Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 09/17/2025 has been entered.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 47, and 51-61 have an effective filing date of 11 SEP 2015.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 7/21/2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Election/Restriction
In the response filed on 5/10/2024 Applicant elected, with traverse:
Cetuximab
The heavy chain CDRs of cetuximab
The light chain CDRs of cetuximab
Imaging agent.
Status of Claims
Claims 59-60 are withdrawn from further consideration by Examiner under 37 CFR 1.142(b) as being drawn to non-elected species.
Claims 47, 51-58, and 61 are currently pending and presented for examination on the merits.
Claim 47 is amended.
Claims 1-46, and 48-50 are canceled.
Rejections Withdrawn
The rejection filed under 35 U.S.C. 103 is withdrawn in view of Applicant’s amendments to claims.
The rejections filed under Double Patenting are withdrawn in view of Applicant’s amendments.
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.
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 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.
Claims 47, 51, 52, and 54 are rejected under 35 U.S.C. 103 as being unpatentable over Goletz et al (WO 2008028686), Govindappa et al (US 20130287802, previous OA), and further in view of Veisi et al (Development and Evaluation of a Cetuximab-based Humanized Single Chain Antibody Against EGFR-overexpressing Tumors, Drug Res, 65: 624, 2015).
In regard to claim 47, Goletz et al teaches an antibody molecule composition that originates from cetuximab [6th Paragraph, pg. 54]. Goletz et al further teaches cetuximab heavy chain [Example 4, pg. 63]. A comparison of Goletz variable Heavy chain and instant claims SEQ ID NO: 3 (CDR1 at amino acids 26-33, CDR2 at amino acids 51-57, and CDR3 at amino acids 96-108) is shown below.
Instant claims SEQ ID NO: 3 (CDR1 at amino acids 26-33, CDR2 at amino acids 51-57, and CDR3 at amino acids 96-108) and Cetuximab heavy chain of Goletz et al is shown below.
Query Match 83.8%; Score 131.5; Length 118;
Best Local Similarity 33.7%;
Matches 28; Conservative 0; Mismatches 0; Indels 55; Gaps 2;
Qy 1 GFSLTNYG-----------------IWSGGNT---------------------------- 15
|||||||| |||||||
Db 26 GFSLTNYGVHWVRQSPGKGLEWLGVIWSGGNTDYNTPFTSRLSINKDNSKSQVFFKMNSL 85
Qy 16 ----------ARALTYYDYEFAY 28
|||||||||||||
Db 86 QSNDTAIYYCARALTYYDYEFAY 108
Goletz et al further teaches cetuximab light chain [Example 4, pg. 63]. A comparison of Goletz cetuximab light chain and instant claims SEQ ID NO: 3 (CDR1 at amino acids 146-151, CDR2 at amino acids 169-171, and CDR3 at amino acids 208-216) is shown below.
Instant claims SEQ ID NO: 3 (CDR1 at amino acids 146-151, CDR2 at amino acids 169-171, and CDR3 at amino acids 208-216) and Cetuximab light chain of Goletz et al is shown below.
Query Match 93.1%; Score 182.4; Length 108;
Best Local Similarity 49.3%;
Matches 35; Conservative 0; Mismatches 0; Indels 36; Gaps 1;
Qy 1 QSIGTNIHWYQQRTNGSPRLLIKYAS---------------------------------- 26
||||||||||||||||||||||||||
Db 27 QSIGTNIHWYQQRTNGSPRLLIKYASESISGIPSRFSGSGSGTDFTLSINSVESEDIADY 86
Qy 27 --QQNNNWPTT 35
|||||||||
Db 87 YCQQNNNWPTT 97
Goletz et al does not specifically teach an antibody framework of SEQ ID NO:1 and SEQ ID NO: 2. However, this deficiency is made up in the teachings of Govindappa et al.
Govindappa et al teaches the antibody chain acceptor framework SEQ ID NO: 35 [0091]. A comparison of instant SEQ ID NO: 1 and SEQ ID NO: 35 of Govindappa et al is shown below.
Instant SEQ ID NO: 1 and SEQ ID NO: 35 of Govindappa et al.
Query Match 98.1%; Score 2225; Length 450;
Best Local Similarity 94.7%;
Matches 426; Conservative 0; Mismatches 0; Indels 24; Gaps 3;
Qy 1 EVQLLESGGDLVQPGGSLRLSCAASGFTF-----SWVRQAPGKGLEWVS----------Y 45
||||||||||||||||||||||||||||| ||||||||||||||| |
Db 1 EVQLLESGGDLVQPGGSLRLSCAASGFTFSNYAMSWVRQAPGKGLEWVSAITPSGGSTNY 60
Qy 46 ADSVKGRFTISRDNSQNTLYLQMNSLRVEDTAVYICGRVP---------WGQGTLVTVSS 96
|||||||||||||||||||||||||||||||||||||||| |||||||||||
Db 61 ADSVKGRFTISRDNSQNTLYLQMNSLRVEDTAVYICGRVPYRSTWYPLYWGQGTLVTVSS 120
Qy 97 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 156
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
Qy 157 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 216
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 240
Qy 217 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 276
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
Qy 277 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE 336
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDE 360
Qy 337 LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 396
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 LTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
Qy 397 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 426
||||||||||||||||||||||||||||||
Db 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
Govindappa et al further teaches the antibody chain acceptor framework SEQ ID NO: 36 [0091]. A comparison of instant SEQ ID NO: 2 and SEQ ID NO: 36 of Govindappa et al is shown below.
Instant SEQ ID NO: 2 and SEQ ID NO: 36 of Govindappa et al.
Query Match 96.0%; Score 959.5; Length 214;
Best Local Similarity 90.2%;
Matches 193; Conservative 0; Mismatches 0; Indels 21; Gaps 3;
Qy 1 DIQMTQSPSSLSASVGDRVTITCRASQ-------WFQQKPGKAPKSLIY-------KVPT 46
||||||||||||||||||||||||||| ||||||||||||||| ||||
Db 1 DIQMTQSPSSLSASVGDRVTITCRASQDISNYLAWFQQKPGKAPKSLIYAASSLHSKVPT 60
Qy 47 QFSGSGSGTDFTLTISSLQPEDFATYYCLQ-------FGGGTKVEIKRTVAAPSVFIFPP 99
|||||||||||||||||||||||||||||| |||||||||||||||||||||||
Db 61 QFSGSGSGTDFTLTISSLQPEDFATYYCLQYSTYPITFGGGTKVEIKRTVAAPSVFIFPP 120
Qy 100 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 159
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
Qy 160 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 193
||||||||||||||||||||||||||||||||||
Db 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
Goletz et al does not specifically teach grafting cetuximab CDRs to an acceptor framework. However, this deficiency is made up in the teachings of Veisi et al.
Veisi et al teaches an antibody made from grafting cetuximab CDRs to an acceptor framework [Abstract]. Veisi et al further teaches by grafting the cetuximab CDRs to an acceptor framework displayed reduced potential immunogenicity as well as enhanced cytotoxic effect on EGFR-overexpressing tumor cells [Abstract].
One of ordinary skill, before the effective filing date, would have been motivated to combine Goletz’s antibody comprising the heavy and light chain CDRs of cetuximab, with Govindappa’s antibody heavy/light chain acceptor framework, with Veisi’s method of grafting cetuximab heavy/light chain CDRs to an antibody acceptor framework. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine the teachings of Goletz, Govindappa, and Veisi’s methods for an antibody with heavy chain acceptor framework of SEQ ID NO: 1 with amino acids 31-35, replaced with CDR1 of SEQ ID NO: 3 at amino acids 26-33, amino acids 50-59 replaced with CDR2 of SEQ ID NO: 3 at amino acids 51-57, and amino acids 101-109 replaced with CDR3 of SEQ ID NO: 3 at amino acids 96-108, and light chain acceptor framework of SEQ ID NO: 2 with amino acids 28-34 replaced with CDR1 of SEQ ID NO: 3 at amino acids 146-151, amino acids 50-56 replaced with CDR2 of SEQ ID NO: 3 at amino acids 169-171, and amino acids 91-97 replaced with CDRs of SEQ ID NO: 3 at amino acids 208-216. Motivated by the teachings of Veisi et al teaches grafting an antibodies CDRs reduces the potential immunogenicity as well as enhanced cytotoxic effect on cells.
In regards to claims 51-52, the isoelectric point would be an inherent property of the engineered antibody.
With respect to claim 54, at [0146], Govindappa et al. teach that biological agents may be formulated with pharmaceutically acceptable carriers.
Claims 53, 55-58, and 61 are rejected under 35 U.S.C. 103 as being unpatentable over Goletz et al (WO 2008028686), Govindappa et al (US 20130287802), Veisi et al (Development and Evaluation of a Cetuximab-based Humanized Single Chain Antibody Against EGFR-overexpressing Tumors, Drug Res, 65: 624, 2015) as applied to claims 47, 51, 52, and 54 above, and further in view of Sihver et al (Radiolabeled Cetuximab Conjugates for EGFR Targeted Cancer Diagnostics and Therapy, Pharmaceuticals 2014, 7, 311-338, previous OA).
The teachings of Goletz et al, Govindappa et al, and Veisi et al are discussed above.
Goletz et al does not specifically teach cetuximab crossing the blood-brain-barrier (BBB) and being conjugated to an agent. However, this deficiency is made up in the teachings of Sihver et al.
In regards to claims 53, 55, and 56, Sihver et al shows cetuximab passing through the blood-brain-barrier [1st Paragraph, pg. 325].
In regards to claims 57-58, and 61, Sihver et al further teaches cetuximab for the imaging and treatment of cancers [Abstract, pg. 312]. Sihver et al further teaches radionucleotides conjugated to cetuximab [Abstract, pg. 311]. Sihver et al further teaches 131I-labeled cetuximab applied to monitor and treat brain metastases [1st Paragraph, pg. 325].
One of ordinary skill, before the effective filing date, would have been motivated to combine Goletz’s antibody comprising the heavy and light chain CDRs of cetuximab, with Govindappa’s antibody heavy/light chain acceptor framework, with Veisi’s method of grafting cetuximab heavy/light chain CDRs to an antibody acceptor framework, with Sihver’s method of conjugating cetuximab to an imaging agent. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine the teachings of Goletz, Govindappa, and Veisi’s methods for an antibody with heavy chain acceptor framework of SEQ ID NO: 1 with amino acids 31-35, replaced with CDR1 of SEQ ID NO: 3 at amino acids 26-33, amino acids 50-59 replaced with CDR2 of SEQ ID NO: 3 at amino acids 51-57, and amino acids 101-109 replaced with CDR3 of SEQ ID NO: 3 at amino acids 96-108, and light chain acceptor framework of SEQ ID NO: 2 with amino acids 28-34 replaced with CDR1 of SEQ ID NO: 3 at amino acids 146-151, amino acids 50-56 replaced with CDR2 of SEQ ID NO: 3 at amino acids 169-171, and amino acids 91-97 replaced with CDRs of SEQ ID NO: 3 at amino acids 208-216 and conjugate the antibody to an imaging agent. Motivated by the teachings of Veisi et al teaches grafting an antibodies CDRs reduces the potential immunogenicity as well as enhanced cytotoxic effect on cells.
Applicant’s Arguments:
Applicant respectfully traverses the rejections
Govindappa fails to disclose or suggest an antibody crossing the blood brain barrier (BBB) and comprising an imaging agent but cites Sihver as describing an EGFR antibody cetuximab for imaging and treating cancer. (Office Action, page 6). The Office asserts it would have been prima facie obvious and one of ordinary skill would have been motivated to apply Govindappa's antibody comprising framework SEQ ID NO: 1 and 2 and cetuximab, with Jolliffe's method of grafting CDRs, Sihver's cetuximab conjugated to an imaging agent and Lazar's cetuximab comprising SEQ ID NO: 3. (Office Action, page 9).
Applicant respectfully disagrees.
Applicant respectfully submits none of the references, i.e., Govindappa, Jolliffe, Sihver, or Lazar, alone or in combination, disclose or suggest grafting the six CDRs with defined amino acid sequences as recited in claim 47.
Govindappa fails to disclose or suggest replacing CDRs of an antibody, much less an antibody with the ability to cross the BBB. Jolliffe does not cure the deficiencies of Govindappa. Jolliffe discloses a CDR-grafted antibody capable of binding to the CD4 antigen. (Jolliffe, ¶ [0060]). Jolliffe does not disclose or suggest a CDR-grafted antibody with the claimed amino acid sequence or one capable of binding to EGFR or crossing the BBB. (Specification, ¶ [0059]).
Regarding the Office's assertion that since the cited references describe an identical structure, the properties disclosed and/or claimed by the Applicant - specifically, the ability to cross the BBB - are necessarily present (Office Action, page 11), Applicant respectfully disagrees. The BBB poses a major obstacle to the systemic delivery of biologic therapeutic and diagnostic agents for the treatment of neurological diseases. (Specification as filed, ¶ [0003]).
Examiner’s Response:
One of ordinary skill, before the effective filing date, would have been motivated to combine Goletz’s antibody comprising the heavy and light chain CDRs of cetuximab, with Govindappa’s antibody heavy/light chain acceptor framework, with Veisi’s method of grafting cetuximab heavy/light chain CDRs to an antibody acceptor framework. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine the teachings of Goletz, Govindappa, and Veisi’s methods for an antibody with heavy chain acceptor framework of SEQ ID NO: 1 with amino acids 31-35, replaced with CDR1 of SEQ ID NO: 3 at amino acids 26-33, amino acids 50-59 replaced with CDR2 of SEQ ID NO: 3 at amino acids 51-57, and amino acids 101-109 replaced with CDR3 of SEQ ID NO: 3 at amino acids 96-108, and light chain acceptor framework of SEQ ID NO: 2 with amino acids 28-34 replaced with CDR1 of SEQ ID NO: 3 at amino acids 146-151, amino acids 50-56 replaced with CDR2 of SEQ ID NO: 3 at amino acids 169-171, and amino acids 91-97 replaced with CDRs of SEQ ID NO: 3 at amino acids 208-216. Motivated by the teachings of Veisi et al teaches grafting an antibodies CDRs reduces the potential immunogenicity as well as enhanced cytotoxic effect on cells.
Applicant states, “none of the references, i.e., Govindappa, Jolliffe, Sihver, or Lazar, alone or in combination, disclose or suggest grafting the six CDRs with defined amino acid sequences as recited in claim 47”.
Veisi et al teaches an antibody made from grafting cetuximab CDRs to an acceptor framework [Abstract]. Veisi et al further teaches by grafting the cetuximab CDRs to an acceptor framework displayed reduced potential immunogenicity as well as enhanced cytotoxic effect on EGFR-overexpressing tumor cells [Abstract].
One of ordinary skill in the art would recognize that Veisi et al teaches grafting cetuximab CDRs to antibody acceptor frameworks.
Applicant states, “the cited references describe an identical structure, the properties disclosed and/or claimed by the Applicant - specifically, the ability to cross the BBB - are necessarily present (Office Action, page 11), Applicant respectfully disagrees.”
Sihver et al further teaches cetuximab for the imaging and treatment of cancers [Abstract, pg. 312]. Sihver et al further teaches radionucleotides conjugated to cetuximab [Abstract, pg. 311]. Sihver et al further teaches 131I-labeled cetuximab applied to monitor and treat brain metastases [1st Paragraph, pg. 325].
One of ordinary skill would be recognize that an identical antibody would inherently have the same properties and limitations.
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 47, 51-58, and 61 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11028155 ('155) in view of Goletz et al (WO 2008028686), Govindappa et al (US 20130287802, previous OA), Veisi et al (Development and Evaluation of a Cetuximab-based Humanized Single Chain Antibody Against EGFR-overexpressing Tumors, Drug Res, 65: 624, 2015), and Sihver et al (Radiolabeled Cetuximab Conjugates for EGFR Targeted Cancer Diagnostics and Therapy, Pharmaceuticals 2014, 7, 311-338, previous OA).
The teachings of Goletz et al, Govindappa et al, Veisi et al, and Sihver et al are discussed above.
Claim 47 is directed to an invention that is not patentably distinct from claim 1 of ‘155. Specifically, an antibody comprising acceptor framework SEQ ID NOs: 1 & 2. Wherein, VH acceptor framework SEQ ID NO: 1 CDRs are replace at 31-35, 50-59, and 101-109, and VL acceptor framework SEQ ID NO: 2 CDRs are replaced at 28-34, 50-56, and 91-97, are replaced with desired antibody.
Goletz et al teaches an antibody molecule composition that originates from cetuximab [6th Paragraph, pg. 54]. Goletz et al further teaches cetuximab heavy chain [Example 4, pg. 63]. A comparison of Goletz variable Heavy chain and instant claims SEQ ID NO: 3 (CDR1 at amino acids 26-33, CDR2 at amino acids 51-57, and CDR3 at amino acids 96-108) is shown above.
Goletz et al further teaches cetuximab light chain [Example 4, pg. 63]. A comparison of Goletz cetuximab light chain and instant claims SEQ ID NO: 3 (CDR1 at amino acids 146-151, CDR2 at amino acids 169-171, and CDR3 at amino acids 208-216) is shown above.
Veisi et al teaches an antibody made from grafting cetuximab CDRs to an acceptor framework [Abstract]. Veisi et al further teaches by grafting the cetuximab CDRs to an acceptor framework displayed reduced potential immunogenicity as well as enhanced cytotoxic effect on EGFR-overexpressing tumor cells [Abstract].
One of ordinary skill would have been motivated to apply Goletz’s antibody comprising the heavy and light chain CDRs of cetuximab, with Veisi’s method of grafting cetuximab heavy/light chain CDRs to an antibody acceptor framework, with ‘155 acceptor framework.
In regards to claims 51-52, the isoelectric point would be an inherent property of the engineered antibody.
The principle of law states from MPEP 2144.05: "The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."(Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382); Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here 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, 456, 105 USPQ 233, 235 (CCPA 1955).
In regards to claim 53, Sihver et al shows cetuximab passing through the blood-brain-barrier [1st Paragraph, pg. 325].
In regards to claims 54-55, and 56, appear to contain statement’s reciting “inherent property of crossing the blood brain barrier and delivered to the brain. See MPEP 2112 for discussion of “inherent use”. "In relying upon the theory of inherency, the examiner must provide a basis in fact and/or technical reasoning to reasonably support the determination that the allegedly inherent characteristic necessarily flows from the teachings of the applied prior art." Ex parte Levy, 17 USPQ2d 1461, 1464 (Bd. Pat. App. & Inter. 1990) (emphasis in original). In PAR Pharmaceutical, Inc. v. TWI Pharmaceuticals, Inc., 773 F.3d 1186, 112 USPQ2d 1945 (Fed. Cir. 2014), the Federal Circuit remanded a decision to the district court because the record did not present sufficient evidence to prove inherency in the context of obviousness. The district court concluded the pharmacokinetic parameters of a claim are inherent properties of the obvious formulation. The Federal Circuit stated that while "inherency may support a missing claim limitation in an obviousness analysis", "the use of inherency, a doctrine originally rooted in anticipation, must be carefully circumscribed in the context of obviousness." Id. at 1194-95, 112 USPQ2d at 1952. "[I]n order to rely on inherency to establish the existence of a claim limitation in the prior art in an obviousness analysis – the limitation at issue necessarily must be present, or the natural result of the combination of elements explicitly disclosed by the prior art." Id. at 1195-96, 112 USPQ2d at 1952. But see, Persion Pharms. LLC v. Alvogen Malta Operations LTD., 945 F.3d 1184, 1191, 2019 USPQ2d 494084 (Fed. Cir. 2019), where the court stated that a proper finding of inherency does not require that all limitations are taught in a single reference, and that inherency may meet a missing claim limitation when the limitation is "the natural result of the combination of prior art elements." (emphasis in original). The court found that pharmacokinetic limitations of the asserted claims were inherently met by combining prior art references because the limitations were necessarily present in the prior art combination. Id. See also Hospira, Inc. v. Fresenius Kabi USA, LLC, 946 F.3d 1322, 1329-32, 2020 USPQ2d 6227 (Fed. Cir. 2020).
In regards to claims 57-58, and 61, Sihver et al further teaches cetuximab for the imaging and treatment of cancers [Abstract, pg. 312]. Sihver et al further teaches radionucleotides conjugated to cetuximab [Abstract, pg. 311]. Sihver et al further teaches 131I-labeled cetuximab applied to monitor and treat brain metastases [1st Paragraph, pg. 325].
Applicant’s Arguments:
Applicant provides a terminal disclaimer over U.S. Patent 11028155 along with accompanying fee.
Examiner’s Response:
No terminal disclaimer has been received.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DENNIS JOHN SULLIVAN whose telephone number is (571)272-0509. The examiner can normally be reached Mon - Fri: 7:30AM - 4:30PM.
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/DENNIS J SULLIVAN/Examiner, Art Unit 1642
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642