVETGEQRVVTLNARSHL 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 YRKLHPKQRPIPSAFCFLSHDHGRTWARGHFVAQDTLECQVAEVETGEQRVVTLNARSHL 240
Qy 241 RARVQAQSTNDGLDFQESQLVKKLVEPPPQGCQGSVISFPSPRSGPGSPAQWLLYTHPTH 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 RARVQAQSTNDGLDFQESQLVKKLVEPPPQGCQGSVISFPSPRSGPGSPAQWLLYTHPTH 300
Qy 301 SWQRADLGAYLNPRPPAPEAWSEPVLLAKGSAAYSDLQSMGTGPDGSPLFGCLYEANDYE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 SWQRADLGAYLNPRPPAPEAWSEPVLLAKGSAAYSDLQSMGTGPDGSPLFGCLYEANDYE 360
Qy 361 EIVFLMFTLKQAFPAEYLPQ 380
||||||||||||||||||||
Db 361 EIVFLMFTLKQAFPAEYLPQ 380
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/CHRISTINA M BORGEEST/Primary Examiner, Art Unit 1675