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 .
1. Formal Matters
A. In the response filed 1/15/26, Applicants elected, without traverse, Group II, drawn to the indicated species. Therefore, this restriction is deemed proper and is made FINAL.
B. Claims 1, 2, 5, 8, 11, 14, 16, 18, 21-24, 26 and 29-35 are pending. Claims 1, 2, 11 and 14 are withdrawn as being drawn to non-elected inventions. Claim 22-24, 30-32 and 35 are indicated as withdrawn; however, based on the amendment to claim dependency, they are now part of elected invention. Therefore, claims 5, 8 and 16, 18, 21-24, 26 and 29-35 are the subject of this Office Action. Furthermore, upon further examination, all species have been examined.
2. Claim Objections
In claims 5, 16, 18, 21-24, 30-35, hyphenate “antigen binding” in all occurrences.
3. Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
A. Claims 5, 8, 16, 18, 21-24, 26 and 29-35 are rejected under 35 U.S.C. 103 as being unpatentable over Santich et al. (WO 2018/204873).
The claims are essentially drawn to increasing the efficacy of beta-radioimmunotherapy in a subject by administering an anti-DOTA x GD2 bispecific antibody, wherein the anti-DOTA binding fragment comprises a SADA polypeptide of either p53 or p63 and wherein a DOTA hapten is also administered.
Santich teaches a construct comprising a bispecific antibody comprising an anti-GD2 scFv and an anti-Bn-DOTA scFv linked to a SADA p53 tetramerization domain, wherein the construct is able to bind Bn-DOTA (Figure 2). See instant Figure 1B for comparison, as these are essentially the same constructs. This construct and the use of Bn-DOTA meet claims 5, 8 and 29.
Santich teaches the use of this construct in various PRIT treatment protocols (Figure 1A-C; claim 51) as well as the use of 177Lu as the beta particle-emitting epitope (177Lu-Bn-DOTA – paragraph [0047]), for the treatment of the cancers of claim 26 (claim 51; paragraphs [00280]-[00281]).
Santich does not teach claims 30-33 and 35. However, the advantage of the method of Santich, which specifically uses SADA, is that it allows for rapid elimination of unbound antibody, which provides specific delivery of the beta particle-emitting epitope that SADA conjugates exhibit reduced non-specific binding, decreased toxicity and/or improved renal clearance compared to a conjugate without a SADA domain (paragraph [005]). Furthermore, the lack of a clearing agent would make treatment quicker and safer. Regardless, case law has established that a compound and all of its properties are inseparable, as are its processes and yields (In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963)). This protocol, therefore, increases the efficacy of beta-immunotherapy.
Santich does not teach the specific administration steps in claim 5. However, the administration of a cold dose of a bispecific antibody which localizes to the tumor, followed at a later time by a hapten (e.g. Bn-DOTA) is the basis of PRIT. See Figure 1B of Santich, which teaches general administration times. Though specific times are not provided, including a second and third dose of hapten, where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 454, 105 USPQ 223,235, (CCPA 1955). Furthermore, "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." In re Boesch, 617 F.2d 272, 276, 205 USPQ 215, 219 (CCPA 1980). See also Merck & Co. v. Biocraft Labs. Inc., 874 F.2d 804, 809, 10 USPQ2d 1843, 1847-48 (Fed. Cir. 1989) (determination of suitable dosage amounts in diuretic compositions considered a matter of routine experimentation and, therefore, obvious) and E.I. DuPont de Nemours & Co. v. Synvina C.V., 904 F.3d 996, 1006 (Fed. Cir. 2018) (“it is not inventive to discover the optimum or workable ranges by routine experimentation.”).
Regarding claims 16, 18, 21-24 and 34, Santich teaches all of the claimed SEQ ID NOs, including the well-known (GGGGS)4 linker of SEQ ID NO:19. In addition, page 78 teaches SEQ ID NO:17 (below) with both the (GGGGS)4 linker and the TPLGDTTHT linker of SEQ ID NO:40.
Any of the claimed orders in claim 21-24 would have been obvious in order to maximize the protocol since, under KSR, it’s now apparent “obvious to try” may be an appropriate test in more situations than we previously contemplated. When there is motivation to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to anticipated success, it is likely the product not of innovation but of ordinary skill and common sense. In that instance the fact that a combination was obvious to try may show that it was obvious under § 103 (KSR Int’l Co. v. Teleflex Inc., 127 S. Ct. 1727 (2007), 82 USPQ2d 1385, 1397 (2007); 550 U.S. 398 (2007)).
SEQ ID NO:1
AC BFU55145;
XX
CC PN WO2018204873-A1.
XX
CC PD 08-NOV-2018.
XX
CC PF 04-MAY-2018; 2018WO-US031235.
XX
PR 05-MAY-2017; 2017US-0502151P.
XX
CC PA (SLOK ) SLOAN KETTERING INST CANCER RES.
XX
CC PI Santich BH, Ahmed M, Cheung NV;
XX
CC PS Example 1; SEQ ID NO 17; 181pp; English.
XX
SQ Sequence 559 AA;
Query Match 100.0%; Score 641; Length 559;
Best Local Similarity 100.0%;
Matches 119; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVESGPGVVQPGRSLRISCAVSGFSVTNYGVHWVRQPPGKCLEWLGVIWAGGITNYN 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 QVQLVESGPGVVQPGRSLRISCAVSGFSVTNYGVHWVRQPPGKCLEWLGVIWAGGITNYN 180
Qy 61 SAFMSRLTISKDNSKNTVYLQMNSLRAEDTAMYYCASRGGHYGYALDYWGQGTLVTVSS 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SAFMSRLTISKDNSKNTVYLQMNSLRAEDTAMYYCASRGGHYGYALDYWGQGTLVTVSS 239
SEQ ID NO:5
CC PN WO2018204873-A1
XX
CC PS Example 1; SEQ ID NO 17; 181pp; English.
XX
SQ Sequence 559 AA;
Query Match 100.0%; Score 543; Length 559;
Best Local Similarity 100.0%;
Matches 105; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EIVMTQTPATLSVSAGERVTITCKASQSVSNDVTWYQQKPGQAPRLLIYSASNRYSGVPA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EIVMTQTPATLSVSAGERVTITCKASQSVSNDVTWYQQKPGQAPRLLIYSASNRYSGVPA 60
Qy 61 RFSGSGYGTEFTFTISSVQSEDFAVYFCQQDYSSFGCGTKLEIKR 105
|||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGYGTEFTFTISSVQSEDFAVYFCQQDYSSFGCGTKLEIKR 105
SEQ ID NO:9
CC PN WO2018204873-A1.
XX
CC PS Example 1; SEQ ID NO 17; 181pp; English.
XX
SQ Sequence 559 AA;
Query Match 100.0%; Score 641; Length 559;
Best Local Similarity 100.0%;
Matches 119; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 HVQLVESGGGLVQPGGSLRLSCAASGFSLTDYGVHWVRQAPGKGLEWLGVIWSGGGTAYN 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 260 HVQLVESGGGLVQPGGSLRLSCAASGFSLTDYGVHWVRQAPGKGLEWLGVIWSGGGTAYN 319
Qy 61 TALISRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRGSYPYNYFDAWGCGTLVTVSS 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 320 TALISRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARRGSYPYNYFDAWGCGTLVTVSS 378
SEQ ID NO:17
CC PN WO2018204873-A1.
XX
CC PS Example 1; SEQ ID NO 37; 181pp; English.
XX
SQ Sequence 559 AA;
Query Match 100.0%; Score 644; Length 559;
Best Local Similarity 100.0%;
Matches 119; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 HVKLQESGPGLVQPSQSLSLTCTVSGFSLTDYGVHWVRQSPGKGLEWLGVIWSGGGTAYN 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 260 HVKLQESGPGLVQPSQSLSLTCTVSGFSLTDYGVHWVRQSPGKGLEWLGVIWSGGGTAYN 319
Qy 61 TALISRLNIYRDNSKNQVFLEMNSLQAEDTAMYYCARRGSYPYNYFDAWGCGTTVTVSS 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 320 TALISRLNIYRDNSKNQVFLEMNSLQAEDTAMYYCARRGSYPYNYFDAWGCGTTVTVSS 378
SEQ ID NO:13
CC PN WO2018204873-A1.
XX
CC PS Example 1; SEQ ID NO 17; 181pp; English.
XX
SQ Sequence 559 AA;
Query Match 100.0%; Score 594; Length 559;
Best Local Similarity 100.0%;
Matches 110; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTASNYANWVQQKPGQCPRGLIGGHNNRPPGV 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 394 QAVVTQEPSLTVSPGGTVTLTCGSSTGAVTASNYANWVQQKPGQCPRGLIGGHNNRPPGV 453
Qy 61 PARFSGSLLGGKAALTLLGAQPEDEAEYYCALWYSDHWVIGGGTKLTVLG 110
||||||||||||||||||||||||||||||||||||||||||||||||||
Db 454 PARFSGSLLGGKAALTLLGAQPEDEAEYYCALWYSDHWVIGGGTKLTVLG 503
SEQ ID NO:18
CC PN WO2018204873-A1.
XX
CC PS Example 1; SEQ ID NO 37; 181pp; English.
XX
SQ Sequence 559 AA;
Query Match 100.0%; Score 592; Length 559;
Best Local Similarity 100.0%;
Matches 110; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QAVVIQESALTTPPGETVTLTCGSSTGAVTASNYANWVQEKPDHCFTGLIGGHNNRPPGV 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 394 QAVVIQESALTTPPGETVTLTCGSSTGAVTASNYANWVQEKPDHCFTGLIGGHNNRPPGV 453
Qy 61 PARFSGSLIGDKAALTIAGTQTEDEAIYFCALWYSDHWVIGGGTRLTVLG 110
||||||||||||||||||||||||||||||||||||||||||||||||||
Db 454 PARFSGSLIGDKAALTIAGTQTEDEAIYFCALWYSDHWVIGGGTRLTVLG 503
SEQ ID NO:36
CC PN WO2018204873-A1.
XX
CC PS Claim 7; SEQ ID NO 1; 181pp; English.
XX
SQ Sequence 39 AA;
Query Match 100.0%; Score 201; Length 39;
Best Local Similarity 100.0%;
Matches 39; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 KPLDGEYFTLQIRGRERFEMFRELNEALELKDAQAGKEP 39
|||||||||||||||||||||||||||||||||||||||
Db 1 KPLDGEYFTLQIRGRERFEMFRELNEALELKDAQAGKEP 39
SEQ ID NO:37
CC PN WO2018204873-A1.
XX
CC PS Claim 7; SEQ ID NO 3; 181pp; English.
XX
SQ Sequence 57 AA;
Query Match 100.0%; Score 296; Length 57;
Best Local Similarity 100.0%;
Matches 57; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RSPDDELLYLPVRGRETYEMLLKIKESLELMQYLPQHTIETYRQQQQQQHQHLLQKQ 57
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 RSPDDELLYLPVRGRETYEMLLKIKESLELMQYLPQHTIETYRQQQQQQHQHLLQKQ 57
B. Claims 5, 8, 16, 18, 21-24, 26 and 29-35 are rejected under 35 U.S.C. 103 as being unpatentable over Cheal et al. in view of Santich et al. (WO 2018/204873).
The claims and Santich (WO) are discussed above. Cheal teaches PRIT using a GD2 x anti-DOTA bispecific antibody followed by treatment with 177Lu-DOTA for treatment of neuroblastoma (Abstract). Cheal does not teach the use of the bispecific antibody fused to SADA (p53 or p63) domains. However, Santich teaches essentially the same treatment as Cheal with the inclusion of a SADA domain and also teaches that SADA conjugates exhibit reduced non-specific binding, decreased toxicity and/or improved renal clearance compared to a conjugate without a SADA domain (paragraph [005]). Furthermore, the lack of a clearing agent would make treatment quicker and safer.
Neither reference teaches claims 30-33 and 35. However, the advantage of the method of Santich, which specifically uses SADA, is that it allows for rapid elimination of unbound antibody, which provides specific delivery of the beta particle-emitting epitope that SADA conjugates exhibit reduced non-specific binding, decreased toxicity and/or improved renal clearance compared to a conjugate without a SADA domain (paragraph [005]). Furthermore, the lack of a clearing agent would make treatment quicker and safer. Regardless, case law has established that a compound and all of its properties are inseparable, as are its processes and yields (In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963)). This protocol, therefore, increases the efficacy of beta-immunotherapy.
Neither reference teaches the specific administration protocol in claim 5. However, this is not inventive (In re Aller; In re Boesch; Merck & Co. v. Biocraft Labs. Inc.; E.I. DuPont de Nemours & Co. v. Synvina C.V.).
Regarding claims 16, 18, 21-24 and 34, Santich teaches all of the claimed SEQ ID NOs, including the well-known (GGGGS)4 linker of SEQ ID NO:19. In addition, page 78 teaches SEQ ID NO:17 (below) with both the (GGGGS)4 linker and the TPLGDTTHT linker of SEQ ID NO:40 (KSR Int’l Co. v. Teleflex Inc., 127 S. Ct. 1727 (2007), 82 USPQ2d 1385, 1397 (2007); 550 U.S. 398 (2007)).
C. Claims 5, 8, 26, 29-33 and 35 are rejected under 35 U.S.C. 103 as being obvious over Santich et al. (JNM - cited on the IDS filed 7/25/24).
The claims are essentially drawn to increasing the efficacy of beta-radioimmunotherapy in a subject by administering an anti-DOTA x GD2 bispecific antibody, wherein the anti-DOTA binding fragment comprises a SADA polypeptide of either p53 or p63 and wherein a DOTA hapten is also administered.
Santich teaches a 2-step PRIT which uses an anti-GD2 x anti-DOTA bispecific antibody (first sentence under “Methods) using a P53-derived tetramerization sequence as the SADA polypeptide (first sentence under “Results”). Santich also teaches the use of 177Lu as the beta particle-emitting epitope (sentences 7-8 under “Results”), meeting claim 8, used to treat neuroblastoma and SCLC (lines 4-5 under “Methods”), meeting claim 26. Proteus-DOTA is also taught (line 11 under “Results”), meeting claim 29.
Santich does not teach claims 30-33 and 35. However, the advantage of the method of Santich, which specifically uses SADA, allows for rapid elimination of unbound antibody, which provides specific delivery of the beta particle-emitting epitope “without any observable treatment-related toxicity” (Conclusion), “including to kidneys, liver, spleen, or hematopoietic system including bone marrow” (lines 9-11 under “Results”). Regardless, case law has established that a compound and all of its properties are inseparable, as are its processes and yields (In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963)). This protocol, therefore, increases the efficacy of beta-immunotherapy.
Santich does not teach the specific administration steps in claim 5. However, the administration of a cold dose of a bispecific antibody which localizes to the tumor, followed at a later time by a hapten (e.g. Bn-DOTA) is the basis of PRIT. Though specific times are not provided, including a second and third dose of hapten, this is not inventive (In re Aller; In re Boesch; Merck & Co. v. Biocraft Labs. Inc.; E.I. DuPont de Nemours & Co. v. Synvina C.V.)
D. Claims 16, 18, 21-24 and 34 are rejected under 35 U.S.C. 103 as being obvious over Santich et al. (JNM) in view of Santich (WO).
The teachings of both Santich (JNM) and Santich (WO) are seen above. Santich (JNM) does not teach the sequences in claims 16, 18 and 21-24. However, Santich (WO) teaches all of the claimed SEQ ID NOs, including the well-known (GGGGS)4 linker of SEQ ID NO:19. In addition, page 78 teaches SEQ ID NO:17 (below) with both the (GGGGS)4 linker and the TPLGDTTHT linker of SEQ ID NO:40 (KSR Int’l Co. v. Teleflex Inc., 127 S. Ct. 1727 (2007), 82 USPQ2d 1385, 1397 (2007); 550 U.S. 398 (2007)).
E. Claims 5, 8, 26 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Cheal et al. (cited on the IDS filed 7/25/24) in view of Santich et al. (JNM).
The claims, Santich and Cheal are discussed above. Cheal does not teach the use of the bispecific antibody fused to SADA (p53 or p63) domains. However, Santich teaches essentially the same treatment as Cheal with the inclusion of a SADA domain. The inclusion of SADA allows for rapid clearance of BsAb from the blood within 48 hours without the need to administer a clearing agent, making treatment quicker and safer.
Neither reference teaches the specific administration protocol in claim 5. However, this is not inventive (In re Aller; In re Boesch; Merck & Co. v. Biocraft Labs. Inc.; E.I. DuPont de Nemours & Co. v. Synvina C.V.).
4. Nonstatutory 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.
A. Claims 5, 8, 16, 18, 21-24, 26 and 30-35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 8, 9 and 10 of U.S. Patent No. 12,343,401 (18/153,228) in view of Santich et al. (WO). Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘401 claims are drawn to treating cancer in a patient by administering the bispecific antibody of the instant claims (GD2 x Bn-DOTA - see claims 1, 8 and 9), whereas the instant claims are drawn to a method of increasing efficacy of therapy using the identical compound. SEQ ID NO:1 of ‘401 is identical to instant SEQ ID NO:36 and the 6 CDR SEQ ID NOs encode SEQ ID NO:17 and 18 of ‘401.
The only essential difference is that the instant claims use a protocol which provides multiple doses of DOTA hapten. However, Figure 1B of Santich (WO) teaches a general administration protocol which requires a time interval between antibody and hapten administration. Neither ‘401 nor the WO teaches the specific administration protocol in claim 5. However, as discussed under 35 USC 103, this is not inventive (In re Aller; In re Boesch; Merck & Co. v. Biocraft Labs. Inc.; E.I. DuPont de Nemours & Co. v. Synvina C.V.).
The ‘401 patent does not teach 177Lu-Bn-DOTA, nor the instantly claimed sequences. However, as discussed above under 35 USC 103, Santich (WO) does. See also KSR Int’l Co. v. Teleflex Inc., 127 S. Ct. 1727 (2007), 82 USPQ2d 1385, 1397 (2007); 550 U.S. 398 (2007).
Neither reference teaches claims 30-33 and 35. However, the advantage of the method of Santich, which specifically uses SADA, is that it allows for rapid elimination of unbound antibody, which provides specific delivery of the beta particle-emitting epitope that SADA conjugates exhibit reduced non-specific binding, decreased toxicity and/or improved renal clearance compared to a conjugate without a SADA domain (see also paragraph [005] of Santich (WO)). Furthermore, the lack of a clearing agent would make treatment quicker and safer. Regardless, case law has established that a compound and all of its properties are inseparable, as are its processes and yields (In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963)). This protocol, therefore, increases the efficacy of beta-immunotherapy.
B. Claims 5, 8, 16, 18, 21-24, 26 and 30-35 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 5, 7 and 8 of U.S. Patent No. 11,583,588 (16/609,401) in view of Santich et al. (WO). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims are drawn to a method of using the composition of claim 1 of ‘588. It is noted that SEQ ID NO:1 of ‘588 is identical to instant SEQ ID NO:36 and the 6 CDR SEQ ID NOs encode SEQ ID NO:17 and 18 of ‘588. The SADA tetramer has a size of greater than 150 KDa, whereas the monomer is less than 70 KDa (paragraphs [009] and [0010] of Santich (WO).
The only essential difference is that the instant claims use a protocol which provides multiple doses of DOTA hapten. However, Figure 1B of Santich (WO) teaches a general administration protocol which requires a time interval between antibody and hapten administration. Neither ‘588 nor the WO teaches the specific administration protocol in claim 5. However, as discussed under 35 USC 103, this is not inventive (In re Aller; In re Boesch; Merck & Co. v. Biocraft Labs. Inc.; E.I. DuPont de Nemours & Co. v. Synvina C.V.).
The ‘588 patent does not teach 177Lu-Bn-DOTA, nor the instantly claimed sequences. However, as discussed above under 35 USC 103, Santich (WO) does. See also KSR Int’l Co. v. Teleflex Inc., 127 S. Ct. 1727 (2007), 82 USPQ2d 1385, 1397 (2007); 550 U.S. 398 (2007).
Neither reference teaches claims 30-33 and 35. However, the advantage of the method of Santich, which specifically uses SADA, is that it allows for rapid elimination of unbound antibody, which provides specific delivery of the beta particle-emitting epitope that SADA conjugates exhibit reduced non-specific binding, decreased toxicity and/or improved renal clearance compared to a conjugate without a SADA domain (see also paragraph [005] of Santich (WO)). Furthermore, the lack of a clearing agent would make treatment quicker and safer. Regardless, case law has established that a compound and all of its properties are inseparable, as are its processes and yields (In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963)). This protocol, therefore, increases the efficacy of beta-immunotherapy.
C. Claims 5, 8 and 16, 18, 21-24, 26 and 29-35 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4-6, 8, 11, 13-15 and 18-20 of copending Application No. 19/231,378 (US 2025/0295794 (reference application) in view of Santich et al. (WO). Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims are drawn to nucleic acids encoding the SADA polypeptide of the instant claims. The p53-containing SADA polypeptide, which inherently forms a tetramer, has a size of greater than 150 KDa, whereas the monomer is less than 70 KDa (paragraphs [009] and [0010] of Santich (WO). SEQ ID NO:1 of the copending application is identical to instant SEQ ID NO:36. The polypeptide of copending claims 8, 11 and 13-15 meet the bispecific GD2 x Bn-DOTA antibody of the instant claims.
The only essential difference is that the instant claims use a protocol which provides multiple doses of DOTA hapten. However, Figure 1B of Santich (WO) teaches a general administration protocol which requires a time interval between antibody and hapten administration. Neither the copending application, nor the WO teaches the specific administration protocol in claim 5. However, as discussed under 35 USC 103, this is not inventive (In re Aller; In re Boesch; Merck & Co. v. Biocraft Labs. Inc.; E.I. DuPont de Nemours & Co. v. Synvina C.V.).
The copending application does not teach 177Lu-Bn-DOTA, nor the instantly claimed sequences. However, as discussed above under 35 USC 103, Santich (WO) does. See also KSR Int’l Co. v. Teleflex Inc., 127 S. Ct. 1727 (2007), 82 USPQ2d 1385, 1397 (2007); 550 U.S. 398 (2007).
Neither the copending application, nor the WO teaches claims 30-33 and 35. However, the advantage of the method of Santich (WO), which specifically uses SADA, is that it allows for rapid elimination of unbound antibody, which provides specific delivery of the beta particle-emitting epitope that SADA conjugates exhibit reduced non-specific binding, decreased toxicity and/or improved renal clearance compared to a conjugate without a SADA domain (see also paragraph [005] of Santich (WO)). Furthermore, the lack of a clearing agent would make treatment quicker and safer. Regardless, case law has established that a compound and all of its properties are inseparable, as are its processes and yields (In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963)). This protocol, therefore, increases the efficacy of beta-immunotherapy.
Therefore, it would have been obvious at the time of the instant invention to have used the polypeptide complex encoded by the nucleic acid of the copending application and expressed in that system, in the method of Santich (WO) in light of the motivation provided by Santich (WO) to improve the safety and, therefore, efficacy of beta-immunotherapy via specific targeting of the hapten, thereby reducing potentially significant side effects normally associated with PRIT.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
5. Conclusion
No claim is allowable.
Advisory information
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/ROBERT S LANDSMAN/Primary Examiner, Art Unit 1647