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 .
Claim Status
Applicant’s reply filed on 10/21/2025 is acknowledged. Claims 1, 18, 19, and 21 have been amended.
Claims 1-22 are pending and under examination.
Rejections/Objections Withdrawn
The following rejections and objections are withdrawn in view of amendments to the claims filed 10/21/2025:
The objections to claims 18 and 19 for informalities.
The rejection of claims 21 and 22 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph.
Rejections Maintained
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 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 5, 12, 19, and 20 of U.S. Patent No. 11155629 in view of US20050053608A1, Weber et al, published March 10, 2005, US20130149299A1, Baughman et al, and US20170029512A1, Raum et al, published February 2, 2017.
The US Patent claims recite:
4. The method of claim 1, wherein said antibody construct comprises:
(a) a polypeptide comprising in the following order starting from the N-terminus:
(i) a polypeptide comprising the amino acid sequence of SEQ ID NO: 159;
(ii) a peptide linker comprising the amino acid sequence selected from any one of SEQ ID NOs: 1-9;
(iii) a polypeptide comprising the amino acid sequence selected from the group consisting of: SEQ ID NO: 19, SEQ ID NO: 28, SEQ ID NO: 37, SEQ ID NO: 46, SEQ ID NO: 55, SEQ ID NO: 64, SEQ ID NO: 73, SEQ ID NO: 82, SEQ ID NO: 91, SEQ ID NO: 100, and SEQ ID NO: 103; and
(iv) optionally, a His-tag comprising the amino acid sequence of SEQ ID NO: 10….
5. The method of claim 4, wherein said antibody construct comprises a polypeptide comprising the amino acid sequence of SEQ ID NO: 160.
12. A method for treating glioblastoma or glioma, comprising administering to a subject in need thereof an effective amount of a polypeptide comprising an amino acid sequence of SEQ ID NO: 160.
19. The method of claim 12, wherein said polypeptide is administered intravenously (IV).
20. The method of claim 12, wherein said polypeptide is administered by continuous intravenous (IV) administration.
Regarding instant claims 1 and 2, the US Patent claim 1 recites: “a method for treating glioblastoma or glioma, comprising administering to a subject in need thereof an effective amount of a bispecific antibody construct, said antibody construct comprises a first binding domain which binds to human and macaque epidermal growth factor receptor VIII (EGFRVIII) on the surface of a target cell and a second binding domain which binds to human CD3 on the surface of a T cell, wherein the first binding domain comprises a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 157, and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 158.” US Patent SEQ ID NO: 157 is identical to instantly claimed SEQ ID NO: 9 and US Patent SEQ ID NO: 158 is identical to instantly claimed SEQ ID NO: 10 (See sequence alignments below).
Regarding instant claims 1 and 3, US Patent claim 4 recites: “The method of claim 1, wherein said antibody construct comprises: (a) a polypeptide comprising in the following order starting from the N-terminus: (i) a polypeptide comprising the amino acid sequence of SEQ ID NO: 159; (ii) a peptide linker comprising the amino acid sequence selected from any one of SEQ ID NOs: 1-9; (iii) a polypeptide comprising the amino acid sequence selected from the group consisting of: SEQ ID NO: 19, SEQ ID NO: 28, SEQ ID NO: 37, SEQ ID NO: 46, SEQ ID NO: 55, SEQ ID NO: 64, SEQ ID NO: 73, SEQ ID NO: 82, SEQ ID NO: 91, SEQ ID NO: 100, and SEQ ID NO: 103; and (iv) optionally, a His-tag comprising the amino acid sequence of SEQ ID NO: 10….” The recited US Patent SEQ ID NO: 159 is identical to instantly claimed SEQ ID NO: 11 and the recited US Patent SEQ ID NO: 100 is identical to instantly claimed SEQ ID NO: 104. The recited US Patent SEQ ID NO: 98 is identical to the instantly claimed SEQ ID NO: 102 and the recited US Patent SEQ ID NO: 99 is identical to the instantly claimed SEQ ID NO: 103.
Regarding instant claim 4, the US Patent claim 5 recites: “The method of claim 4, wherein said antibody construct comprises a polypeptide comprising the amino acid sequence of SEQ ID NO: 160.” US Patent SEQ ID NO: 160 is identical to instant SEQ ID NO: 13.
Regarding instant claim 8, the US Patent claims 19 and 20 recite: 19. The method of claim 12, wherein said polypeptide is administered intravenously (IV). 20. The method of claim 12, wherein said polypeptide is administered by continuous intravenous (IV) administration.
The US Patent claims recite the method of treating glioblastoma, comprising administering to a subject in need thereof, an effective amount of a bispecific antibody construct, comprising the instantly claimed SEQ ID NOs. However, the US Patent does not recite the dosage or length of administration of the antibody, as required by claim 1 and claims 5-17. Weber and Baughman remedy these deficiencies.
Weber teaches a method of inhibiting cell proliferation associated with the expression of EGFRvIII, comprising treating cells expressing EGFRvIII with an effective amount of the EGFRvIII antibody or fragment, which can be performed in vivo, on humans suffering from a cancer [0026][0037][0053]. Weber also teaches the typical daily dosage ranges from about 0.001mg/kg to up to 100mg/kg or more [0243]. When calculated, this is equivalent to 70ug/day to 700,000ug/day for a 70kg adult. Weber also teaches that the dosage of the antibody formulation for a given patient will be determined by the attending physician taken into consideration various factors known to modify the action of drugs [0242].
Weber does not teach that the anti-EGFRvIII agent is administered for at least 14 days.
Baughman resolves this deficiency; Baughman teaches the initial dose of ant-EGFRvIII antibody is preferably administered over 2 weeks [0093].
It would have been prima facie obvious to a person of ordinary skill in the art at the time the invention was filed to treat EGFRvIII-positive cancer, the method comprising administering to a subject in need thereof an anti-EGFRvIII agent, at an initial dose of 15ug/day to 12000 ug/day, for at least 14 days, as taught by Weber and Baughman, wherein the anti-EGFRvIII agent comprises the amino acid sequences recited in US Patent No. 11155629.
One of ordinary skill in the art would have been motivated to, and have a reasonable expectation of success to, because: 1) Weber teaches administering an anti-EGFRvIII agent to treat cancer, specifically at a dose range which includes the instantly claimed dose and teaches the dosage is ultimately determined by the physician, 2) Baughman teaches safely administering an anti-EGFRvIII agent for at least 14 days, 3) the US Patent recites an anti-EGFRvIII agent comprising the instantly claimed SEQ ID NOs, and the use of this antibody construct for treatment of glioblastoma.
MPEP 2144.05 states: “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 the instant case, given the known function of the antibody in cancer treatment, and given the disclosures of each reference for arriving at therapeutic doses, it is well within the level of the ordinary skilled artisan to adjust the dosages and timing of administration for optimal therapeutic efficacy and safety, and to arrive at the dosages and timing of administration instantly claimed, and to expect successful therapeutic cancer treatment.
Regarding claims 5-7, the US Patent does not recite the daily dosage required by the instant claims. Weber teaches the typical daily dosage of the EGFRvIII antibody ranges from about 0.001mg/kg to up to 100mg/kg or more [00243]. When calculated, this is equivalent to 70ug/day to 700,000ug/day for a 70kg adult. Weber also teaches that the dosage of the antibody formulation for a given patient will be determined by the attending physician taken into consideration various factors known to modify the action of drugs [0242].
Regarding claims 9-11, the US Patent does not recite typical daily dosages of the antibody. Weber teaches the typical daily dosage of the EGFRvIII antibody ranges from about 0.001mg/kg to up to 100mg/kg or more [00243], the equivalent of about 70ug/day to 700,000ug/day for a 70kg adult.
Weber does not teach the anti-EGFRvIII agent is administered for at least 28 days. Baughman remedies this deficiency and teaches the efficacious target is reached by providing an initial dose of the anti-EGFRvIII antibody over 4 weeks [0013].
Regarding claims 12-15, the US Patent does not teach the method of treatment further comprises administering to the subject one or more subsequent doses of the anti-EGFRvIII agent, at the instantly claimed dose ranges for at least 14 days, or for at least 28 days. Baughman remedies this deficiency and teaches the initial dosage of anti-EGFR antibody should be followed by a subsequent dosage of equal or smaller amounts of antibody [0013]. Baughman teaches each subsequent dose is at least 0.01mg/kg but does not exceed 50mg/kg [0016], which is equivalent to at least 700ug/day to no more than 3,500,000ug/day for a 70kg adult.
Regarding claims 12-13, Baughman teaches the subsequent does of anti-EGFR antibody can be administered once per week, or once every 2 to 3 weeks [0020], indicating that the subsequent doses are administered for at least 14 days.
Regarding claims 14-15, Baughman teaches two or more subsequent doses of anti-EGFR antibody are administered and are preferably separated from each other by two weeks to about two months [0028], indicating that the subsequent doses are administered for at least 28 days.
Regarding claims 16 and 17, the US Patent claims do not recite that doses are administered at least a week after the previous dose or that the anti-EGFRvIII agent is administered at a 14-day on/14-day off cycle, or a 28-day on/14-day off cycle. Baughman remedies this deficiency.
Regarding claim 16, Baughman teaches an initial dose of the anti-EGFR antibody is administered, and is not followed by a subsequent maintenance dose for at least 1 week [0093].
Regarding claim 17, Baughman teaches the initial dose of anti-EGFR antibody is administered in 2 weeks and preferable subsequent doses are separated by 2 weeks [0093].
Regarding claims 18 and 19, Weber and Baughman both do not teach the method of treatment further comprises administering an anti-inflammatory agent. Raum remedies this deficiency and teaches that the anti-EGFRvIII agent composition could further comprise another biologically active drug agent, such as corticosteroids [0326].
Regarding claim 20, the US Patent does not teach the method of treatment further comprises obtaining a biological sample and detecting the presence of EGFRvIII or measuring the expression level of EGFRvIII in each sample. Weber teaches testing the expression levels of EGFRvIII on human tumors by staining frozen tissues sections from a variety of cancer patients. Weber teaches it may be advantageous to test patients before using therapeutic antibodies to ensure that the tumor which is being treated expresses EGFRvIII [0372][0374].
It would have been prima facie obvious to a person of ordinary skill in the art at the time the invention was filed to treat EGFRvIII-positive cancer specifically glioblastoma, the method comprising administering to a subject in need thereof an anti-EGFRvIII agent, at an initial dose of 15ug/day to 12000 ug/day, for at least 14 days or at least 28 days, as taught by Weber and Baughman, wherein the anti-EGFRvIII agent comprises the amino acid sequences instantly claimed and recited by the patented claims of US Patent No. 11155629, and further comprises subsequent doses at the range of dosages instantly claimed, and further comprising administering corticosteroid as taught by Raum.
One of ordinary skill in the art would have been motivated to, and have a reasonable expectation of success to, because: 1) Weber teaches administering an anti-EGFRvIII agent to treat cancer, specifically at a dose range which includes the instantly claimed dose and teaches the dosage is ultimately determined by the physician, 2) Baughman teaches safely administering an anti-EGFRvIII agent for at least 14 days, or at least 28 days, 3) the US Patent recites an anti-EGFRvIII agent comprising the instantly claimed SEQ ID NOs, and the use of this antibody construct for treatment of glioblastoma. One of ordinary skill in the art would have known to optimize the effective dose for the anti-EGFRvIII agent to treat glioblastoma, to administer for at least 2 weeks, or at least 4 weeks with an initial dose and subsequent doses, as Baughman demonstrates the antibody is safe to administer for that length of time, and to test for the presence of EGFRvIII in a patient sample.
Claims 21 and 22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 5, 12, 19, and 20 of U.S. Patent No. 11155629 in view of US20050053608A1, Weber et al, published March 10, 2005 and US20130149299A1, Baughman et al, and further in view of “Comparison of Biomarker Assays for EGFR: Implications for Precision Medicine in Patients with Glioblastoma, Lassman et al, published February 2019.
The combined references teach the method of treating EGFRvIII-positive cancer by administering an anti-EGFRvIII agent, the method further comprising obtaining a biological sample from the subject and detecting presence of EGFRvIII. The combined references do not teach assessing for EGFRvIII-positivity accordingly to H-score, wherein said H-score of a biological sample of the subject in need of treatment is from 8-280.
Lassman teaches using H-score as one of the markers for patient selection in patients with glioblastoma in order to improve therapy (Abstract). Lassman teaches IHC was done on 34 glioblastomas and H-score was calculated in the range of 0-300. Lassman teaches that the H-score for the patient samples ranged from 0-250 but that some samples which were classified as low EGFR expression by H-score, were classified as EGFR-amplified by FISH (Figure 5, Results).
It would have been prima facie obvious to a person of ordinary skill in the art at the time the invention was filed to treat EGFRvIII-positive cancer by administering the anti-EGFRvIII as the combined references teach and to assess the EGFRvIII-positivity accordingly to H-score wherein the H-score is from 8-280.
One of ordinary skill in the art would have been motivated to, and have a reasonable expectation of success given: 1) the combined references teach the method of treatment and Weber specifically teaches measuring the EGFRvIII expression levels in patient tumors could be advantageous for patient selection and could provide a therapeutic advantage, and 2) Lassman teaches using H-score to assess EGFRvIII expression and that the range of H-score in glioblastoma patients needing therapy ranges widely from 0-250.
US Patent No. 11155629 SEQ ID NO: 159 is identical to Instant SEQ ID NO: 11
US-16-676-170-159
Filing date in PALM: 2019-11-06
Sequence 159, US/16676170
Patent No. 11155629
GENERAL INFORMATION
APPLICANT: AMGEN RESEARCH (MUNICH) GMBH
TITLE OF INVENTION: BANTIBODY CONSTRUCTS FOR EGFRVIII AND CD3
FILE REFERENCE: 32243/49899B
CURRENT APPLICATION NUMBER: US/16/676,170
CURRENT FILING DATE: 2019-11-06
PRIOR APPLICATION NUMBER: US 15/225,627
PRIOR FILING DATE: 2016-08-01
PRIOR APPLICATION NUMBER: US 62/199,945
PRIOR FILING DATE: 2015-07-31
PRIOR APPLICATION NUMBER: US 62/290,861
PRIOR FILING DATE: 2016-02-03
NUMBER OF SEQ ID NOS: 196
SEQ ID NO 159
LENGTH: 251
TYPE: PRT
ORGANISM: Artificial Sequence
%
Result Query Filing
No. Score Match Length ID Date Dups Description
1 1342 100.0 251 US-15-225-627A-159 2016-08-01 7 ANTIBODY CONSTRUCTS FOR EGFRVIII AND CD3
ALIGNMENT:
Query Match 100.0%; Score 1342; Length 251;
Best Local Similarity 100.0%;
Matches 251; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVESGGGVVQSGRSLRLSCAASGFTFRNYGMHWVRQAPGKCLEWVAVIWYDGSDKYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVESGGGVVQSGRSLRLSCAASGFTFRNYGMHWVRQAPGKCLEWVAVIWYDGSDKYY 60
Qy 61 ADSVRGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGYDILTGNPRDFDYWGQGTLV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVRGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGYDILTGNPRDFDYWGQGTLV 120
Qy 121 TVSSGGGGSGGGGSGGGGSDTVMTQTPLSSHVTLGQPASISCRSSQSLVHSDGNTYLSWL 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 TVSSGGGGSGGGGSGGGGSDTVMTQTPLSSHVTLGQPASISCRSSQSLVHSDGNTYLSWL 180
Qy 181 QQRPGQPPRLLIYRISRRFSGVPDRFSGSGAGTDFTLEISRVEAEDVGVYYCMQSTHVPR 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 QQRPGQPPRLLIYRISRRFSGVPDRFSGSGAGTDFTLEISRVEAEDVGVYYCMQSTHVPR 240
Qy 241 TFGCGTKVEIK 251
|||||||||||
Db 241 TFGCGTKVEIK 251
US Patent No. 11155629 SEQ ID NO: 158 is identical to Instant SEQ ID NO:10
%
Result Query Filing
No. Score Match Length ID Date Dups Description
1 589 100.0 112 US-15-225-627A-158 2016-08-01 7 ANTIBODY CONSTRUCTS FOR EGFRVIII AND CD3
ALIGNMENT:
Query Match 100.0%; Score 589; Length 112;
Best Local Similarity 100.0%;
Matches 112; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DTVMTQTPLSSHVTLGQPASISCRSSQSLVHSDGNTYLSWLQQRPGQPPRLLIYRISRRF 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DTVMTQTPLSSHVTLGQPASISCRSSQSLVHSDGNTYLSWLQQRPGQPPRLLIYRISRRF 60
Qy 61 SGVPDRFSGSGAGTDFTLEISRVEAEDVGVYYCMQSTHVPRTFGCGTKVEIK 112
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SGVPDRFSGSGAGTDFTLEISRVEAEDVGVYYCMQSTHVPRTFGCGTKVEIK 112
US-16-676-170-158
Filing date in PALM: 2019-11-06
Sequence 158, US/16676170
Patent No. 11155629
GENERAL INFORMATION
APPLICANT: AMGEN RESEARCH (MUNICH) GMBH
TITLE OF INVENTION: BANTIBODY CONSTRUCTS FOR EGFRVIII AND CD3
FILE REFERENCE: 32243/49899B
CURRENT APPLICATION NUMBER: US/16/676,170
CURRENT FILING DATE: 2019-11-06
PRIOR APPLICATION NUMBER: US 15/225,627
PRIOR FILING DATE: 2016-08-01
PRIOR APPLICATION NUMBER: US 62/199,945
PRIOR FILING DATE: 2015-07-31
PRIOR APPLICATION NUMBER: US 62/290,861
PRIOR FILING DATE: 2016-02-03
NUMBER OF SEQ ID NOS: 196
SEQ ID NO 158
LENGTH: 112
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic peptide
US Patent No. 11155629 SEQ ID NO: 157 is identical to Instant SEQ ID NO: 9
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
1 669 100.0 124 US-15-225-627A-157 2016-08-01 7 ANTIBODY CONSTRUCTS FOR EGFRVIII AND CD3
ALIGNMENT:
Query Match 100.0%; Score 669; Length 124;
Best Local Similarity 100.0%;
Matches 124; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVESGGGVVQSGRSLRLSCAASGFTFRNYGMHWVRQAPGKCLEWVAVIWYDGSDKYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVESGGGVVQSGRSLRLSCAASGFTFRNYGMHWVRQAPGKCLEWVAVIWYDGSDKYY 60
Qy 61 ADSVRGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGYDILTGNPRDFDYWGQGTLV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVRGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGYDILTGNPRDFDYWGQGTLV 120
Qy 121 TVSS 124
||||
Db 121 TVSS 124
US-16-676-170-157
Filing date in PALM: 2019-11-06
Sequence 157, US/16676170
Patent No. 11155629
GENERAL INFORMATION
APPLICANT: AMGEN RESEARCH (MUNICH) GMBH
TITLE OF INVENTION: BANTIBODY CONSTRUCTS FOR EGFRVIII AND CD3
FILE REFERENCE: 32243/49899B
CURRENT APPLICATION NUMBER: US/16/676,170
CURRENT FILING DATE: 2019-11-06
PRIOR APPLICATION NUMBER: US 15/225,627
PRIOR FILING DATE: 2016-08-01
PRIOR APPLICATION NUMBER: US 62/199,945
PRIOR FILING DATE: 2015-07-31
PRIOR APPLICATION NUMBER: US 62/290,861
PRIOR FILING DATE: 2016-02-03
NUMBER OF SEQ ID NOS: 196
SEQ ID NO 157
LENGTH: 124
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic peptide
US Patent No. 11155629 SEQ ID NO: 98 is identical to Instant SEQ ID NO: 102
US-16-676-170-98
Filing date in PALM: 2019-11-06
Sequence 98, US/16676170
Patent No. 11155629
GENERAL INFORMATION
APPLICANT: AMGEN RESEARCH (MUNICH) GMBH
TITLE OF INVENTION: BANTIBODY CONSTRUCTS FOR EGFRVIII AND CD3
FILE REFERENCE: 32243/49899B
CURRENT APPLICATION NUMBER: US/16/676,170
CURRENT FILING DATE: 2019-11-06
PRIOR APPLICATION NUMBER: US 15/225,627
PRIOR FILING DATE: 2016-08-01
PRIOR APPLICATION NUMBER: US 62/199,945
PRIOR FILING DATE: 2015-07-31
PRIOR APPLICATION NUMBER: US 62/290,861
PRIOR FILING DATE: 2016-02-03
NUMBER OF SEQ ID NOS: 196
SEQ ID NO 98
LENGTH: 125
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic peptide
%
Result Query Filing
No. Score Match Length ID Date Dups Description
1 673 100.0 125 US-13-122-271A-177 2011-07-14 85 Bispecific single chain antibodies with specificity for high molecular weight ta
ALIGNMENT:
Query Match 100.0%; Score 673; Length 125;
Best Local Similarity 100.0%;
Matches 125; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYAT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYAT 60
Qy 61 YYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTL 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 YYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTL 120
Qy 121 VTVSS 125
|||||
Db 121 VTVSS 125
US Patent No. 11155629 SEQ ID NO: 99 is identical to Instant SEQ ID NO.103
US-16-676-170-99
Filing date in PALM: 2019-11-06
Sequence 99, US/16676170
Patent No. 11155629
GENERAL INFORMATION
APPLICANT: AMGEN RESEARCH (MUNICH) GMBH
TITLE OF INVENTION: BANTIBODY CONSTRUCTS FOR EGFRVIII AND CD3
FILE REFERENCE: 32243/49899B
CURRENT APPLICATION NUMBER: US/16/676,170
CURRENT FILING DATE: 2019-11-06
PRIOR APPLICATION NUMBER: US 15/225,627
PRIOR FILING DATE: 2016-08-01
PRIOR APPLICATION NUMBER: US 62/199,945
PRIOR FILING DATE: 2015-07-31
PRIOR APPLICATION NUMBER: US 62/290,861
PRIOR FILING DATE: 2016-02-03
NUMBER OF SEQ ID NOS: 196
SEQ ID NO 99
LENGTH: 109
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic peptide
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
1 581 100.0 109 US-13-122-271A-161 2011-07-14 101 Bispecific single chain antibodies with specificity for high molecular weight ta
ALIGNMENT:
Query Match 100.0%; Score 581; Length 109;
Best Local Similarity 100.0%;
Matches 109; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGT 60
Qy 61 PARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 109
|||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVFGGGTKLTVL 109
US Patent No. 11155629 SEQ ID NO: 100 is identical to Instant SEQ ID NO:104
US-16-676-170-100
Filing date in PALM: 2019-11-06
Sequence 100, US/16676170
Patent No. 11155629
GENERAL INFORMATION
APPLICANT: AMGEN RESEARCH (MUNICH) GMBH
TITLE OF INVENTION: BANTIBODY CONSTRUCTS FOR EGFRVIII AND CD3
FILE REFERENCE: 32243/49899B
CURRENT APPLICATION NUMBER: US/16/676,170
CURRENT FILING DATE: 2019-11-06
PRIOR APPLICATION NUMBER: US 15/225,627
PRIOR FILING DATE: 2016-08-01
PRIOR APPLICATION NUMBER: US 62/199,945
PRIOR FILING DATE: 2015-07-31
PRIOR APPLICATION NUMBER: US 62/290,861
PRIOR FILING DATE: 2016-02-03
NUMBER OF SEQ ID NOS: 196
SEQ ID NO 100
LENGTH: 249
TYPE: PRT
ORGANISM: Artificial Sequence
%
Result Query Filing
No. Score Match Length ID Date Dups Description
1 1338 100.0 249 US-13-122-271A-185 2011-07-14 44
ALIGNMENT:
Query Match 100.0%; Score 1338; Length 249;
Best Local Similarity 100.0%;
Matches 249; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYAT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYAT 60
Qy 61 YYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTL 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 YYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTL 120
Qy 121 VTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQ 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCGSSTGAVTSGNYPNWVQQ 180
Qy 181 KPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVF 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 KPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPEDEAEYYCVLWYSNRWVF 240
Qy 241 GGGTKLTVL 249
|||||||||
Db 241 GGGTKLTVL 249
US Patent No. 11155629 SEQ ID NO: 160 is identical to instant SEQ ID NO 13
US-16-676-170-160
Filing date in PALM: 2019-11-06
Sequence 160, US/16676170
Patent No. 11155629
GENERAL INFORMATION
APPLICANT: AMGEN RESEARCH (MUNICH) GMBH
TITLE OF INVENTION: BANTIBODY CONSTRUCTS FOR EGFRVIII AND CD3
FILE REFERENCE: 32243/49899B
CURRENT APPLICATION NUMBER: US/16/676,170
CURRENT FILING DATE: 2019-11-06
PRIOR APPLICATION NUMBER: US 15/225,627
PRIOR FILING DATE: 2016-08-01
PRIOR APPLICATION NUMBER: US 62/199,945
PRIOR FILING DATE: 2015-07-31
PRIOR APPLICATION NUMBER: US 62/290,861
PRIOR FILING DATE: 2016-02-03
NUMBER OF SEQ ID NOS: 196
SEQ ID NO 160
LENGTH: 506
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic peptide
%
Result Query Filing
No. Score Match Length ID Date Dups Description
-------------------------------------------------------------------------------------------------------------
1 2712 98.3 506 US-15-225-627A-160 2016-08-01 8 ANTIBODY CONSTRUCTS FOR EGFRVIII AND CD3
ALIGNMENT:
Query Match 98.3%; Score 2712; Length 506;
Best Local Similarity 100.0%;
Matches 506; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVESGGGVVQSGRSLRLSCAASGFTFRNYGMHWVRQAPGKCLEWVAVIWYDGSDKYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVESGGGVVQSGRSLRLSCAASGFTFRNYGMHWVRQAPGKCLEWVAVIWYDGSDKYY 60
Qy 61 ADSVRGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGYDILTGNPRDFDYWGQGTLV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVRGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDGYDILTGNPRDFDYWGQGTLV 120
Qy 121 TVSSGGGGSGGGGSGGGGSDTVMTQTPLSSHVTLGQPASISCRSSQSLVHSDGNTYLSWL 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 TVSSGGGGSGGGGSGGGGSDTVMTQTPLSSHVTLGQPASISCRSSQSLVHSDGNTYLSWL 180
Qy 181 QQRPGQPPRLLIYRISRRFSGVPDRFSGSGAGTDFTLEISRVEAEDVGVYYCMQSTHVPR 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 QQRPGQPPRLLIYRISRRFSGVPDRFSGSGAGTDFTLEISRVEAEDVGVYYCMQSTHVPR 240
Qy 241 TFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGK 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TFGCGTKVEIKSGGGGSEVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGK 300
Qy 301 GLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGN 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 GLEWVARIRSKYNNYATYYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGN 360
Qy 361 FGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCG 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 FGNSYISYWAYWGQGTLVTVSSGGGGSGGGGSGGGGSQTVVTQEPSLTVSPGGTVTLTCG 420
Qy 421 SSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPE 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 SSTGAVTSGNYPNWVQQKPGQAPRGLIGGTKFLAPGTPARFSGSLLGGKAALTLSGVQPE 480
Qy 481 DEAEYYCVLWYSNRWVFGGGTKLTVL 506
||||||||||||||||||||||||||
Db 481 DEAEYYCVLWYSNRWVFGGGTKLTVL 506
Response to Applicant’s Arguments
The applicant argues none of the modifying art addresses the specific challenge of large biological molecules’ ability to penetrate the BBB. (Remarks, Pg. 9)
The ability for the claimed therapeutic to penetrate the BBB is enables in the art, as described in the 35 U.S.C. 103 rejection below.
New Rejections Necessitated by Amendment
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.
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.
Claims 1-20 are rejected under 35 U.S.C. 103 as being unpatentable over US20050053608A1, Weber et al, published March 10, 2005, in view of US20130149299A1, Razpotnik et al (Front Immunol. 2017 Sep 25;8:1181), Baughman et al, published June 13, 2013, US20170029512A1, and Raum et al, published February 2, 2017.
Regarding claim 1, Weber teaches a method of inhibiting cell proliferation associated with the expression of EGFRvIII, comprising treating cells expressing EGFRvIII with an effective amount of the EGFRvIII antibody or fragment, which can be performed in vivo, on humans suffering from a cancer [0026][0037][0053]. Weber also teaches the typical daily dosage ranges from about 0.001mg/kg to up to 100mg/kg or more [0243]. When calculated, this is equivalent to 70ug/day to 700,000ug/day for a 70kg adult. Weber also teaches that the dosage of the antibody formulation for a given patient will be determined by the attending physician taken into consideration various factors known to modify the action of drugs [0242]. Weber teaches intravenous and subcutaneous administration of the antibody formulation ([0233], Lines 1-4).
Regarding claim 2, Weber teaches the cancer treated with an anti-EGFRvIII can be glioblastoma [0037][0053]. Raum also teaches the cancer treated with the disclosed antibody can include glioblastoma [0356].
Regarding claims 5-7, Weber teaches the typical daily dosage of the EGFRvIII antibody ranges from about 0.001mg/kg to up to 100mg/kg or more [00243]. When calculated, this is equivalent to 70ug/day to 700,000ug/day for a 70kg adult. Weber also teaches that the dosage of the antibody formulation for a given patient will be determined by the attending physician taken into consideration various factors known to modify the action of drugs [0242].
Regarding claim 8, Weber teaches the preferred route of administration for the antibody is continuous infusion [0235].
Regarding claims 9-11, Weber teaches the typical daily dosage of the EGFRvIII antibody ranges from about 0.001mg/kg to up to 100mg/kg or more [00243], the equivalent of about 70ug/day to 700,000ug/day for a 70kg adult.
Regarding claim 20, Weber teaches testing the expression levels of EGFRvIII on human tumors by staining frozen tissues sections from a variety of cancer patients. Weber teaches it may be advantageous to test patients before using therapeutic antibodies to ensure that the tumor which is being treated expresses EGFRvIII [0372][0374].
Weber does not teach (1) the EGFRvIII-positive cancer is brain cancer, (2) the anti-EGFRvIII agent is administered for at least 14 days or at least 28 days, (3) the anti-EGFRvIII agent comprises the amino acid sequences instantly claimed, (4) the method of treatment further comprises administering to the subject one or more subsequent doses of the anti-EGFRvIII agent, at the instantly claimed dose ranges for at least 14 days, or for at least 28 days (5) subsequent doses are administered at least a week after the previous dose or that the anti-EGFRvIII agent is administered at a 14-day on/14-day off cycle, or a 28-day on/14-day off cycle (6) the method of treatment further comprises administering an anti-inflammatory agent.
These deficiencies are taught by Razpotnik, Baughman, and Raum.
Razpotnik:
Regarding the limitation of claim 1 wherein the anti-EGFRvIII agent is administered intravenously or subcutaneously and used to treat brain cancer, Razpotnik teaches successful treatment in a glioblastoma xenograft model with systemic administration of a BiTE that targets CD3 and EGFRvIII. Treatment prolonged survival in mice, and in high doses resulted in complete remission without toxicity. The mechanism by which the antibody crossed the BBB was unknown, but it was believed enhanced passage was due to the reduced size of the BiTEs compared with conventional antibodies. (Pg. 5, Left column, paragraph 1).
Baughman:
Regarding the limitation of claim 1 wherein the anti-EGFR agent is administered for at least 14 days, Baughman teaches the initial dose of ant-EGFR antibody is preferably administered over 2 weeks [0093].
Regarding the limitation of claims 9-15 wherein the anti-EGFR is administered for at least 28 days. Baughman remedies this deficiency and teaches the efficacious target is reached by providing an initial dose of the anti-EGFR antibody over 4 weeks [0013].
Regarding the limitation of claims 12-15 wherein the method of treatment further comprises administering to the subject one or more subsequent doses of the anti-EGFR agent, at the instantly claimed dose ranges for at least 14 days, or for at least 28 days. Baughman teaches the initial dosage of anti-EGFR antibody should be followed by a subsequent dosage of equal or smaller amounts of antibody [0013]. Baughman teaches each subsequent dose is at least 0.01mg/kg but does not exceed 50mg/kg [0016], which is equivalent to at least 700ug/day to no more than 3,500,000ug/day for a 70kg adult.
Regarding claims 12-13, Baughman teaches the subsequent does of anti-EGFR antibody can be administered once per week, or once every 2 to 3 weeks [0020], indicating that the subsequent doses are administered for at least 14 days.
Regarding claims 14-15, Baughman teaches two or more subsequent doses of anti-EGFR antibody are administered and are preferably separated from each other by two weeks to about two months [0028], indicating that the subsequent doses are administered for at least 28 days.
Regarding claims 16 and 17, wherein the subsequent doses are administered at least a week after the previous dose or that the anti-EGFR agent is administered at a 14-day on/14-day off cycle, or a 28-day on/14-day off cycle, Baughman teaches an initial dose of the anti-EGFR antibody is administered, and is not followed by a subsequent maintenance dose for at least 1 week [0093]. Baughman teaches the initial dose of anti-EGFR antibody is administered in 2 weeks and preferable subsequent doses are separated by 2 weeks [0093].
Raum:
Regarding the amino acid sequences of claim 1, Raum teaches a bispecific antibody construct comprising a first binding domain which binds to EGFRvIII and a second binding domain which binds to CD3. Raum teaches the antibody comprises SEQ ID NOs: 157, 158, 26 and 90 (Reference claims 1 and 4). Reference SEQ ID NOs: 157, 158, 26, and 90 are 100% identical to instantly claimed SEQ ID NOs 9, 10, 102, and 103 respectively (See sequence alignments below). Raum also teaches this antibody can be useful as a pharmaceutical composition for the treatment of cancer [0351]. Raum also teaches the antibody can be administered at an effective dose ranging from about 0.1ug/kg to about 30mg/kg [0371].
Regarding claim 3, Raum teaches the anti-EGFRvIII agent comprises the amino acid sequence of SEQ ID NO: 159. Reference SEQ ID NO: 159 is 100% identical to instantly claimed SEQ ID NO: 11. Raum also teaches the anti-EGFRvIII agent comprises the amino acid sequence of SEQ ID NO: 100 (Claim 4). Reference SEQ ID NO: 100 is 100% identical to instantly claimed SEQ ID NO: 104. See sequence alignments below.
Regarding claim 4, Raum teaches the anti-EGFRvIII agent comprises the amino acid sequence SEQ ID NO: 160 which is 100% identical to instantly claimed SEQ ID NO: 12, 13 (Claim 5). See sequence alignments below.
Regarding claims 18 and 19, regarding method of treatment further comprises administering an anti-inflammatory agent. Raum remedies this deficiency and teaches that the anti-EGFRvIII agent composition could further comprise another biologically active drug agent, such as corticosteroids [0326].
It would have been obvious to one having ordinary skill in the art to modify the methods of Weber with the teachings of Razpotnik, Baughman and Raum, wherein (1) the EGFRvIII-positive cancer is brain cancer, (2) the anti-EGFRvIII agent is administered for at least 14 days or at least 28 days, (3) the anti-EGFRvIII agent comprises the amino acid sequences instantly claimed, (4) the method of treatment further comprises administering to the subject one or more subsequent doses of the anti-EGFRvIII agent, at the instantly claimed dose ranges for at least 14 days, or for at least 28 days (5) subsequent doses are administered at least a week after the previous dose or that the anti-EGFRvIII agent is administered at a 14-day on/14-day off cycle, or a 28-day on/14-day off cycle (6) the method of treatment further comprises administering an anti-inflammatory agent.
One of ordinary skill in the art would have been motivated to, and have a reasonable expectation of success to, because: (1) Weber teaches administering an anti-EGFRvIII agent to treat cancer, specifically at a dose range which includes the instantly claimed dose and teaches the dosage is ultimately determined by the physician, (2) Razpotink teaches anti-EGFR/anti-CD3 agents administered systemically can pass through the BBB and treat glioblastoma, (3) Baughman teaches safely administering an anti-EGFR agent for at least 14 days, (4) Raum teaches an anti-EGFRvIII agent comprising the instantly claimed SEQ ID NOs, and the use of this antibody construct for treatment of cancer.
MPEP 2144.05 states: “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 the instant case, given the known function of the antibody in cancer treatment, and given the disclosures of each reference for arriving at therapeutic doses, it is well within the level of the ordinary skilled artisan to adjust the dosages and timing of administration for optimal therapeutic efficacy and safety, and to arrive at the dosages and timing of administration instantly claimed, and to expect successful therapeutic cancer treatment.
Claims 21 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over US20050053608A1, Weber et al, published March 10, 2005, in view of US20130149299A1, Razpotnik et al (Front Immunol. 2017 Sep 25;8:1181), Baughman et al, published June 13, 2013 and US20170029512A1, Raum et al, as applied to claims 1-20 above, and further in view of “Comparison of Biomarker Assays for EGFR: Implications for Precision Medicine in Patients with Glioblastoma, Lassman et al, published February 2019.
The teachings of Weber, Razpotnik, Baughman, and Raum are set forth above. Weber teaches teaches testing the expression levels of EGFRvIII on human tumors by staining frozen tissues sections from a variety of cancer patients.
The combined references teach the method of treating EGFRvIII-positive brain cancer by administering an anti-EGFRvIII agent, the method further comprising obtaining a biological sample from the subject and detecting presence of EGFRvIII. The combined references do not teach assessing for EGFRvIII-positivity accordingly to H-score, wherein said H-score of a biological sample of the subject in need of treatment is from 8-280.
Lassman teaches using H-score as one of the markers for patient selection in patients with glioblastoma in order to improve therapy (Abstract). Lassman teaches IHC was done on 34 glioblastomas and H-score was calculated in the range of 0-300. Lassman teaches that the H-score for the patient samples ranged from 0-250 but that some samples which were classified as low EGFR expression by H-score, were classified as EGFR-amplified by FISH (Figure 5, Results).
It would have been prima facie obvious to a person of ordinary skill in the art at the time the invention was filed to treat EGFRvIII-positive cancer by administering the anti-EGFRvIII as the combined references teach and to assess the EGFRvIII-positivity accordingly to H-score wherein the H-score is from 8-280.
One of ordinary skill in the art would have been motivated to, and have a reasonable expectation of success given: 1) the combined references teach the method of treatment and Weber specifically teaches measuring the EGFRvIII expression levels in patient tumors could be advantageous for patient selection and could provide a therapeutic advantage, and 2) Lassman teaches using H-score to assess EGFRvIII expression and that the range of H-score in glioblastoma patients needing therapy ranges widely from 0-250.
Reference SEQ ID NO: 26 is 100% identical to instantly claimed SEQ ID NO: 102
BDN58969
ID BDN58969 standard; protein; 125 AA.
AC BDN58969;
DT 23-MAR-2017 (first entry)
DE Anti-CD3-EGFR VIII bispecific antibody VH, SEQ ID 26.
KW respiratory-gen.; therapeutic; uropathic.
OS Unidentified.
CC PN US2017029512-A1.
CC PD 02-FEB-2017.
CC PF 01-AUG-2016; 2016US-00225627.
PR 31-JUL-2015; 2015US-0199945P.
PR 03-FEB-2016; 2016US-0290861P.
CC PA (AMGE-) AMGEN RES MUNICH.
CC PI Herrmann I, Hoffmann P, Kufer P, Muenz M, Rau D, Raum T;
DR WPI; 2017-09047T/15.
CC PS Claim 4; SEQ ID NO 26; 190pp; English.
%
Result Query Filing
No. Score Match Length ID Date Dups Description
1 673 100.0 125 ATS08592 -- 290 CD3 epsilon epitope binding VH region SEQ:33.
ALIGNMENT:
Query Match 100.0%; Score 673; Length 125;
Best Local Similarity 100.0%;
Matches 125; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYAT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLKLSCAASGFTFNKYAMNWVRQAPGKGLEWVARIRSKYNNYAT 60
Qy 61 YYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTL 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 YYADSVKDRFTISRDDSKNTAYLQMNNLKTEDTAVYYCVRHGNFGNSYISYWAYWGQGTL 120
Qy 121 VTVSS 125
|||||
Db 121 VTVSS 125
Reference SEQ ID NO: 90 is 100% identical to instantly claimed SEQ ID NO: 103
%
Result Query Filing
No. Score Match Length ID Date Du