DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2 Applicant's amendment, filed on 06/19/2024, is acknowledged.
3. Claims 1-3, 6, 8, 10-12, 14, 16, 19-22, 24, 27, 29, 33-34 and 37 are pending.
4. Applicant’s IDS, filed 03/21/2024 and 05/22/2026, is acknowledged.
5. The following is a quotation of 35 U.S.C. 112(b) (Pre AIA , 35 U.S.C. 112, second paragraph):
(B) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
6. Claims 33 and 37 are rejected under 35 U.S.C. 112(b), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
(a) the recitation “a method for making an ADC of claim 1” in claim 33 is ambiguous because the method step of culturing a host cell comprising a polynucleotide encoding the antibody and expressing the polynucleotide does not result in making an ADC.
(b) The recitation “an ADC that is the product of claim 33” in Claim 37 is indefinite because the outcome of the method steps in base claim 33 would result in in making anti-EGFRvIII antibody but not the ADC. Culturing a host cell encoding the antibody would not result in the claimed ADC.
7. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
8. Claim 33 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 11608380.
The `380 patent provides recombinant expression vectors capable of expressing a polypeptide comprising a heavy or light chain variable region of an anti-EGFRvIII antibody (See, H1H1863N2, SEQ ID NOs: 34 and 42 which comprise the claimed sequences) (see issued claims). For example, the present invention includes recombinant expression vectors comprising any of the nucleic acid molecules mentioned above, i.e., nucleic acid molecules encoding any of the HCVR, LCVR, and/or CDR sequences as set forth in Table 1. Also included within the scope of the present invention are host cells into which such vectors have been introduced, as well as methods of producing the antibodies or portions thereof by culturing the host cells under conditions permitting production of the antibodies or antibody fragments, and recovering the antibodies and antibody fragments so produced (see col., 6, lines 10+ and issued claims 1-11).
The `380 patent teaches a first ADC was produced by conjugating H1H1863N2 to the maytansinoid toxin DM1 via a non-cleavable MCC linker to produce “H1H1863N2-MCC-DM1.” A second ADC was produced by conjugating H1H1863N2 to a modified version of DM1 attached to a novel cleavable linker, referred to as “M0026” (also known as “compound 7” in WO2014/145090, the disclosure of which is incorporated by reference herein in its entirety), to yield “H1H1863N2-M0026.” (example 12).
Alignment of claimed SEQ ID NO: 10 with issued SEQ ID NO: 42.
Qy 1 DIQLTQSPSFLSASVGDRVTITCWASQGINNYLAWYQQKPGKAPKLLIYAASTLQTGVPS 60
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Db 1 DIQLTQSPSFLSASVGDRVTITCWASQGINNYLAWYQQKPGKAPKLLIYAASTLQTGVPS 60
Qy 61 RFSGSGSGTEFTLTISSLQPEDFATYYCQQLNSYPLTFGGGTKVEIK 107
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Db 61 RFSGSGSGTEFTLTISSLQPEDFATYYCQQLNSYPLTFGGGTKVEIK 107
Alignment of claimed SEQ ID NO: 2 with issued SEQ ID NO: 34.
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFPFSSYDMHWVRQATGKGLEWVSAIGTAGATYYP 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFPFSSYDMHWVRQATGKGLEWVSAIGTAGATYYP 60
Qy 61 GSVKGRFTISRENAKNSLYLQMNSLRAGDTAVYYCARGDYVWGTYRPLFDYWGQGTLVTV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GSVKGRFTISRENAKNSLYLQMNSLRAGDTAVYYCARGDYVWGTYRPLFDYWGQGTLVTV 120
Qy 121 SS 122
||
Db 121 SS 122
The reference teachings anticipate the claimed invention.
9. 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.
10. Claims 1-3, 6, 8, 10-12, 14, 20-22, 24, 27, 29 and 37 are rejected under 35 U.S.C. 103 as being unpatentable over WO/2014/145090 in view of Hartley et al (Nature, (2018) 8:10479).
The WO `090 publication teaches antibody-drug conjugates (ADC) was produced by conjugating H1H1863N2 (fully antibody having human Fc derived from IgG1 (i.e., H1)) to the maytansinoid DM1 via a non-cleavable MCC linker to produce "H1H1863N2-MCC-DM1." A second ADC was produced by conjugating H1H1863N2 to 7 to yield "H1H1863N2-7." When tested for cytotoxicity in vitro against MMT/EGFRvlII cells using the assay format described in Example 14, H1H1863N2-MCC-DM1 exhibited an IC50 of 12 nM whereas H1H1863N2-7 exhibited an IC50 of only 0.8 nM. Thus, in vitro, the anti-EGFRvIII ADC H1H1863N2-7 exhibited much more potent tumor cell killing ability than the corresponding antibody conjugated to DM1 via an MCC linker [00250] See Table 3.
The WO `090 publication shows the cell viability results of HEK293/hEGFRvIII cells (HEK293 cells expressing exogenous hEGFRvIII) treated with compound 6, isotype control antibody conjugated to compound 7 ("isotype Control-711), anti-EGFRvIII antibody conjugated to compound 7 ("EGFRvIII-7"), and unconjugated anti-EGFRvIII antibody ("EGFRvIII"), Figure 4 [0025]. In HEK293/hEGFRvIII cells, expressing hEGFRvIII at 360 fold above isotype control binding, the maytansinoid conjugate EGFRvIII-7 possesses an IC50 value of 0.4 nM (Figure 4). The naked EGFRvIII antibody was devoid of any anti-proliferation activity.
Figure 5 shows the cell viability results of MMT/hEGFRvIII cells (MMT cells expressing exogenous hEGFRvIII) treated with compound 6, isotype control antibody conjugated to compound 7 ("Isotype Control-7"), anti-EGFRvIII antibody conjugated to compound 7 ("EGFRvIII-7"), and unconjugated anti-EGFRvIII antibody ("EGFRvIII") [0026]. In MMT/hEGFRvIII cells, expressing hEGFRvIII at 280 fold above isotype control binding, the maytansinoid conjugate EGFRvIII-7 possesses an IC50 value of 0.3 nM (Figure 5). The naked EGFRvIII antibody was devoid of any anti-proliferation activity [00242].
Figure 6 shows the cell viability results of U251 /hEGFRvIII cells (U251 cells expressing exogenous hEGFRvIII) treated with compound 6, isotype control antibody conjugated to compound 7 ("fsotype Control-7"), anti-EGFRvIII antibody conjugated to compound 7 ("EGFRvIII-7"), and unconjugated anti-EGFRvIII antibody ("EGFRvIII"). In U251/hEGFRvIII cells (glioblastoma cancer line), expressing hEGFRvIII at 165 fold above isotype control binding, the maytansinoid conjugate EGFRvIII-7 possesses an IC50 value of 0.3 nM (Figure 6). The naked EGFRvIII antibody was devoid of any anti-proliferation activity [00243].
The greatest tumor inhibition was observed in mice dosed with 5 mg/kg H1H1863N2-7, where regression of the initial tumor was observed. The tumor growth inhibition of 102% resulting from treatment with 5 mg/kg H1H1863N2-7 was significantly greater relative to that observed following treatment of tumor with 5 mg/kg H1H1862N2-MCC-DM1 (83%). The superiority of the tumor growth inhibition induced by H1H1863N2-7 compared to H1H1863N2-MCC-DM1 was maintained at the 1 mg/kg dose as well. No anti-tumor effect was observed in groups treated with Control ADC using MCC- DM1 or 7 [00253].
Finally, the `090 publication teaches that Biologically Active Molecules that can be used in the context of the present invention include pyrrolobenzodiazapines (PDBs) [0055].
Alignment of claimed SEQ ID NO: 2, 12-14-16 with Anti-EGFRvIII antibody H1H1863N2 heavy chain variable region, SEQ 1.
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFPFSSYDMHWVRQATGKGLEWVSAIGTAGATYYP 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFPFSSYDMHWVRQATGKGLEWVSAIGTAGATYYP 60
Qy 61 GSVKGRFTISRENAKNSLYLQMNSLRAGDTAVYYCARGDYVWGTYRPLFDYWGQGTLVTV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GSVKGRFTISRENAKNSLYLQMNSLRAGDTAVYYCARGDYVWGTYRPLFDYWGQGTLVTV 120
Qy 121 SS 122
||
Db 121 SS 122
Alignment of claimed SEQ ID NO: 10, 12-14-16 with anti-EGFRvIII antibody H1H1863N2 light chain variable region, SEQ ID 5.
Qy 1 DIQLTQSPSFLSASVGDRVTITCWASQGINNYLAWYQQKPGKAPKLLIYAASTLQTGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQLTQSPSFLSASVGDRVTITCWASQGINNYLAWYQQKPGKAPKLLIYAASTLQTGVPS 60
Qy 61 RFSGSGSGTEFTLTISSLQPEDFATYYCQQLNSYPLTFGGGTKVEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTEFTLTISSLQPEDFATYYCQQLNSYPLTFGGGTKVEIK 107
The `090 publication teaches The term "human antibody" as used herein is intended to include antibodies having variable and constant regions derived from human immunoglobulin sequences (i.e., full antibody) [0044].
[00125] Administration of a therapeutically effective amount of a pharmaceutical composition described herein may be effected in different ways, e.g., by intravenous, intraperitoneal, subcutaneous, intramuscular, topical, intradermal, intranasal, or intrabronchial administration.
The disclosure provides methods, wherein additional therapy is radiation therapy, chemotherapy, or a combination of both [00135], [0002].
The reference teachings differ from the claimed invention only in the recitation of that the antibody is conjugated to tesirine in claims 1, 19, and 34.
Hartley et al teach pre-clinical pharmacology and mechanism of action of SG3199 (aka tesirine), the pyrrolobenzodiazepine (PBD) dimer warhead component of antibody-drug conjugate (ADC) payload tesirine. Synthetic pyrrolobenzodiazepine (PBD) dimers, where two PBD monomers are linked through their aromatic A-ring phenolic C8-positions via a flexible propyldioxy tether, are highly efficient DNA minor groove cross-linking agents with potent cytotoxicity. PBD dimer SG3199 is the released warhead component of the antibody-drug conjugate (ADC) payload tesirine (SG3249), currently being evaluated in several ADC clinical trials. SG3199 was potently cytotoxic against a panel of human solid tumour and haematological cancer cell lines with a mean GI50 of 151.5 pM. Following intravenous (iv) administration to rats SG3199 showed a very rapid clearance with a half life as short as 8 minutes. These combined properties of cytotoxic potency, rapid formation and persistence of DNA interstrand cross-links and very short half-life contribute to the emerging success of SG3199 as a warhead in clinical stage ADCs (abstract).
Hartley et al teach a PBD dimer which is the released warhead component of the antibody-drug conjugate (ADC) payload tesirine (SG3249 Fig. 1A). is the released warhead component of the antibody-drug conjugate (ADC) payload tesirine (SG3249 Fig. 1A18). Rovalpituzumab tesirine (Rova-T) has completed a phase I clinical trial for the treatment of small cell lung can cer19 and several other ADCs incorporating payload tesirine have recently entered Phase I clinical trials including ADCT-30120, ADCT-40221, ADCT-401/MEDI3726 and ADCT-502. The current study reports the preclinical pharmacology and mechanism of action of SG3199, confirming the properties which contribute to its success as a novel ADC warhead (see page 2, 1st and 2nd ¶). SG3199 was potently cytotoxic in many cell lines and showed a multi-log differential activity. The 17 haematological cell lines were, in general, more sensitive to SG3199 than the 21 solid tumour cell lines. The solid tumour cell lines represented seven organ sites and sensitivity across all sites was observed (page 3, 2nd ¶).
Hartley et al teaches that several important properties of the mechanism of action and pharmacology of PBD dimer SG3199 contribute to its emerging clinical success as a warhead in next-generation ADCs. Firstly, it is potently cytotoxic, showing activity across a wide range of both solid tumour and haematological cancers. No clear differential sensitivity was observed and the two least sensitive tumour cell lines still had GI50 values of 1 nM. This is an important factor for the utility of an ADC warhead across multiple tumour pathologies and is in contrast to tubulin inhibitor-based warheads which are less effective against some tumor types. The high potency of SG3199 is also an important advantage in ADCs utilising payload tesirine being able to treat tumors with low copy number antigen targets (see page 6, under Discussion).
Further Hartley et al teach that SG3199 has a very short half-life, an important property in the context of an ADC warhead. ADCs with the enzyme cleavable linker-containing payload tesirine, which employs SG3199, have been shown to have a significant bystander effect. This is an important advantage when targeting tumors with a heterogenous target antigen expression. The short half-life of the released SG3199 warhead, however, ensures that the bystander effect is restricted and that systemic accumulation of free drug, which could contribute to off-target toxicity, is limited. In addition, ADCs often have a very long half-life in circulation (10–14 days in the case of Rova-T in humans). The very short half-life of SG3199 ensures that any premature release in circulation would also not result in accumulation of SG3199 to levels that cause systemic toxicity. In summary, SG3199 has several properties which contribute to its success as an ADC warhead. It is the war head component of tesirine which is the payload of several ADCs including rovalpituzumab tesirine, ADCT 301, ADCT-402, ADCT-401/MEDI3726 and ADCT-502 currently in different stages of clinical development (see last ¶).
Those of skill in the art would have had reason to use the tesirine (SG3249) of the Hartley as a substitute for the Biologically Active Molecule taught in WO/2014/145090 because, like the compounds taught in WO/2014/145090, tesirine (SG3249) is warhead/payload component to treat tumors with low copy number antigen targets . Substituting a known element for another, to yield the known result, is obvious. See KSR, 550 U.S. at 416, 421 (2007).
"[W]hen a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable result." KSR Int'l v. Teleflex Inc., 550 U.S. 398,416 (2007).
The claimed functional properties recited in claims 20-21 are considered inherent properties of the H1H1863N2-tesirine in the absence of evidence to the contrary.
Claims 12 and 14 are included because H1H1863N2 is fully antibody having human Fc derived from IgG1 (i.e., H1) comprising SEQ ID NOs: 18 and 22.
It is noted claim 37 is constructed as product by process. However, the patentability of a product does not depend on its method of production. In re Thorpe, 227 USPQ 964, 966 (Fed. Cir. 1985), MPEP 2113. It is Applicant burden to show that the manufacturing process steps would be expected to impart distinctive structural characteristics to the final product.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
11. Claims 1-3, 6, 8, 10-12, 14, 16, 20-22, 24, 27, 29, 33, 34 and 37 are rejected under 35 U.S.C. 103 as being unpatentable over US 11608380 B2 in view of Tiberghien (ACS Med Chem Lett. 2016;7(11):983–987).
The teachings of `380 patent have been discussed, supra. The `380 patent further teaches an anti-EGFRvIII antibody-drug conjugate inhibits tumor growth in in vivo EGFRvIII-positive breast cancer allograft models. Two different antibody-drug conjugates of the exemplary anti-EGFRvIII antibody H1H1863N2 were tested for their ability to inhibit tumor growth in vivo. A first ADC was produced by conjugating H1H1863N2 to the maytansinoid toxin DM1 via a non-cleavable MCC linker to produce “H1H1863N2-MCC-DM1.” A second ADC was produced by conjugating H1H1863N2 to a modified version of DM1 attached to a novel cleavable linker, referred to as “M0026” (also known as “compound 7” in WO2014/145090, the disclosure of which is incorporated by reference herein in its entirety), to yield “H1H1863N2-M0026.” When tested for cytotoxicity in vitro against MMT/EGFRvIII cells, H1H1863N2-MCC-DM1 exhibited an IC.sub.50 of 12 nM whereas H1H1863N2-7 exhibited an IC.sub.50 of 0.8 nM based on drug equivalents (see Example 12, col., 42, lines 15+). The `380 patent demonstrate superiority of the tumor growth inhibition induced by H1H1863N2-M0026 (i.e., cleavable linker).
The reference teachings differ from the claimed invention only in the recitation that the encoded immunoglobulin further comprising conjugating tesirine to one or more of the immunoglobuline in claim 34 which result in an ADC in claims 37 and 1-3, 6, 8, 10-11, 20-22, 24, 27, 29.
Tiberghien et al teach preparation of SG3249 antibody−drug conjugates (see supporting information, page 986, left col, top ¶) that SG3249 conjugation to all antibodies was highly efficient, as illustrated by a readily tunable stochastic ADC average drug-to antibody ratio (DAR of 2.5 in this instance; the DAR can be tuned by varying the amount of TCEP reducing agent) and site-specific ADC DAR of 1.8 (90% conjugation efficiency). SG3249 was found readily soluble in the 10% DMSO aqueous conjugation buffer (see page 985m right col., 2nd ¶) The conjugation process reproducibly delivered high monomeric purity ADCs in high yields, on microgram to gram scale (page 986, left col, top ¶).
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Those of skill in the art would have had a reason to use tesirine taught by Tiberghien as a substitute for the warhead taught by the `380 patent using the preparation of SG3249 antibody−drug conjugates procedures taught by Tiberghien et al because tesirine is potent antitumor activity with desirable physicochemical properties such as favorable hydrophobicity and improved conjugation characteristics.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
12. Claims 1-3, 6, 8, 10-12, 14, 20-22, 24, 27, 29, 33 and 37 are rejected under 35 U.S.C. 103 as being unpatentable over WO/2014/145090 in view of Hartley et al (Nature, (2018) 8:10479) and Lhospice et al., (Innate Pharma, ADC Summit 2013).
The teachings of the `090 publication and Hartley et al have been discussed, supra.
Lhospice et al teaches that Bacterial Transglutaminase (BTG) allows coupling on endogenous Q295 from an aglycosylated antibody. Here, the work relates to ADCs synthesis through BTG approach on mAbs with single point mutations and the study of stability, pharmacokinetics, as well as in vitro and in vivo efficacy of resulting BTG-ADCs. BTG two-step process leads to ADCs with DAR of exactly 2.0 or 4.0 for antibodies with N297S or N297Q single point mutation respectively. BTG-ADCs were stable in buffer and ex vivo in human and cynomolgus plasma. BTG-ADCs showed no DAR variation in vivo in rats over 15 days and a lower clearance of the total antibody compared to ADCETRIS®. Finally, BTG-ADCs with a DAR of 4.0 showed similar in vitro potency and efficacy compared to ADCETRIS® as well as similar in vivo efficacy in a xenogeneic tumoral model (see abstract).
Those of skill in the art would have had a reason to synthesis a site-specific antibody-drug conjugates of H1H1863N2 taught by `090 publication having a DAR of four by attaching the linking moieties to H1H1863N2 having N297Q mutations as taught by Lhospice et al.
N297Q mutation would result in claimed SEQ ID NO: 20 (human IgG1 Fc mutant (N297Q)).
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
13. 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.
14. Claims1-3, 6, 8, 10-12, 14, 16, 19-22, 24, 27, 29, 33-34 and 37 are rejected on the ground of nonstatutory double patenting as being unpatentable over:
(a) claims 1-27 of U.S. Patent No. 10738124.
(b) claims 1-13 of U.S. Patent No. 10047160.
(c) claims 1-9 of U. S. Patent No. 9475875; each in view of Hartley et al (Nature, (2018) 8:10479), Tiberghien (ACS Med Chem Lett. 2016;7(11):983–987) and Lhospice et al., (Innate Pharma, ADC Summit 2013).
Although the claims at issue are not identical, they are not patentably distinct from each other because:
(a) The claims of the `124 are directed to anti-EGFRvIII antibody, H1H1863N2, comprising the claimed SEQ ID NOs, wherein the antibody or antigen-binding fragment is conjugated to a cytotoxin, wherein the cytotoxin is selected from the group consisting of 1-(2chloroethyl)-1,2-dimethanesulfonyl hydrazide, 1,8-dihydroxy-bicyclo[7.3.1]trideca-4,9-diene-2,6-diyne-13-one, 1-dehydrotestosterone, 5-fluorouracil, 6-mercaptopurine, 6-thioguanine, 9-amino camptothecin, actinomycin D, amanitins, aminopterin, anguidine, anthracycline, anthramycin (AMC), auristatins, bleomycin, busulfan, butyric acid, calicheamicins, camptothecin, carminomycins, carmustine, cemadotins, cisplatin, colchicin, combretastatins, cyclophosphamide, cytarabine, cytochalasin B, dactinomycin, daunorubicin, decarbazine, diacetoxypentyldoxorubicin, dibromomannitol, dihydroxy anthracin dione, disorazoles, dolastatin, doxorubicin, duocarmycin, echinomycins, eleutherobins, emetine, epothilones, esperamicin, estramustines, ethidium bromide, etoposide, fluorouracils, geldanamycins, gramicidin D, glucocorticoids, irinotecans, leptomycins, leurosines, lidocaine, lomustine (CCNU), maytansinoids, mechlorethamine, melphalan, mercatopurines, methopterins, methotrexate, mithramycin, mitomycin, mitoxantrone, N8-acetyl spermidine, podophyllotoxins, procaine, propranolol, pteridines, puromycin, pyrrolobenzodiazepines, rhizoxins, streptozotocin, tallysomycins, taxol, tenoposide, tetracaine, thioepa chlorambucil, tomaymycins, topotecans, tubulysin, vinblastine, vincristine, vindesine, vinorelbines, and derivatives thereof. The `124 also claims methods for treating a cancer or tumor expressing EGFRvI.
(b) The claims of `160 patent are directed to methods of treating cancer with ADC comprising anti-EGFRvIII antibody, H1H1863N2 and cytotoxin including biotoxins, chemotherapeutic agents and radioisotopes.
(c) The claims of the `875 patent are directed to anti-EGFRvIII antibody, H1H1863N2, comprising the claimed SEQ ID NOs, wherein the antibody or antigen-binding fragment is conjugated to a cytotoxin, wherein the cytotoxin is selected from the group consisting of maytansinoids, auristatins, tomaymycins, duocarmycins, 225Ac, 227Th, and any derivatives thereof.
The teachings of Hartley et al, Tiberghien et al and Lhospice et al have been discussed, supra.
Those of skill in the art would have had reason to use the tesirine (SG3249) of the Hartley as a substitute for the cytotoxin taught in `124, `160 and `875 patents because, like the compounds taught in `124, 160 and 875 patents, tesirine (SG3249) is cytotoxin/warhead/payload component to treat tumors with low copy number antigen targets . Substituting a known element for another, to yield the known result, is obvious. See KSR, 550 U.S. at 416, 421 (2007).
Those of skill in the art would have had a reason to use tesirine taught by Tiberghien as a substitute for the warhead taught by the `124, `160 and `875 patents using the preparation of SG3249 antibody−drug conjugates procedures taught by Tiberghien et al because tesirine is potent antitumor activity with desirable physicochemical properties such as favorable hydrophobicity and improved conjugation characteristics.
15. No claim is allowed.
16. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAHER M HADDAD whose telephone number is (571)272-0845. The examiner can normally be reached on Monday-Friday from7:00AM to 4:30PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu, can be reached at telephone number 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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June 18, 2026
/MAHER M HADDAD/ Primary Examiner, Art Unit 1644
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