13 results about "Paratope" patented technology

A major challenge in the field of antibody-based therapeutics is the development of antibodies that have longer duration of action, longer half-life and can be delivered to a patient at lower doses. The current methods to achieve this aim depend on the engineering modification of the pH-dependent antigen binding properties of the antibodies, which is very strenuous and generally requires further optimization of the pH-sensitive interactions in a low-throughput, individualized manner because these methods depend mainly on the introduction of histidine mutations in specific antibody complementarity determining regions (CDRs). In the present invention, the inventors provide antibodies and other antigen-binding proteins that carry mutations outside of the complementals, thereby conferring universal pH-sensitive binding properties to the antibodies. The invention also relates to methods of isolating and generating said antigen binding proteins, compositions and medical uses thereof.

Described and featured herein are biparatopic antibodies that specifically bind Fms Related Receptor Tyrosine Kinase 3 (FLT-3), antibody drug conjugates (ADC's) comprising such antibodies, as well as methods of using such antibodies and ADC for the treatment of diseases, such as cancer. Particularly effective are biparatopic antibodies in which one binding arm binds to an epitope of FLT3 that is located N-terminal of the D1 domain and the other binding arm binds to an epitope located on or includes a portion of domain D3.

The application relates to cytokine receptor agonists comprising: i) a first PD-1 binding domain capable of binding a first epitope on PD-1, ii) a second PD-1 binding domain capable of binding a second epitope on PD-1, iii) an IL2Rγ binding domain, iv) an IL2Rβ binding domain, and v) an Fc region, and wherein the first and second PD-1 binding domains do not compete for binding on PD-1. The PD1-binding domains simultaneously bind the PD-1 and the IL-2 receptor-binding domains bind subunits of an IL-2 receptor complex. Biparatopic assembly of the IL-2 receptor-binding domains in the presence of PD-1 allows to selectively activate IL-2 receptors and effectively mimic cytokine activity in a targeted manner.

A method for selecting camelid nanobodies from an array library collected from B cells of a camelid animal immunized with an antigen is provided. The method comprises (a) (i)phenylalanine (F) at position 42 (IMGT number), and (ii)a short hinge, and (iii)two or more cysteines in the nanobody sequence, and (iv)glutamine (Q) at position 123 (IMGT number), and (v)a low immunogenicity index, and (vi)a non-conventional VHH derived from germline IGHV3, or valine (V) included at position 42 (IMGT number), and (vii)a non-conventional VHH derived from germline IGHV4, or isoleucine (I) included at position 42 (IMGT number), and (viii)histidine (H), aspartic acid (D), or glutamic acid (E) in the CDR region, and (ix)histidine (H), aspartic acid (D), or glutamic acid (E) in the top 3 amino acid residues of the nanobody sequence, the FR2 region, or the top 16 amino acid residues of the FR3 region, and (x)tyrosine (Y) at position 42 (IMGT number), and a nanobody having a cyclic concave paratope structure arrangement, or (xi)phenylalanine (F) at position 42 (IMGT number), and a nanobody having a convex paratope structure arrangement, identifying a camelid nanobody having at least one of the features, and (b)measuring one or more biological activities of the nanobody identified in step (a).

The present disclosure provides monoclonal and recombinant anti-CDH17 antibodies (including CDH17 biparatopic and CDH17xCD3 bispecific antibodies and CDH17-binding fragments. Such antibodies and binding fragments are useful for the treatment of cancer, cither alone or in combination with other agents.

Characterization of the binding dynamics at the interface between any two proteins that specifically interact plays a role in myriad biomedical applications. The methods disclosed herein provide for the high-throughput characterization of the specific interaction at the interface between two protein binding partners and the identification of functionally significant mutations of one or both protein binding partners. For example, the methods disclosed herein may be useful for epitope and paratope mapping of an antibody-antigen pair, which is useful for the discovery and development of novel therapies, vaccines, diagnostics, among other biomedical applications.

Provided herein are, inter alia, antibodies (e.g., humanized antibodies, chimeric antibodies, monoclonal antibodies, biparatopic antibodies, antibody fragments (e.g., Fab')), which bind CD38 with high efficiency and specificity. Inter alia, are provided biparatopic antibodies that bind CD38 specifically and effectively. The biparatopic antibodies provided herein may have an increased binding avidity relative to the monoclonal antibodies they are derived from and are specifically useful for therapeutic and diagnostic purposes.

Provided is a method of selecting a camelid nanobody from a library of camelid nanobody sequences collected from B cells from a camelid immunized with an antigen. The method comprises: (a) identifying a camelid nanobody that has at least one of the following features (i) a phenylalanine (F) at position 42 (IMGT numbering); (ii) a short hinge; (iii) two or more cysteines in the nanobody sequence; (iv) a glutamine (Q) at position 123 (IMGT numbering); (v) low immunogenicity metric; (vi) non-classic VHH derived from germline IGHV3 or a valine (V) at position 42 (IMGT numbering); (vii) non-classic VHH derived from germline IGHV4 or an isoleucine (I) at position 42 (IMGT numbering); (viii) a histidine (H), aspartic acid (D) or glutamic acid (E) in the CDR region; (ix) a histidine (H), aspartic acid (D) or glutamic acid (E) in the first three amino acid residues, the FR2 region, or the first sixteen amino acid residues of the FR3 region of the nanobody sequence; (x) a tyrosine (Y) at position 42 (IMGT numbering), and the nanobody having a loop, concave paratope structure configuration; or (xi) a phenylalanine (F) at position 42 (IMGT numbering), and the nanobody having a convex paratope structure configuration; and (b) measuring one or more biological activities of the nanobody identified in step (a).

Provided herein are anti-PD-L1 multiparatopic antibody constructs that include a plurality of antigen-binding fragments, wherein a first antigen-binding fragment of the plurality of antigen-binding fragments binds specifically to a first PD-L1 epitope, and wherein a second antigen-binding fragment of the plurality of antigen-binding fragments binds specifically to a second PD-L1 epitope.

The present disclosure provides monoclonal and recombinant anti-CDH17 antibodies (including CDH17 biparatopic and CDH17xCD3 bispecific antibodies and CDH17-binding fragments. Such antibodies and binding fragments are useful for the treatment of cancer, either alone or in combination with other agents.

The application relates to antigen binding molecules comprising a pair of biparatopic target-binding domains, a pair of cytokine receptor-binding domains and an Fc domain, wherein the target-binding domains simultaneously bind the target antigen and the cytokine receptor-binding domains bind subunits of a cytokine receptor complex. Biparatopic assembly of the cytokine receptor-binding domains in presence of the target antigen allows to selectively activate cytokine receptors and effectively mimic cytokine activity in a targeted manner.

The present invention relates to T cell engager masking molecules, and methods related thereto, that contribute to reduce the severity of cytokine release syndrome, wherein said molecules comprise (i.) a binding peptide which is deprived of an isomerization site and which binds to a T-cell engaging paratope of a bispecific T cell engager molecule (TCE), (ii.) a linker, and (iii.) a half-life extending polymer.

This disclosure provides an antibody design method based on flow matching and graph neural networks. The method comprises the following steps: Step 1, input parsing and initial antibody structure construction; Step 2, antigen epitope surface modeling; Step 3, local generation of binding regions based on flow matching; Step 4, global propagation of a surface-enhanced message encoder; Step 5, sequence-structure joint convergence generation, ultimately outputting a full-atom 3D antibody structure and paratope residue sequences. The above process achieves more accurate interface modeling and structure generation by constructing a flow matching generation process in the binding region and utilizing a global geometric message passing mechanism driven by antigen surface point clouds; simultaneously, by restricting flow matching computation to local regions, the computational overhead of generating large molecular structures is effectively reduced.