US 11,767,367 B2Granted

Monoclonal antibody neo-201 for the treatment of human carcinomas

AssigneePrecision Biologics, Inc.

InventorsPhilip M. Arlen, Kwong Y. Tsang

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Abstract

NEO-201 is a humanized IgG1 monoclonal antibody (mAb) that is highly reactive against the majority of tumor tissues from many different carcinomas, including colon, pancreatic, stomach, lung, breast, and uterine cancers, but the overwhelming majority of normal tissues are not recognized by this antibody. Functional assays revealed that NEO-201 is capable of mediating both antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) against tumor cells. Furthermore, the growth of human pancreatic xenograft tumors in vivo was largely attenuated by treatment with NEO-201 both alone and in combination with human peripheral blood mononuclear cells (PBMC) as an effector cell source for ADCC. In vivo biodistribution studies in human tumor xenograft-bearing mice revealed that NEO-201 preferentially accumulates in the tumor but not organ tissue. A single-dose toxicity study in non-human primates demonstrated safety and tolerability of NEO-201, as a transient decrease in circulating neutrophils was the only related adverse effect observed.

Claims19

Dependent claims

A method of promoting antibody-dependent cell-mediated cytotoxicity (ADCC) or natural killer (NK) cell-mediated killing of carcinoma cells which express a CEACAM antigen bound by the NEO-201 antibody in a patient in need thereof consisting essentially of administering:

(i) a NEO-201 antibody to said patient in need thereof, wherein said NEO-201 antibody comprises a heavy chain wherein the CDR1 comprises the amino acid sequence of SEQ ID NO:
32, the CDR2 comprises the amino acid sequence of SEQ ID NO:
33, and the CDR3 comprises the amino acid sequence of SEQ ID NO:
34;
and comprises a light chain wherein the CDR1 comprises the amino acid sequence of SEQ ID NO:
35, the CDR2 comprises the amino acid sequence of SEQ ID NO:
36, and the CDR3 comprises the amino acid sequence of SEQ ID NO:
37;
and
(ii) an IL-15 agonist or an IL-15 superagonist, wherein said moieties (i) and (ii) are administered separately or in combination, under conditions whereby the IL-15 agonist or the IL-15 superagonist enhances ADCC or NK cell-mediated killing of carcinoma cells by the NEO-201 antibody in said patient compared to the amount of ADCC or NK cell-mediated killing of carcinoma cells if the same dose of NEO-201 antibody is administered in the absence of said IL-15 agonist or an IL-15 superagonist;
and
wherein said patient is natural killer (NK)-depleted prior to or at the time of said administering;
and/or said patient is severely NK-depleted prior to or at the time of said administering.

10 more elements

Dependencies are inferred from the claim text.

Facts

Application: 16/761,404Filed 2 Nov 2018 · us provisional application
Priority: 3 Nov 2017
Published: US 2020/0362053 A119 Nov 2020
Granted: 26 Sep 2023
Term ends: Not estimatedThe source records don’t support an estimate.

Classification20 codes

C07K 16/30
Against receptors, cell surface antigens or cell surface determinants: from tumour cells
A61K 38/05
Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof: dipeptides
A61K 38/1725
From mammals: complement proteins, e.g. anaphylatoxin, C3a or C5a
A61K 38/20
Cytokines; Lymphokines; Interferons: interleukins [IL]