WO2004006955A1 - Super humanized antibodies - Google Patents
Super humanized antibodies Download PDFInfo
- Publication number
- WO2004006955A1 WO2004006955A1 PCT/US2002/022011 US0222011W WO2004006955A1 WO 2004006955 A1 WO2004006955 A1 WO 2004006955A1 US 0222011 W US0222011 W US 0222011W WO 2004006955 A1 WO2004006955 A1 WO 2004006955A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- human
- sequences
- antibody
- cdr
- sequence
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2803—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily
- C07K16/2818—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against the immunoglobulin superfamily against CD28 or CD152
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/46—Hybrid immunoglobulins
- C07K16/461—Igs containing Ig-regions, -domains or -residues form different species
- C07K16/464—Igs containing CDR-residues from one specie grafted between FR-residues from another
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/54—F(ab')2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/567—Framework region [FR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2319/00—Fusion polypeptide
Definitions
- the invention relates to methods of humanizing antibodies, particularly to humanizing antibodies by making chimeric antibodies containing CDR sequences from a non-human antibody and framework sequences of human antibodies, more particularly to methods of selecting appropriate human antibody framework sequences for performing the humanization, and still more particularly to using canonical CDR structure types of the non-human antibody in comparison to germline canonical CDR structure types of human antibodies as the basis for selecting the appropriate human framework sequences for a humanized antibody.
- Antibodies are natural proteins that the vertebrate immune system forms in response to foreign substances (antigens), primarily for defense against infection.
- antibodies have been induced in animals under artificial conditions and harvested for use in therapy or diagnosis of disease conditions, or for biological research.
- Each individual antibody producing cell produces a single type of antibody with a chemically defined composition, however, antibodies obtained directly from animal serum in response to antigen inoculation actually comprise an ensemble of non-identical molecules (i.e, polyclonal antibodies) made from an ensemble of individual antibody producing cells.
- Hybridoma technology provided a method to propagate a single antibody- producing cell for an indefinite number of generations with a screening method to identify clones of cells producing an antibody that would react with a particular antigen.
- Development of this technology allowed production in unlimited quantities of structurally identical antibodies with essentially any desired antigenic specificity.
- Such antibodies are commonly called monoclonal antibodies, and most originate from rodents. Sequencing of monoclonal antibody genes allowed the primary amino acid structure of the antibody be defined.
- variable region domains of the light and heavy chains are responsible for the interaction between the antibody and the antigen.
- the joining domains connecting variable domains to constant domains are situated in a region remote from the site of antigen binding, therefore, the joining domains between variable and constant domains generally do not interfere with antigen binding.
- Chimeric antibody molecules having mouse variable domains joined to human constant domains usually bind antigen with the same affinity constant as the mouse antibody from which the chimeric was derived. Such chimeric antibodies are less immunogenic in humans than their fully murine counterparts.
- INFLLXIMABTM a widely prescribed chimeric antibody that is considered safe, induced a human anti-chimeric antibody response in 7 out of 47 Crohns Disease patients.
- variable domains contain contiguous tracts of peptide sequence that are conserved within a species, but which differ between evolutionarily remote species, such as mice and humans.
- variable domains contain contiguous tracts of peptide sequence that are conserved within a species, but which differ between evolutionarily remote species, such as mice and humans.
- other contiguous tracts are not conserved within a species, but even differ even between antibody producing cells within the same individual.
- contacts between antibody and antigen occur principally through the non-conserved regions of the variable domain.
- the molecular architecture of antibody variable domains is sufficiently similar across species that correspondent amino acid residue positions between species may be identified based on position alone, without experimental data.
- Kabat and Wu calculated variability, by which is meant the finding of few or many possible amino acids when variable domain sequences are aligned. They identified three contiguous regions of high variability embedded within four less variable contiguous regions. Other workers had previously noted variability approximately in these regions (hypervariable regions) and posited that the highly variable regions represented amino acid residues used for antigen binding. Kabat and Wu formally demarcated residues constituting these variable tracts, and designated these "complementarity determining regions" (CDRs), referring to chemical complementarity between antibody and antigen. A role in three- dimensional folding of the variable domain, but not in antigen recognition, was ascribed to the remaining less-variable regions, which are now termed "framework regions”. Fourth, Kabat and Wu established a public database of antibody peptide and nucleic acid sequences, which continues to be maintained and is well known to those skilled in the art.
- CDRs complementarity determining regions
- U.S. Pat. No. 5,693,761 to Queen et al discloses one refinement on Winter for humanizing antibodies, and is based on the premise that ascribes avidity loss to problems in the structural motifs in the humanized framework which, because of steric or other chemical incompatibility, interfere with the folding of the CDRs into the binding- capable conformation found in the mouse antibody.
- Queen teaches using human framework sequences closely homologous in linear peptide sequence to framework sequences of the mouse antibody to be humanized. Accordingly, the methods of Queen focus on comparing framework sequences between species. Typically, all available human variable domain sequences are compared to a particular mouse sequence and the percentage identity between correspondent framework residues is calculated.
- the human variable domain with the highest percentage is selected to provide the framework sequences for the humanizing project. Queen also teaches that it is important to retain in the humanized framework, certain amino acid residues from the mouse framework critical for supporting the CDRs in a binding-capable conformation. Potential criticality is assessed from molecular models. Candidate residues for retention are typically those adjacent in linear sequence to a CDR or physically within 6 A of any CDR residue. In other approaches, criticality of particular framework amino acid residues is determined experimentally once a low-avidity humanized construct is obtained, by reversion of single residues to the mouse sequence and assaying antigen binding as described by Riechmann et al, (1988). Another example approach for identifying criticality of amino acids in framework sequences is disclosed by U.S.
- the present invention meets this need by providing methods for making humanized antibody of high affinity and low immunogenicity without need for comparing framework sequences between non-human and human antibodies and also provides humanized antibodies made thereby. Rather than relying on human framework sequences as the point of analysis, the methods provided herein rely on comparing canonical CDR structure types of the non-human antibody to CDR structure types of human antibodies, particularly as encoded by human germline sequences, to identify candidate human antibody sequences from which to obtain appropriate human frameworks.
- a method of making a humanized antibody that includes the acts of obtaining a peptide sequence for a subject variable region encoded by a non-human mature antibody gene and identifying a first set of canonical CDR structure types for at least two CDRs within the non-human antibody variable region. Then A library of peptide sequences for human antibody variable regions for human antibodies is also obtained.
- the library contains sequences for human germline variable regions as encoded by germline nucleic acid segments. In other embodiments, however, the library may include mature human antibody sequences.
- the method includes identifying canonical CDR structure types (i.e., a second set of canonical CDR structure types) for at least two CDRs for each sequence within the library of human variable region sequences. From this library there is selected a subset of candidate sequences by comparing the first set of canonical CDR structure types to the second set of canonical CDR structure types (i.e., comparing the mouse canonical CDR structure types to the human canonical CDR structure types at corresponding locations within the variable region) and selecting those human sequences where the second set of canonical CDR structure is the same as the first set of canonical CDR structure types for the CDR sequences at corresponding locations within the non-human and human variable regions, respectively.
- canonical CDR structure types i.e., a second set of canonical CDR structure types
- the method uses these candidate human variable region sequences as a basis for constructing a chimeric molecule that includes at least two of the CDR sequences from the non-human variable region (e.g., of the mouse CDRs) combined with the framework regions from candidate human variable region sequences.
- the result of the construction is that the chimeric antibody contains each of the non-human CDR sequences substituted for each of the human CDR sequences at corresponding locations in the variable regions so that the framework sequences in the chimeric antibody differs from the candidate human framework sequences by no more than 10 amino acid residues.
- the framework sequences of the chimeric antibody differ from the human framework sequences by no more than 5 amino acid residues.
- the framework sequences of the chimeric antibody differs from the human framework sequences by no more than 2 amino acid residues.
- the act of constructing the chimeric antibody molecule includes constructing a nucleic acid sequence that encodes the chimeric antibody sequences.
- the method further includes ranking the members of the subset of candidated human sequences by comparing position by position similarity of amino acid residues of the non-human CDR sequences to the corresponding human CDR sequences according to a ranking criterion.
- the candidate of human sequences includes only the top 25% of the ranked members.
- the ranking criterion includes a score of amino acid identity between the non-human and human CDR sequences at corresponding residue positions of at least one CDR, or at least two CDRs, or most typically each corresponding CDR. In other embodiments, the ranking criterion includes a score of amino acid homology between the non-human and human CDRs. at corresponding residue positions of at least one, at least two, or each of the corresponding CDRs. In still other embodiments , the ranking criterion includes both a score of amino acid identity as well as a score of amino acid homology for at least one, at least two or each of the corresponding CDRs. The method may be practiced using CDRs as defined by differing systems.
- the CDRs are Kabat defined CDRs, in other embodiments, the CDRs are Chothia defined CDR loops.
- the method is not limited to strictly using the exact CDR sequences of the non-human source or exact sequences of the human frameworks from the member sets.
- the method may also include substituting at least one amino acid residue of the non-human CDR sequences with a different amino acid, provided however, that no more than 4 residues are substituted in any of non-human light chain CDR1, light chain CDR2, light chain CDR 3, heavy chain CDR1, or heavy chain CDR3 and no more than 10 amino acids are substituted in non-human heavy chain CDR2.
- the method may also include substituting at least one but no more than 10 amino acid residues of the human framework sequence with a different amino acid residue.
- the method also recognizes that on certain occasions the non-human variable region may include a CDR sequence having a canonical type absent from human variable regions.
- each of three non-human CDRs is a light chain CDR
- the act of selecting the human sequences includes selecting a human variable region sequence with a CDR of a different canonical type than the absent non-human CDR type at the corresponding location, providing only that the different canonical human CDR type has a length no more than two amino acid residues smaller or larger than the length of the absent canonical CDR structure type of the non-human CDR.
- the act includes selecting a human sequence with a canonical type 2 CDR at the corresponding location, or if the non-human CDR sequences is of canonical type 5 then the act includes selecting a human sequence with a canonical type 4 or 3 CDR at the corresponding location.
- the non-human variable region is a mouse variable region.
- the library of human variable region sequences includes a human V k N ⁇ , V H , J H , J or J sequence as the source of the human frameworks.
- the method includes assembling a chimeric antibody having both a chimeric variable light chain and a chimeric variable heavy chain, typically with human frameworks from V k and V H sequences.
- the chimeric variable light chains and chimeric variable heavy chains are formed into an Fab fragment, or a (Fab) 2 molecule, or a single chain Fv molecule, or the chimeric variable light chains and chimeric heavy chains are assembled with a human antibody constant region to form a complete antibody.
- the methods are applicable to converting a subject antibody sequence of any subject species to a less immunogenic form suitable for use in an object species by making chimeric antibodies containing framework sequences of the object species in combination with CDRs from the subject species.
- the foregoing methods are the same in the acts performed, where the variable region may be from any subject species and the object variable region may be from any object species for which the antibody will be used.
- a subject antibody may be chimierzied with framework sequences from bovine, porcine, murine or equine sources to form bovinized, porcinized, murinized, or equinized, respectively.
- the invention provides compositions that include the chimeric antibody molecules made according to the disclosed methods. Because, the methods utilize a novel way of identifying the appropriate object framework sequence to combine with subject CDR sequences, the resulting chimeric antibodies made are also novel. Accordingly, there is herein provided, a humanized antibody that includes a chimeric antibody variable region containing at least two non-human CDR sequences fused adjacent to human variable region framework sequence.
- the human framework sequences are selected from a subset of framework sequences characterized by having no more than 10 amino acid residues that differ from a framework sequences in a human antibody variable region having at least two human CDR sequences with the same canonical structure type as the non-human CDR sequences for at least two corresponding CDR positions between the variable region of the chimeric antibody and the human antibody.
- the non-human variable region CDRs are typically from a mouse.
- the human variable region sequence is typically a V k ⁇ , V H , J H , J k or 1 sequence.
- the chimeric antibody includes chimeric antibody sequences for each of a variable light chain and a variable heavy chain.
- the chimeric variable light chains and chimeric variable heavy chains are formed into an Fab fragment, or a (Fab) 2 molecule, or a single chain Fv molecule, or the chimeric variable light chains and chimeric heavy chains are assembled with a human antibody constant region in the form of a complete antibody.
- the human variable region sequence is a sequence from a human germline variable region fragment.
- the human variable regions sequence is a sequence from a human mature antibody.
- the humanized antibody has a dissociation constant for its antigen of at least 10 6 M “1 , preferably at least 10 7 M "1 and more preferably at least 10 M " .
- the humanized antibody of does not elicit an immune response when administered to a human.
- Particular embodiments exemplifying the invention included humanized antibodies that bind a scorpion venom antigen, that bind a human CD28 receptor, that bind human lysozyme, or that bind a human glutamic acid decarboxylase (GAD65).
- Figure 1 depicts a library of human germline V H gene segments.
- Figure 2 depicts a library of human germline V k gene segments.
- Figure 3 depicts a portion of mouse D1.3 (anti-chicken lysozyme) antibody variable light chain sequence and a selected subset of human germline V variable region sequences having canonical CDRs of the same type as the mouse DL.3 light chain sequence at corresponding locations.
- the subset is ranked by similarity of amino acid sequences between the DL.3 CDRs and the human CDRs, with the highest ranked sequence depicted first.
- Figure 4 depicts a portion of the mouse D1.3 antibody variable heavy chain sequence and a selected subset of human germline V H variable region sequences having canonical CDRs of the same type as the DL.3. The subset is ranked by similarity of amino acid sequences of the corresponding CDRs analogously to Figure 3.
- Figure 5 depicts amino acid sequences for a chimeric V k variable region and V H variable region for a humanized D1.3 antibody, illustrating one aspect of the invention.
- Figure 6 depicts a nucleic acid sequence for a DNA construct that encodes (and expresses) the humanized chimeric D1.3 antibody of Figure 5, illustrating another aspect of the invention.
- Figure 7 is a graph that illustrates antigen binding by the humanized D1.3 antibody, which has an affinity constant of greater than 10 8 M "1 , illustrating one embodiment of the invention.
- Figure 8 depicts a portion of a mouse variable light chain sequence of an anti-human CD28 antibody designated 9.3 and a selected subset of human germline V k variable region sequences having canonical CDRs of the same type as the mouse 9.3 variable light chain sequence at corresponding locations, which are ranked by similarity of amino acid sequences analagously to Figure 3.
- Figure 9 depicts a portion of the mouse variable heavy chain sequence for the 9.3 antibody and a selected subset of human germline V H variable region sequences having canonical CDRs of the same type as the mouse variable heavy chain sequence at corresponding locations also ranked by similarity of amino acid sequences.
- Figure 10 depicts a humanized anti-human CD28 (Hu.9.3) Fab fragment with chimeric variable heavy and variable light chains, illustrating another embodiment of the invention.
- Figure 11 is a graph that illustrates antigen binding by Hu9.3 Fab fragment, which has an affinity constant of greater than 10 6 M "1 , illustrating one embodiment of the invention
- Figure 12. depicts a humanized anti-scorpion toxin Fab fragment with chimeric variable heavy and variable light chains, illustrating another embodiment of the invention.
- Figure 13. depicts a humanized anti-human glutamic acid decarboxylase
- FIG. 14 is a graph that illustrates antigen binding by the humanized anti GAD65 Fab fragment, which has an affinity constant of greater than 10 11 M "1 , illustrating one embodiment of the invention
- a “mature antibody gene” is a genetic sequence encoding an immunoglobulin that is expressed, for example, in a lymphocyte such as a B cell, in a hybridoma or in any antibody producing cell that has undergone a maturation process so that the particular immunoglobulin is expressed.
- the term includes mature genomic, cDNA or other nucleic acid sequence that encodes such mature genes, which have been isolated and/or recombinantly engineered for expression in other cell types.
- Mature antibody genes have undergone various mutations and rearrangements that structurally distinguish them from antibody genes encoded in all cells other than lymphocytes.
- Mature antibody genes in humans, rodents, and many other mammals are formed by fusion of V and J gene segments in the case of antibody light chains and fusion of V, D, and J gene segments in the case of antibody heavy chains.
- Many mature antibody genes acquire point mutations subsequent to fusion, some of which increase the affinity of the antibody protein for a specific antigen "Germline antibody genes" or gene fragments are immunoglobulin sequences encoded by non-lymphoid cells that have not undergone the maturation process that leads to genetic rearrangement and mutation for expression of a particular immunoglobulin.
- FIG. 1 and Figure 2 show peptide sequences for human germline antibody genes encoding human variable heavy region (V H ) and variable light region (V ) antibodies (i.e.,. immunoglobulins). Each of these list of sequences exemplify a library of human antibody genes, particularly a library of human germline antibody genes.
- a CDR is the complement determining region within antibody variable sequences.
- CDRl variable heavy and variable light sequences
- CDR2 variable heavy and variable light sequences
- CDR3 variable heavy and variable light sequences
- the exact boundaries of these CDRs have been defined differently according to different systems, however, all have overlapping residues in what constitute the so called “hypervariable regions" within the variable sequences.
- the system described by Kabat (CITE) not only provides an unambiguous residue numbering system applicable to any variable region of an antibody, but ⁇ also provides precise fesidueTboundaries defininglhe three CT Rs These CDRs may be referred to as Kabat CDRs.
- Chothia and coworkers found that certain sub portions within Kabat CDRs adopt nearly identical peptide backbone conformations, despite having great diversity at the level of amino acid sequence. These sub portions were designated as LI, L2 and L3 or HI, H2 and H3 where the "L” and the "H” designates the light chain and the heavy chains regions, respectively. These regions may be referred to as Chothia CDRs, which have boundaries that overlap with Kabat CDRs. Table I illustrates the overlap of Chotia and Kabat CDRs according to the residue numbering system of Kabat.
- Framework or “framework sequence” are the remaining sequences of a variable region minus the CDRs. Because the exact definition of a CDR sequence can be determined by different systems, the meaning of a framework sequences is subject to correspondingly different interpretations. To clarify the meaning used herein, a framework sequence means those sequences within the variable region of an antibody other than those defined to be CDR sequences, so that the exact sequence of a framework depends only on how the CDR is defined. For example, the CDRs used in the methods provided herein are usually a subset of what is considered a Kabat CDR, but in the case of CDRl of heavy chains for example, also includes residues that are classified as framework residues in the Kabat system.
- Canonical CDR structure types are the structure types designated by Chothia (CITE). Chothia and coworkers found that critical portions of the CDRs of many antibodies adopt nearly identical peptide backbone conformations, despite great diversity at the level of amino acid sequence. Accordingly, Chothia defined for each CDR in each chain one or a few "canonical structures". Each canonical structure specifies primarily a set of peptide backbone torsion angles for a contiguous segment of amino acid residues forming a loop. The canonical CDR structure types defined by Chothia are listed in Table ⁇ . TABLE ⁇
- Co ⁇ esponding CDRs refer relatively to the CDRs between two different variable sequences that correspond in position within the two different variable sequences.
- a mouse light chain CDRl corresponds to a human light chain CDRl, and vice a versa, because each maps to a defined position in a Kabat numbering system, whether or not the actual boundary of the CDR is defined by Kabat, Chothia or some other system.
- corresponding residues, sequences or amino acids refer relatively to the residue positions between two different peptide sequences mapped by the Kabat numbering system.
- CDR grafting The objective of the methods provided herein, which may be called CDR grafting, method is to provide a prescription for arriving at appropriate human framework sequence for humanizing a subject non-human antibody.
- the choice of the humanized framework sequence was based on comparing the human framework to the subject (murine) frameworks .
- the basis of the methods herein described are to chose the human antibody to provide the humanized framework based on similarity of its CDRs to those of the subject antibody, without regard to comparing the framework sequences between the two antibodies.
- the similarity to the subject CDRs of candidate human antibody sequences is assessed for each domain at two levels. Primarily, identical three-dimensional conformations of CDR peptide backbones are sought. Experimentally determined atomic coordinates of the subject CDRs are seldom available, hence three-dimensional similarity is approximated by determining Chothia canonical structure types of the subject CDRs and excluding from further consideration candidates possessing different canonical structures. Secondarily, residue-to-residue homology between subject CDRs and the remaining human candidate CDRs is considered, and the candidate with the highest homology is chosen.
- the criterion for ranking members of the selected set may be by amino acid sequence identity or amino acid homology or both.
- Amino acid identity is simple a score of position by position matches of amino acid residues. Similarity by amino acid homology is position by position similarity in residue structure of character. Homology may be scored, for example, according to the tables and procedures described by Henikoff and Henikoff, (1992) Amino acid substitution matrices from protein blocks, Proc. Natl. Acad. Sci 89: 10915-10919. or by the BLOSUM series described by Henikoff and Henikoff, (1996) .
- the steps of the methods are as follow: Determine the peptide sequences of the heavy and light chain variable domains of the subject antibody. These can be determined by any of several methods, such as DNA sequencing of the respective genes after conventional cDNA cloning; DNA sequencing of cloning products that have been amplified by the polymerase chain reaction from reverse transcripts or DNA of the subject hybridoma line; or peptide sequencing of a purified antibody protein.
- Canonical structure type 1 31, 32, 33, 34, 35.
- Canonical structure type 2 31, 32, 33, 34, 35, 35a.
- Canonical structure type 3 31, 32, 33, 34, 35, 35a, 35b.
- Canonical structure type 1 52, 53, 54, 55, 56.
- Canonical structure type 4 52, 52a, 52b, 52c, 53, 54, 55, 56.
- Canonical structure types 2 and 3 for heavy chain CDR2 have equal numbers of residues, hence must be distinguished by clues within their sequence, as discussed by Chothia et al (1992). The Kabat numbering of the segment containing these clues is: 52, 52a, 53, 54, 55.
- Canonical structure type 2 has Pro or Ser at position 52a and Gly or Ser at position 55, with no restriction at the other positions.
- Canonical structure type 3 has Gly, Ser, Asn, or Asp at position 54, with no restriction at the other positions. These criteria are sufficient to resolve the correct assignment in most cases.
- framework residue 71 is commonly Ala, Val, Leu, He, or Thr for canonical structure type 2 and commonly Arg for canonical structure type 3.
- Heavy chain CDR3 is the most diverse of all the CDRs. It is generated by genetic processes, some of a random nature, unique to lymphocytes. Consequently, canonical structures for CDR3 have been difficult to predict. In any case, human germline V gene segments do not encode any part of CDR3; because the V gene segments end at Kabat position 94, whereas positions 95 to 102 encode CDR3. For these reasons, canonical structures of CDR3 are not considered for choosing candidate human sequences. For light chain CDRl, six canonical structure types are currently known for
- Each canonical structure type has a different number of residues, hence assignment of a canonical structure type to a new sequence is apparent from the Kabat numbering of residue positions 27 - 31.
- Canonical structure type 1 27, 29, 30, 31.
- Canonical structure type 2 27, 28, 29, 30,TT.
- Canonical structure type 3 27, 27a, 27b, 27c, 27d, 27e, 27f, 28, 29, 30, 31.
- Canonical structure type 4 27, 27a, 27b, 27c, 27d, 27e, 28, 29, 30, 31.
- Canonical structure type 5 27, 27a, 27b, 27c, 27d, 28, 29, 30, 31.
- Canonical structure type 6 27, 27a, 28, 29, 30, 31.
- Canonical structure type 1 91, 92, 93, 94, 95, 96, 97 (also with an obligatory Pro at position 95 and Gin, Asn, or His at position 90).
- Canonical structure type 3 91, 92, 93, 94, 95, 97.
- Canonical structure type 5 91, 92, 93, 94, 95, 96, 96a, 97.
- peptide sequences of human germline immunoglobulin VH and Vk gene fragments are considered for comparison. Most of these gene fragments have been discovered and have already been assigned to a canonical structure type (Chothia et al, 1992, Tomlinson et al,1995). Additional V gene fragments not disclosed by tehse references are provide herein and appear among those sequneces listed in Figure 1 and Figure 2.
- conformity of CDRl and CDR2 to the mouse canonical structure types is assessed, and genes that do not conform are excluded.
- conformity of CDRl and CDR2 of each human sequence to the canonical structure types of the subject antibody is first assessed.
- variable domain of the subject antibody is of a canonical structure type not available in the human genome
- human germline V genes that have three-dimensionally similar, but not identical, canonical structure types are considered for comparison.
- Such a circumstance often occurs with kappa chain CDRl in murine antibodies, including two of the examples described below. All 6 possible canonical structure types have been observed at this CDR in murine antibodies, whereas the human genome encodes only canonical types 2, 3, 4 and 6.
- a canonical CDR structure type having length of amino acid residues within two of the length of the amino acid residues of the subject non-human sequence may selected for the comparison.
- human Vk sequences with canonical structure type 2 should be used for comparison.
- human Vk sequences with either canonical structure type 3 or 4 should be used for comparison.
- mature, rearranged human antibody sequences can be considered for the sequence comparison. Such consideration might be be be warranted under a variety of circumstances, including but not limited to instances where the mature human sequence (1) is very close to germline; (2) is known not to be immunogenic in humans; or (3) contains a canonical structure type identical to that of the subject antibody, but not found in the human germline.
- residue to residue sequence identity and/or homology with the subject sequence is also evaluated to rank the candidate human sequences.
- residues evaluated are as follows.:
- residue-to-residue homology is first scored by the number of identical amino acid residues between the subject and the candidate human sequences.
- the human sequence used for subsequent construction of a converted antibody is chosen from among the 25 percent of candidates with the highest score.
- similarity between non-identical amino acid residues may be additionally be considered.
- Aliphatic-with-aliphatic, aromatic-with-aromatic, or polar-with-polar matches between subject and object residues are added to the scores.
- quantitative evaluation of sequence homology may be performed using amino acid substitution matrices such as the BLOSUM62 matrix of Henikoff and Henikoff (1992).
- Aa object sequence for the framework region C-terminal to CDR3 sequence is selected from the set of known human germline J segments.
- a preferred J peptide sequence is selected by evaluating residue to residue homology for each J segment for sequence positions for which CDR3 and J overlap, using the scoring criteria specified for the evaluation of candidate V genes as mentioned above.
- the J gene segment peptide sequence used for subsequent construction of a converted antibody is chosen from among the 25 percent of candidates with the highest score.
- the chimeric variable chain contains at least two CDRs from the subject non-human sequence, and framework sequences from the candidate human sequence.
- a chimeric light chain contains three CDRs from the subject non-human sequence and framework sequences from the candidate human sequence.
- a chimeric heavy chain contains at least two CDRs of the subject heavy chain, and framework sequence of the candidate human heavy chain.
- a chimeric heavy chin contains each of the CDRs from the subject heavy chain and the framework sequences of the candidate human heavy chain.
- a chimeric antibody heavy chain contains CDRs 1 and 2 from the subject non-human sequence and residues 50-60 for CDR3 and residues 61-65 of a CDR from the candidate human heavy chain, along with the framework sequences of the candidate human sequence.
- a chimeric heavy chain sequence contains each CDR from the subject non-human sequence, frameworks sequences 27-30 form the subject sequence, and the framework sequences from the candidated sequences. In all cases however, the chimeric antibody molecule contains no more than 10 amino acid residue in the framework sequence that differ from those in the framework sequence of the candidate human variable ration.
- residues within the CDRs of a converted antibody may be additionally substituted with other amino acids.
- residues within the CDRs of a converted antibody may be additionally substituted with other amino acids.
- no more than four amino acid residues in a CDR are changed, and most typically no more than two residues in the CDR will be changed, except for heavy chain CDR 2, where as many as 10 residues may be changed.
- some of the amino acids in the framework sequences may be changed. In all embodiments, no more than 10 amino acid residues are changed
- the humanized antibody sequence is then physically assembled by methods of gene synthesis and recombinant protein expression known by those skilled in the art.
- the final form of the humanized sequences having the chimeric variable chains made by the methods disclosed herein may take many forms. Most typically, the chimeric antibodies will be made by construction a nucleic acid sequence encoding the chimeric variable chains, which are recombinantly expressed in a suitable cell type. One of most typical forms of the chimeric antibody will be an Fab antibody fragment. Other suitable forms of the chimeric antibody include (Fab) 2 molecule, or a single chain Fv molecule. Still other forms may include further fusion to constant domains of a human antibody to form a complete antibody.
- variable light and heavy chains are humanized.
- variable light and heavy chains may be of mixed, i.e., with one fully mouse variable chain (either heavy or light) and the other being a humanized variable chain.
- the method will include screening candidate chimeric antibodies to select those having a dissociation constant for the antigen suitable for an intended use.
- the humanized antibody made according to these methods will have a dissociation constant of at least about 10 6 M "1 , at least about 10 7 M “1 or at least about 10 8 M "1 .
- a Kd of at least about 10 8 M "1 is preferred for most therapeutic uses.
- EXAMPLE 1 HUMANIZED ANTI-CHICKEN LYSOZYME The mouse antibody D1.3 binds to a chicken lysozyme antigen.
- the peptide sequence of the variable domains of D 1.3 were obtained from the Protein Data Bank, accession number 1VFA.
- the light chain was numbered according to Kabat, and the mouse CDRs were assigned canonical structure types as follows:
- Light chain CDRl numbered according to Kabat, consists of the sequence: 24 25 26 27 28 29 30 31 32 33 34 R A S G N I H N Y L A
- CDRl has canonical structure type 2.
- Light chain CDR2 numbered according to Kabat, consists of the sequence: 50 51 52 53 54 55 56 Y T T T L A D
- Light chain CDR3 numbered according to Kabat, consists of the sequence 89 90 91 92 93 94 95 96 97 Q H F W S T P R T Because of the length and the Pro at position 95, this sequence is consistent with canonical structure type 1.
- non- redundant human germline Vk genes encode (1) CDRl with canonical structure type 2, (2) CDR2 with canonical structure type 1, and (3) a sequence with the potential to form canonical structure type 1 at CDR3. These are listed in Figure 3 underneath the D1.3 Vk sequence. Their sequence at the residue positions comprising the Chothia canonical structure types is also given, and the human Vk genes in Figure 3 are stratified according to number of residue-to-residue identities in these sequences. L23 has 7 identities, whereas the next three entries on the list have 6. Furthermore, L23 has conserved residues positions 91 and 92, within CDR3, again superior to the next three candidates. L23 therefore is chosen for the humanizing construction.
- Jk4 which replicates the GGG motif in D1.3 positions 99-101, is the best match for J segment, and is used for the humanizing construction.
- the heavy chain variable domain of D1.3 was numbered according to Kabat, as shown in Figure 4.
- CDRs were assigned canonical structure types as follows.
- the sequence in the region of heavy chain CDRl is 27 28 29 30 31 32 33 34 35
- CDR2 is assigned canonical structure type 1.
- Human germline VH genes predicted to have canonical structure type 1 at CDRl and canonical structure type 1 at CDR2 were taken from Chothia et al (1992) and Figure 1 , and are listed in Figure 4. Segments chosen for homology evaluation were 27 - 35, corresponding to
- JH4 is clearly the best match to the C terminal end of CDR3.
- a chimeric humanized antibody was designed by combining the Kabat CDRs of D 1.3 with the Kabat frameworks encoded by V71-4, JH4, L23, and Jk4. The sequences of the heavy and light chain variable domains of this antibody are shown in Figure 5.
- Synthetic variable domain genes encoding the humanized Vk and VH were prepared from synthetic oligonucleo tides by the method of Ye et al (1992), incorporated herein by reference. These genes were then transferrred to the Fab expression vector pAK19, described by Carter et al (1992), incorporated herein by reference. The DNA sequence of the synthetic genes and of the Fab expression cassette of pAK19 are shown in
- humanized antibody in example 1 has an identical antigenic specificity as the subject mouse antibody, and binds antigen with an affinity diminished by less than a factor of 6 relative to the subject antibody.
- EXAMPLE 2 HUMANIZED ANTI HUMAN CD28
- the mouse anti-human CD28 antibody designated 9.3 was used as the non- human subject antibody.
- the mouse 9.3 hybridoma line was isolated and is described by Hansen et al (1980).
- the heavy and light chain variable region genes of 9.3 were cloned by reverse transcription and the polymerase chain reaction , starting with messenger RNA that had been isolated by a guanidinium isothiocyanate procedure (Chomczynski and Sacchi, 1987) followed by chromatography on oligo-dT columns. Amplification was primed using oligonucleotides complementary to the constant region and oligonucleotides corresponding to regions of the signal peptide or N-terminal framework sequence.
- the light chain was numbered according to Kabat, and CDRs were assigned canonical structures types as follows, with reference to Figure 8.
- Light chain CDRl numbered according to Kabat, consists of the sequence 24 25 26 27 a b c d 28 29 30 31 32 33 34 R A S E S V E Y Y V T S L M Q " Because of the ihs " erted ⁇ resi lues between 27 ⁇ and " 317 " CDP.Thas canonic ⁇ aTstructure type 57
- Light chain CDR2 numbered according to Kabat, consists of the sequence 50 51 52 53 54 55 56 A A S N V E S This is not an exceptional sequence; its canonical structure type is 1.
- Light chain CDR3, numbered according to Kabat, consists of the sequence
- Vk sequences with canonical structure type 5 at CDRl are not represented in the human germline, but structures 3 and 4 resemble canonical structure type 5, and were considered further.
- non-redundant human germline Vk genes encode (1) CDRl with canonical structure type 3 or 4, (2) CDR2 with canonical structure type 1, and (3) a sequence with the potential to form canonical structure type 1 at CDR3. These are listed in Figure 8 underneath the 9.3 Vk sequence. Their sequence at the Kabat CDR is also given.
- the human Vk genes in Figure 3 are ranked according to number of residue-to-residue identities in residue positions forming the Chothia canonical structure.
- the B3 gene has 7 identities in these position, whereas the next three on the list have 5, hence B3 was chosen for the humanizing construction. Had the scoring been based on Kabat CDR positions, rather than Chothia, B3 would still have been the leading candidate.
- the 5'-encoded Tyr residue of human Jk2 matched the corresponding position of 9.3 exactly, hence this germline fragment was used.
- the heavy chain variable domain of 9.3 was numbered according to Kabat, as shown in Figure 9.
- CDRs were assigned canonical structure types as follows. The sequence in the region of heavy chain CDRl is 27 28 29 30 31 32 33 34 35 F S L S D Y G V H ThuTsequence lacks any inserted residues, herice ⁇ is assigned to canonical structure type 1 " .
- the Kabat CDR2 of 9.3 has the sequence
- CDR2 is assigned canonical structure type 1.
- Segments chosen for homology evaluation were 27 - 35, corresponding to Kabat CDRl plus additional residues forming the Chothia canonical structure, and 50 - 60, corresponding to Kabat CDR2 less residues 61 - 65, which seldom participate directly in antigen binding. Sequences were scored for number of identical residues when compared to 9.3, and are ranked by score in Figure 9. Gene DP-45 has the highest number of identities, 10, in a residue-to-residue comparison with 9.3; the next 6 entries all have 9. DP-45 was chosen for the humanizing construction.
- JH4 had the closest homology to the C-terminal end of CDR3 in 9.3, hence was used in the construction.
- Chimeric humanized antibody variable domains were designed by combining sequences as follows.
- the light chain variable domain consisted of Kabat CDR sequences of the 9.3 light chain, with the exception of Residue 34, which was thought to be not critical to antigen recognition, hence was made Ala, identical to the residue in B3 at that position; and framework sequences identical to B3 through residue 88 and identical to Jk2 from positions 98 - 108, with the exception of residues 70 and 72, which were left identical to 9.3 to preserve a glycosylation motif that these residues form in combination with residue 71.
- the heavy chain variable domain consisted of Kabat CDR sequences of the 9.3 heavy chain, with the exception of residues 60 - 65, which were thought to be not critical to antigen recognition and hence made identical to the sequence of DP-45 at those positions; and KabatTramework sequences identical to DP-43 ⁇ fhrough residue 94 " an identical to JH4 from residue 103 - 113.
- FIG. 10 The sequences of the heavy and light chain variable domains of this antibody are shown in Figure 10.
- a recombinant Fab fragment with variable domains these sequences was prepared as described for Example 1, with the exception of using affinity chromatography on Protein-G Sepharose for purification.
- a Fab fragment comprised of mouse 9.3 variable domains and human constant domains was prepared by similar methods, as was a hybrid Fab fragment comprised of human constant domains, mouse 9.3 heavy chain variable domain, and humanized light chain variable domain.
- BCF2 The mouse anti-scorpion toxin antibody designated BCF2 was used as the 10 subject non-human sequence for a humanized anti-scorpion toxin.
- the mouse BCF2 hybridoma line was described, and the efficacy of the BCF2 antibody in a mouse model demonstrated by Licea et al (1996).
- the sequence of the variable domains of BCF2 was disclosed by Selisko et al (1999), and is presented in Figure 12.
- the light chain variable domain consisted of Kabat CDR sequences of the
- the heavy chain variable domain consisted of Kabat CDR sequences of the BCF2 heavy chain, with the exception of residues 62 - 65, which were thought to be not critical to antigen recognition and hence made identical to the sequence of l-f/DP3 at those positions; and Kabat framework
- mice NGAD65 hybridoma line and sequences of its antibody variable domains were described by Hampe et al (2001) and the sequences are presented in Figure 13. The first two residues of the light chain are omitted because they were derived from the oligonucleotide used for cloning.
- Canonical structure types of the light chain CDRs were determined to be type 4 for CDRl, type 1 for CDR2, and type 1 for CDR3.
- Canonical structure types of the heavy chain CDRs were determined to be type 1 for CDRl and type 2 for CDR2.
- the light chain variable domain consisted of Kabat CDR sequences of the NGAD65 light chain; and framework sequences identical to the human Vk gene A17/DPK18 through residue 88 and identical to Jk3 from positions 98 - 108.
- the heavy chain variable domain consisted of Kabat CDR sequences of the BCF2 heavy chain, with the exception of residues 61 - 65, which were thought to be not critical to antigen recognition and hence made identical to the sequence of 1-v at those positions; and Kabat framework sequences identical to l-f/DP3 through residue 94 and identical to JH4 from residue 103 - 113.
- Fab fragment comprised of mouse NGAD65 variable and constant domains was prepared by similar methods.
- Radioactive human glutamic acid decarboxylase was prepared by in vitro translation with 35S-methionine. The labeled antigen was incubated overnight with various concentrations of either of the two Fab fragments. Protein G-Sepharose beads were then added to sequester Fab and any associated antigen. Radioactivity was determined by scintillation counting and the EC50 was determined visually from the midpoint of plots of bound radioactivity versus concentration of Fab fragment. Values of EC50 were obtained of 0.36 pM for the mouse Fab and 9 pM for the humanized Fab.
- humanized antibody Even given the 25-fold loss of affinity of the humanized antibody relative to the mouse antibody, the humanized will still bind antigen sufficiently to be used in human in therapy without need for further mutagenesis of the sequence to make up for the 25 fold loss in affinity.
- the methods provided herein have been exemplified by the use of mouse mature antibody genes as a source of the first Chothia canonical CDR and human antibody genes as a source for the second Chothia canonical CDR. These examples are particularly suitable for the construction of humanized antibodies for use in human therapeutic applications.
- Such humanized antibodies contain sufficient mouse amino sequences to retain a three dimensional structure necessary for avid antigen binding but also contain sufficient human antibody sequences to prevent unwanted immunogenicity in humans.
- the methods disclosed herein are equally applicable to preparing converted antibodies that include chimeric hypervariable regions derived from any two different vertebrate species.
- the first antibody sequence which is originally selected by virtue of its binding to an antigen, may be referred to as the "subject" antibody sequence.
- the subject antibody sequence is of mouse or rat origin.
- the second antibody sequence which is selected from antibody sequences of the target animal, may be 5 referred to as the "object” antibody sequence.
- the object antibody sequence is typically from a human or a farm animal that is the object of therapeutic treatment.
- Antibody compositions containing the chimeric hypervariable regions according to the methods of this invention result in a third antibody sequence which may be generally designated a "converted" antibody sequence.
- the converted antibody sequence differs in certain defined 10 structural features from each of the subject and the object antibody sequences and is identical in certain other defined structural features to each of the subject or object sequences.
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- General Health & Medical Sciences (AREA)
- Biophysics (AREA)
- Biochemistry (AREA)
- Genetics & Genomics (AREA)
- Medicinal Chemistry (AREA)
- Molecular Biology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Life Sciences & Earth Sciences (AREA)
- Peptides Or Proteins (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Description
Claims
Priority Applications (17)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
ES02752269T ES2370225T3 (en) | 2002-07-12 | 2002-07-12 | SUPERHUMANIZED ANTIBODIES. |
US10/194,975 US6881557B2 (en) | 2001-07-12 | 2002-07-12 | Super humanized antibodies |
IL16624402A IL166244A0 (en) | 2001-07-12 | 2002-07-12 | Super humanized antibodies |
MXPA05000511A MXPA05000511A (en) | 2001-07-12 | 2002-07-12 | Super humanized antibodies. |
PCT/US2002/022011 WO2004006955A1 (en) | 2001-07-12 | 2002-07-12 | Super humanized antibodies |
AU2002368077A AU2002368077B2 (en) | 2001-07-12 | 2002-07-12 | Super humanized antibodies |
CN02829598.6A CN1671416B (en) | 2001-07-12 | 2002-07-12 | Super humanized antibodies |
EP10185475A EP2298809A3 (en) | 2001-07-12 | 2002-07-12 | Super humanized antibodies |
DK02752269.7T DK1539233T3 (en) | 2002-07-12 | 2002-07-12 | Humanized super-antibodies |
EP02752269A EP1539233B1 (en) | 2001-07-12 | 2002-07-12 | Super humanized antibodies |
CA2491864A CA2491864C (en) | 2001-07-12 | 2002-07-12 | Super humanized antibodies |
AT02752269T ATE506966T1 (en) | 2002-07-12 | 2002-07-12 | HUMANIZED SUPER ANTIBODIES |
DE60239895T DE60239895D1 (en) | 2002-07-12 | 2002-07-12 | HUMANIZED SUPER ANTIBODIES |
JP2004521391A JP2005538706A (en) | 2001-07-12 | 2002-07-12 | Super humanized antibody |
US11/054,669 US7732578B2 (en) | 2001-07-12 | 2005-02-08 | Super humanized antibodies |
US11/432,734 US7709226B2 (en) | 2001-07-12 | 2006-05-10 | Method of humanizing antibodies by matching canonical structure types CDRs |
US12/749,257 US20110137014A1 (en) | 2001-07-12 | 2010-03-29 | Super humanized antibodies |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US30511101P | 2001-07-12 | 2001-07-12 | |
PCT/US2002/022011 WO2004006955A1 (en) | 2001-07-12 | 2002-07-12 | Super humanized antibodies |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2004006955A1 true WO2004006955A1 (en) | 2004-01-22 |
Family
ID=43602927
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/US2002/022011 WO2004006955A1 (en) | 2001-07-12 | 2002-07-12 | Super humanized antibodies |
Country Status (9)
Country | Link |
---|---|
US (4) | US6881557B2 (en) |
EP (2) | EP1539233B1 (en) |
JP (1) | JP2005538706A (en) |
CN (1) | CN1671416B (en) |
AU (1) | AU2002368077B2 (en) |
CA (1) | CA2491864C (en) |
IL (1) | IL166244A0 (en) |
MX (1) | MXPA05000511A (en) |
WO (1) | WO2004006955A1 (en) |
Cited By (54)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2005112564A2 (en) * | 2004-04-15 | 2005-12-01 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Germline and sequence variants of humanized antibodies and methods of making and using them |
WO2006055778A2 (en) | 2004-11-16 | 2006-05-26 | Kalobios, Inc. | Immunoglobulin variable region cassette exchange |
WO2006096653A2 (en) * | 2005-03-04 | 2006-09-14 | Biogen Idec Ma Inc. | Methods of humanizing immunoglobulin variable regions through rational modification of complementarity determining residues |
WO2007068750A2 (en) | 2005-12-16 | 2007-06-21 | Glaxo Group Limited | Immunoglobulins directed against nogo |
WO2007137984A2 (en) | 2006-05-25 | 2007-12-06 | Glaxo Group Limited | Modified humanised anti-interleukin-18 antibodies |
WO2008017126A1 (en) | 2006-08-11 | 2008-02-14 | Csl Limited | Treatment of pulmonary disease conditions |
JP2009502171A (en) * | 2005-07-25 | 2009-01-29 | トゥルビオン・ファーマシューティカルズ・インコーポレーテッド | Reduction of B cells using CD37-specific and CD20-specific binding molecules |
EP2050765A1 (en) * | 2007-10-19 | 2009-04-22 | Centocor, Inc. | Methods for use in human-adapting monoclonal antibodies |
US7575893B2 (en) | 2003-01-23 | 2009-08-18 | Genentech, Inc. | Methods for producing humanized antibodies and improving yield of antibodies or antigen binding fragments in cell culture |
WO2010070094A1 (en) | 2008-12-19 | 2010-06-24 | Glaxo Group Limited | Myostatin binding proteins |
JP2010533495A (en) * | 2007-07-16 | 2010-10-28 | ジェネンテック, インコーポレイテッド | Humanized CD79b antibodies and immunoconjugates and their use |
US7855276B2 (en) | 2004-12-30 | 2010-12-21 | The United States Of America As Represented By The Department Of Health And Human Services | Framework residue substituted humanized COL-1 antibodies and their use |
WO2011076883A1 (en) | 2009-12-23 | 2011-06-30 | 4-Antibody Ag | Binding members for human cytomegalovirus |
US7981843B2 (en) | 2004-01-20 | 2011-07-19 | Kalobios Pharmaceuticals, Inc. | Antibody specificity transfer using minimal essential binding determinants |
WO2011094259A2 (en) | 2010-01-28 | 2011-08-04 | Glaxo Group Limited | Cd127 binding proteins |
WO2011107480A1 (en) | 2010-03-03 | 2011-09-09 | Glaxo Group Limited | Antigen binding proteins specific for serum amyloid p component |
WO2011151432A1 (en) | 2010-06-03 | 2011-12-08 | Glaxo Group Limited | Humanised antigen binding proteins to myostatin6 |
EP2404935A1 (en) | 2004-03-30 | 2012-01-11 | Glaxo Group Limited | Immunoglobulin binding HOSM |
EP2423229A1 (en) | 2006-03-27 | 2012-02-29 | Medimmune Limited | Binding member for GM-CSF receptor |
WO2012085015A1 (en) | 2010-12-20 | 2012-06-28 | Medimmune Limited | Anti-il-18 antibodies and their uses |
WO2012069433A3 (en) * | 2010-11-23 | 2012-08-09 | Glaxo Group Limited | Antigen binding proteins to oncostatin m (osm) |
US8298533B2 (en) | 2008-11-07 | 2012-10-30 | Medimmune Limited | Antibodies to IL-1R1 |
EP2530090A2 (en) | 2006-10-19 | 2012-12-05 | CSL Limited | Anti-IL-13R alpha 1 antibodies and their uses thereof |
WO2013053767A1 (en) | 2011-10-10 | 2013-04-18 | Medimmune Limited | Treatment for rheumatoid arthritis |
WO2013096380A2 (en) | 2011-12-20 | 2013-06-27 | Janssen Biotech, Inc. | Anti-phf-tau antibodies and their uses |
EP2620452A1 (en) | 2007-02-15 | 2013-07-31 | Medimmune Limited | Binding members for IGE molecules |
EP2628751A2 (en) | 2006-11-30 | 2013-08-21 | AstraZeneca AB | Binding members for interleukin-6 and use thereof |
WO2014006105A1 (en) | 2012-07-05 | 2014-01-09 | Glaxo Group Limited | Optimum dose regime of an anti-nogo-a antibody in the treatment of amyotrophic lateral sclerosis |
WO2014072306A1 (en) | 2012-11-08 | 2014-05-15 | F. Hoffmann-La Roche Ag | Her3 antigen binding proteins binding to the beta-hairpin of her3 |
WO2015179435A1 (en) | 2014-05-19 | 2015-11-26 | Bayer Healthcare Llc | Optimized humanized monoclonal antibodies against activated protein c and uses thereof |
WO2016001140A1 (en) | 2014-06-30 | 2016-01-07 | Affiris Ag | Vaccines and monoclonal antibodies targeting truncated variants of osteopontin and uses thereof |
WO2016059602A2 (en) | 2014-10-16 | 2016-04-21 | Glaxo Group Limited | Methods of treating cancer and related compositions |
WO2016092524A1 (en) | 2014-12-11 | 2016-06-16 | Inbiomotion S.L. | Binding members for human c-maf |
KR20160116056A (en) | 2008-08-14 | 2016-10-06 | 테바 파마슈티컬즈 오스트레일리아 피티와이 엘티디 | Anti-il-12/il-23 antibodies |
WO2017158064A1 (en) | 2016-03-15 | 2017-09-21 | Astrazeneca Ab | Combination of a bace inhibitor and an antibody or antigen-binding fragment for the treatment of a disorder associated with the accumulation of amyloid beta |
US9796788B2 (en) | 2010-02-08 | 2017-10-24 | Regeneron Pharmaceuticals, Inc. | Mice expressing a limited immunoglobulin light chain repertoire |
US9969814B2 (en) | 2010-02-08 | 2018-05-15 | Regeneron Pharmaceuticals, Inc. | Methods for making fully human bispecific antibodies using a common light chain |
WO2018170351A1 (en) | 2017-03-16 | 2018-09-20 | Janssen Biotech, Inc. | Anti-phf-tau antibodies and uses thereof |
US10130081B2 (en) | 2011-08-05 | 2018-11-20 | Regeneron Pharmaceuticals, Inc. | Humanized universal light chain mice |
US10143186B2 (en) | 2010-02-08 | 2018-12-04 | Regeneron Pharmaceuticals, Inc. | Common light chain mouse |
WO2019025299A1 (en) | 2017-07-31 | 2019-02-07 | F. Hoffmann-La Roche Ag | Three-dimensional structure-based humanization method |
US10406197B2 (en) | 2014-07-10 | 2019-09-10 | Affiris Ag | Substances and methods for the use in prevention and/or treatment in Huntington's disease |
US10494432B2 (en) | 2007-07-16 | 2019-12-03 | Genentech, Inc. | Anti-CD79B antibodies and immunoconjugates and methods of use |
US10544218B2 (en) | 2008-01-31 | 2020-01-28 | Genentech, Inc. | Anti-CD79B antibodies and immunoconjugates and methods of use |
EP3434690A4 (en) * | 2016-03-23 | 2020-04-01 | Seoul National University R&DB Foundation | Antibody that binds to envelope glycoprotein of severe fever with thrombocytopenia syndrome virus, and use for same |
US10633435B2 (en) | 2018-03-05 | 2020-04-28 | Janssen Pharmaceutica Nv | Anti-PHF-tau antibodies and uses thereof |
EP3721942A1 (en) | 2012-10-15 | 2020-10-14 | Medimmune Limited | Antibodies to amyloid beta |
US10881085B2 (en) | 2014-03-21 | 2021-01-05 | Regeneron Pharmaceuticals, Inc. | Non-human animals that make single domain binding proteins |
US11000510B2 (en) | 2014-09-23 | 2021-05-11 | Genentech, Inc. | Methods of using anti-CD79b immunoconjugates |
US11111314B2 (en) | 2015-03-19 | 2021-09-07 | Regeneron Pharmaceuticals, Inc. | Non-human animals that select for light chain variable regions that bind antigen |
US11186638B2 (en) | 2011-09-12 | 2021-11-30 | Genzyme Corporation | Anti-αβTCR antibody |
WO2022201122A1 (en) | 2021-03-26 | 2022-09-29 | Janssen Biotech, Inc. | Humanized antibodies against paired helical filament tau and uses thereof |
US11697690B2 (en) | 2014-03-19 | 2023-07-11 | Genzyme Corporation | Site-specific glycoengineering of targeting moieties |
US11807690B2 (en) | 2013-03-11 | 2023-11-07 | Genzyme Corporation | Hyperglycosylated binding polypeptides |
Families Citing this family (413)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7754208B2 (en) | 2001-01-17 | 2010-07-13 | Trubion Pharmaceuticals, Inc. | Binding domain-immunoglobulin fusion proteins |
US20030133939A1 (en) | 2001-01-17 | 2003-07-17 | Genecraft, Inc. | Binding domain-immunoglobulin fusion proteins |
US6881557B2 (en) * | 2001-07-12 | 2005-04-19 | Arrowsmith Technologies Llp | Super humanized antibodies |
ITMI20021527A1 (en) | 2002-07-11 | 2004-01-12 | Consiglio Nazionale Ricerche | C5 COMPONENT ANTIBODIES OF COMPLEMENT AND THEIR USE |
US6875433B2 (en) * | 2002-08-23 | 2005-04-05 | The United States Of America As Represented By The Secretary Of The Army | Monoclonal antibodies and complementarity-determining regions binding to Ebola glycoprotein |
US7388079B2 (en) * | 2002-11-27 | 2008-06-17 | The Regents Of The University Of California | Delivery of pharmaceutical agents via the human insulin receptor |
JP4489077B2 (en) * | 2003-07-15 | 2010-06-23 | アムジェン インコーポレイテッド | Human anti-NGF neutralizing antibodies as selective NGF pathway inhibitors |
CA2533830A1 (en) * | 2003-08-07 | 2005-02-24 | Epitomics, Inc. | Methods for humanizing rabbit monoclonal antibodies |
JP2007528723A (en) * | 2003-08-22 | 2007-10-18 | メディミューン,インコーポレーテッド | Antibody humanization |
US7046714B2 (en) * | 2003-09-10 | 2006-05-16 | Intel Corporation | Method and apparatus for Raman ring resonator based laser/wavelength converter |
EA202091901A1 (en) * | 2003-11-05 | 2020-11-24 | Роше Гликарт Аг | ANTIBODIES WITH INCREASED AFFINITY TO BINDING WITH THE Fc-RECEPTOR AND EFFECTORAL FUNCTION |
JP2007534307A (en) * | 2003-11-07 | 2007-11-29 | キュラジェン コーポレイション | Antibodies against secretory leukocyte protease inhibitors |
PE20090046A1 (en) | 2003-11-10 | 2009-01-26 | Schering Corp | RECOMBINANT ANTI-INTERLEUQUIN HUMANIZED ANTIBODY 10 |
EP1720908A2 (en) * | 2004-02-17 | 2006-11-15 | Absalus, Inc. | Super-humanized antibodies against respiratory syncytial virus |
JP5128935B2 (en) * | 2004-03-31 | 2013-01-23 | ジェネンテック, インコーポレイテッド | Humanized anti-TGF-β antibody |
ME00226B (en) | 2004-07-15 | 2011-02-10 | Medarex Llc | Human anti-ngf neutralizing antibodies as selective ngf pathway inhibitors |
WO2006029459A1 (en) * | 2004-09-13 | 2006-03-23 | Evogenix, Inc | Antibodies specific for hepatocellular carcinoma and other carcinomas and uses thereof |
JP2008513372A (en) * | 2004-09-13 | 2008-05-01 | アロースミス テクノロジーズ エルエルピー | Antibody buffering of ligands in vivo |
WO2006082515A2 (en) | 2005-02-07 | 2006-08-10 | Glycart Biotechnology Ag | Antigen binding molecules that bind egfr, vectors encoding same, and uses thereof |
AU2006226060A1 (en) * | 2005-03-25 | 2006-09-28 | Glycart Biotechnology Ag | Antigen binding molecules directed to MCSP and having increased Fc receptor binding affinity and effector function |
EP1888649A2 (en) * | 2005-05-09 | 2008-02-20 | GlycArt Biotechnology AG | Antigen binding molecules having modified fc regions and altered binding to fc receptors |
BRPI0613361A2 (en) | 2005-07-01 | 2011-01-04 | Medarex Inc | isolated human monoclonal antibody, composition, immunoconjugate, bispecific molecule, isolated nucleic acid molecule, expression vector, host cell, transgenic mouse, method for modulating an immune response in an individual, method for inhibiting tumor cell growth in an individual, method for treating an infectious disease in a subject, a method for enhancing an immune response to an antigen in a subject, a method for treating or preventing an inflammatory disease in a subject, and a method for preparing the anti-pd-11 antibody |
AU2006281980A1 (en) * | 2005-08-15 | 2007-02-22 | Cephalon Australia Pty Ltd | Engineered antibodies with new world primate framework regions |
CN101291954B (en) * | 2005-08-26 | 2013-03-27 | 罗氏格黎卡特股份公司 | Modified antigen binding molecules with altered cell signaling activity |
AU2006326937B2 (en) * | 2005-12-20 | 2012-01-19 | Cephalon Australia Pty Ltd | Anti-inflammatory dAb |
EP1987064A4 (en) * | 2006-02-01 | 2010-04-07 | Arana Therapeutics Ltd | Domain antibody construct |
SG158112A1 (en) | 2006-06-02 | 2010-01-29 | Aveo Pharmaceuticals Inc | Hepatocyte growth factor (hgf) binding proteins |
EP2029627B1 (en) * | 2006-06-02 | 2011-11-16 | Aveo Pharmaceuticals, Inc. | Hepatocyte growth factor (hgf) binding proteins |
SG172698A1 (en) * | 2006-06-12 | 2011-07-28 | Trubion Pharmaceuticals Inc | Single-chain multivalent binding proteins with effector function |
AR062223A1 (en) * | 2006-08-09 | 2008-10-22 | Glycart Biotechnology Ag | MOLECULES OF ADHESION TO THE ANTIGEN THAT ADHER TO EGFR, VECTORS THAT CODE THEM, AND THEIR USES OF THESE |
CL2007002567A1 (en) | 2006-09-08 | 2008-02-01 | Amgen Inc | ISOLATED PROTEINS FROM LINK TO ACTIVINE TO HUMAN. |
EP2094728B1 (en) * | 2006-10-26 | 2013-04-10 | Janssen Biotech, Inc. | Methods for use in human-adapting monoclonal antibodies |
KR101552735B1 (en) * | 2006-12-01 | 2015-09-14 | 메다렉스, 엘.엘.시. | 22 human antibodies that bind cd22 and uses thereof |
US20080139790A1 (en) * | 2006-12-08 | 2008-06-12 | Jennings Philip A | Chimeric antibodies |
WO2008076487A2 (en) | 2006-12-20 | 2008-06-26 | Verenium Corporation | Antibodies and methods for making and using them |
US20100291024A1 (en) * | 2007-03-30 | 2010-11-18 | Xuebin Qin | Methods and compositions for the treatment of proliferative and pathogenic diseases |
WO2008137066A1 (en) * | 2007-05-02 | 2008-11-13 | The Board Of Regents Of The University Of Oklahoma | Use of compacted nucleic acid nanoparticles in non-viral treatments of ocular diseases |
WO2008154439A1 (en) * | 2007-06-08 | 2008-12-18 | Irm Llc | Methods and compositions for inducing apoptosis in cancer cells |
US7982016B2 (en) | 2007-09-10 | 2011-07-19 | Amgen Inc. | Antigen binding proteins capable of binding thymic stromal lymphopoietin |
WO2009072660A1 (en) * | 2007-12-03 | 2009-06-11 | Kabushiki Kaisya Advance | Method for production of antibody |
AR070141A1 (en) * | 2008-01-23 | 2010-03-17 | Glenmark Pharmaceuticals Sa | SPECIFIC HUMANIZED ANTIBODIES FOR VON WILLEBRAND FACTOR |
RS51975B (en) | 2008-04-11 | 2012-02-29 | Emergent Product Development Seattle Llc. | Cd37 immunotherapeutic and combination with bifunctionalchemotherapeutic thereof |
WO2010021874A2 (en) * | 2008-08-20 | 2010-02-25 | Centocor Ortho Biotech Inc. | Engineered anti-il-13 antibodies, compositions, methods and uses |
DK2346994T3 (en) | 2008-09-30 | 2022-02-28 | Ablexis Llc | Knock-in mice for the production of chimeric antibodies |
JP2012505654A (en) * | 2008-10-14 | 2012-03-08 | ヤンセン バイオテツク,インコーポレーテツド | Methods for humanizing and affinity maturating antibodies |
DK2365828T3 (en) | 2008-11-07 | 2014-12-08 | Galaxy Biotech Llc | Monoclonal antibodies against fibroblast second |
NZ620326A (en) * | 2008-11-13 | 2015-07-31 | Emergent Product Dev Seattle | Cd37 immunotherapeutic combination therapies and uses thereof |
BRPI1009460A2 (en) * | 2009-03-16 | 2016-03-01 | Cephalon Australia Pty Ltd | antibody binding domain, antibody, use of a binding domain or antibody, method for detecting the presence of cancer cells in a sample. |
US8221753B2 (en) | 2009-09-30 | 2012-07-17 | Tracon Pharmaceuticals, Inc. | Endoglin antibodies |
WO2011022472A2 (en) * | 2009-08-18 | 2011-02-24 | President And Fellows Of Harvard College | Methods and compositions for the treatment of proliferative and pathogenic diseases |
WO2011054030A1 (en) * | 2009-11-05 | 2011-05-12 | Cephalon Australia Pty Ltd | Treatment of cancer involving mutated kras or braf genes |
EA034462B1 (en) | 2009-11-24 | 2020-02-11 | Алетиа Байотерапьютикс Инк. | Anti-clusterin antibodies and antigen binding fragments and their use to reduce tumor volume |
PL2954779T3 (en) | 2009-12-10 | 2019-07-31 | Regeneron Pharmaceuticals, Inc. | Mice that make heavy chain antibodies |
US8765432B2 (en) | 2009-12-18 | 2014-07-01 | Oligasis, Llc | Targeted drug phosphorylcholine polymer conjugates |
US20120021409A1 (en) * | 2010-02-08 | 2012-01-26 | Regeneron Pharmaceuticals, Inc. | Common Light Chain Mouse |
US9011861B2 (en) * | 2010-02-25 | 2015-04-21 | Schepens Eye Research Institute | Therapeutic compositions for the treatment of dry eye disease |
AU2011234988B2 (en) * | 2010-03-31 | 2014-10-30 | Ablexis, Llc | Genetic engineering of non-human animals for the production of chimeric antibodies |
KR20130010123A (en) * | 2010-04-07 | 2013-01-25 | 아비에 인코포레이티드 | TNF-α BINDING PROTEINS |
WO2011127324A2 (en) | 2010-04-08 | 2011-10-13 | JN Biosciences, LLC | Antibodies to cd122 |
BR112012025730B1 (en) | 2010-04-09 | 2020-12-08 | Aveo Pharmaceuticals, Inc | isolated antibody that binds to human erbb3, its uses, its production process and expression vector |
WO2011156617A2 (en) | 2010-06-09 | 2011-12-15 | Aveo Pharmaceuticals, Inc. | Anti-egfr antibodies |
WO2012003472A1 (en) | 2010-07-02 | 2012-01-05 | Aveo Pharmaceuticals, Inc. | Anti-notch1 antibodies |
JP2013533746A (en) | 2010-07-06 | 2013-08-29 | アベオ ファーマシューティカルズ, インコーポレイテッド | Anti-RON antibody |
EP2596022A4 (en) | 2010-07-20 | 2014-11-05 | Cephalon Australia Pty Ltd | Anti-il-23 heterodimer specific antibodies |
NZ604510A (en) | 2010-08-17 | 2013-10-25 | Csl Ltd | Dilutable biocidal compositions and methods of use |
US10865445B2 (en) | 2010-08-18 | 2020-12-15 | Fred Hutchinson Cancer Research Center | Methods for alleviating facioscapulohumeral dystrophy (FSHD) by N siRNA molecule inhibiting the expression of DUX4-FL |
NZ611468A (en) | 2010-12-06 | 2015-06-26 | Seattle Genetics Inc | Humanized antibodies to liv-1 and use of same to treat cancer |
EP2654790B1 (en) | 2010-12-22 | 2019-02-06 | Teva Pharmaceuticals Australia Pty Ltd | Modified antibody with improved half-life |
JOP20210044A1 (en) | 2010-12-30 | 2017-06-16 | Takeda Pharmaceuticals Co | Anti-cd38 antibodies |
ES2899186T3 (en) * | 2010-12-31 | 2022-03-10 | Bioatla Inc | Rapid antibody humanization |
EP3252076B1 (en) | 2011-01-14 | 2019-09-04 | The Regents Of The University Of California | Diagnostic use of antibodies against ror-1 protein |
EP2668210B1 (en) | 2011-01-26 | 2020-06-17 | Celldex Therapeutics, Inc. | Anti-kit antibodies and uses thereof |
CN105968209B (en) | 2011-04-19 | 2021-08-03 | 美国政府(由卫生和人类服务部的部长所代表) | Human monoclonal antibodies specific for glypican 3 and uses thereof |
WO2012175735A1 (en) | 2011-06-23 | 2012-12-27 | Vib Vzw | A20 inhibitors for the treatment of respiratory viral infections |
HUE039009T2 (en) | 2011-08-05 | 2018-12-28 | Res Found Dev | Improved methods and compositions for modulation of olfml3 mediated angiogenesis |
GB201116092D0 (en) | 2011-09-16 | 2011-11-02 | Bioceros B V | Antibodies and uses thereof |
WO2013044298A1 (en) | 2011-09-30 | 2013-04-04 | Cephalon Australia Pty Ltd | Antibodies against tl1a and uses thereof |
LT3378535T (en) | 2011-10-28 | 2023-02-27 | Prothena Biosciences Limited | Humanized antibodies that recognize alpha-synuclein |
AU2012327878A1 (en) | 2011-10-28 | 2014-05-29 | Patrys Limited | PAT-LM1 epitopes and methods for using same |
SG10201603411WA (en) | 2011-10-28 | 2016-07-28 | Teva Pharmaceuticals Australia Pty Ltd | Polypeptide constructs and uses thereof |
WO2013092983A2 (en) | 2011-12-23 | 2013-06-27 | Innate Pharma | Enzymatic conjugation of polypeptides |
CN104411717A (en) | 2012-01-09 | 2015-03-11 | 斯克利普斯研究所 | Humanized antibodies with ultralong CDR3S |
RU2642262C2 (en) | 2012-01-27 | 2018-01-24 | Протена Биосайенсис Лимитед | Humanized antibodies, which recognize alpha-sinuclein |
US9546219B2 (en) | 2012-02-08 | 2017-01-17 | North Carolina State University | Treatment of allergic diseases with recombinant antibodies |
WO2013125221A1 (en) * | 2012-02-21 | 2013-08-29 | 静岡県 | Affinity ligand for antibody purification |
BR112014020756A2 (en) | 2012-02-22 | 2017-07-04 | Alethia Biotherapeutics Inc | co-use of a clusterin inhibitor with an egfr inhibitor to treat cancer |
EP2847219A1 (en) | 2012-05-07 | 2015-03-18 | Amgen Inc. | Anti-erythropoietin antibodies |
US20130309223A1 (en) | 2012-05-18 | 2013-11-21 | Seattle Genetics, Inc. | CD33 Antibodies And Use Of Same To Treat Cancer |
EP2854523A1 (en) * | 2012-06-05 | 2015-04-08 | Regeneron Pharmaceuticals, Inc. | Methods for making fully human bispecific antibodies using a common light chain |
WO2014004549A2 (en) | 2012-06-27 | 2014-01-03 | Amgen Inc. | Anti-mesothelin binding proteins |
WO2014009426A2 (en) | 2012-07-13 | 2014-01-16 | Innate Pharma | Screening of conjugated antibodies |
WO2014018625A1 (en) | 2012-07-25 | 2014-01-30 | Kolltan Pharmaceuticals, Inc. | Anti-kit antibodies and uses thereof |
UA115789C2 (en) | 2012-09-05 | 2017-12-26 | Трейкон Фармасутікалз, Інк. | Antibody formulations and uses thereof |
UA118441C2 (en) | 2012-10-08 | 2019-01-25 | Протена Біосаєнсиз Лімітед | Antibodies recognizing alpha-synuclein |
CA2888345C (en) | 2012-10-24 | 2020-04-21 | Research Development Foundation | Jam-c antibodies and methods for treatment of cancer |
EP2912194B1 (en) | 2012-10-26 | 2019-05-08 | Memorial Sloan-Kettering Cancer Center | Androgen receptor variants and methods for making and using |
WO2014072482A1 (en) | 2012-11-09 | 2014-05-15 | Innate Pharma | Recognition tags for tgase-mediated conjugation |
EP2935330B1 (en) | 2012-12-19 | 2019-04-24 | Aveo Pharmaceuticals, Inc. | Anti-notch3 antibodies |
AR094271A1 (en) | 2012-12-21 | 2015-07-22 | Aveo Pharmaceuticals Inc | ANTI-BODY ANTIBODIES |
JP6502856B2 (en) | 2012-12-26 | 2019-04-17 | オンコシナジー インコーポレイテッド | Anti-integrin beta 1 antibody composition and method of using the same |
SG11201505960VA (en) | 2013-02-01 | 2015-08-28 | Santa Maria Biotherapeutics Inc | Administration of an anti-activin-a compound to a subject |
AU2014213009B2 (en) | 2013-02-01 | 2019-01-03 | Kira Biotech Pty Limited | Anti-CD83 antibodies and use thereof |
DK2953971T3 (en) | 2013-02-07 | 2023-05-01 | Csl Ltd | IL-11R BINDING PROTEINS AND USES THEREOF |
EP3888671A3 (en) | 2013-03-11 | 2022-01-05 | Amgen Inc. | Protein formulations |
CN105121465B (en) | 2013-03-13 | 2020-09-08 | 普罗塞纳生物科技公司 | TAU immunotherapy |
EP2968582B1 (en) | 2013-03-15 | 2020-07-01 | Innate Pharma | Solid phase tgase-mediated conjugation of antibodies |
EP2970483A2 (en) | 2013-03-15 | 2016-01-20 | Amgen Inc. | Methods and compositions relating to anti-ccr7 antigen binding proteins |
US9695245B2 (en) | 2013-03-15 | 2017-07-04 | Edimer Pharmaceuticals, Inc | Anti-ectodysplasin antibodies |
CN105229032A (en) | 2013-03-18 | 2016-01-06 | 比奥塞罗克斯产品公司 | The anti-CD134 of humanization (OX40) antibody and application thereof |
CA2909952C (en) | 2013-04-29 | 2021-10-12 | Teva Pharmaceuticals Australia Pty Ltd. | Anti-cd38 antibodies and fusions to attenuated interferon alpha-2b |
US11117975B2 (en) | 2013-04-29 | 2021-09-14 | Teva Pharmaceuticals Australia Pty Ltd | Anti-CD38 antibodies and fusions to attenuated interferon alpha-2B |
US10071169B2 (en) | 2013-06-20 | 2018-09-11 | Innate Pharma | Enzymatic conjugation of polypeptides |
EP3010548A1 (en) | 2013-06-21 | 2016-04-27 | Innate Pharma | Enzymatic conjugation of polypeptides |
EP3013361B1 (en) * | 2013-06-24 | 2021-10-06 | NexImmune, Inc. | Compositions and methods for immunotherapy |
US10513555B2 (en) | 2013-07-04 | 2019-12-24 | Prothena Biosciences Limited | Antibody formulations and methods |
US9850302B2 (en) | 2013-07-12 | 2017-12-26 | Prothena Biosciences Limited | Antibodies that recognize IAPP |
US9951131B2 (en) | 2013-07-12 | 2018-04-24 | Prothena Biosciences Limited | Antibodies that recognize IAPP |
CN111518199A (en) * | 2013-07-18 | 2020-08-11 | 图鲁斯生物科学有限责任公司 | Humanized antibodies with ultralong complementarity determining regions |
WO2015027120A1 (en) | 2013-08-21 | 2015-02-26 | Jiang Jean X | Compositions and methods for targeting connexin hemichannels |
ES2819217T3 (en) | 2013-09-08 | 2021-04-15 | Kodiak Sciences Inc | Conjugates of zwitterionic polymers and factor VIII |
LT3065774T (en) | 2013-11-06 | 2021-09-10 | Janssen Biotech, Inc. | Anti-ccl17 antibodies |
EP3071974A2 (en) | 2013-11-19 | 2016-09-28 | Prothena Biosciences Limited | Monitoring immunotherapy of lewy body disease from constipation symptoms |
AU2014354588B2 (en) | 2013-11-28 | 2020-07-02 | B-Creative Sweden Ab | Method of treating nephropathy |
US9321834B2 (en) | 2013-12-05 | 2016-04-26 | Leidos, Inc. | Anti-malarial compositions |
WO2015089338A2 (en) | 2013-12-11 | 2015-06-18 | Sloan-Kettering Institute For Cancer Research | Glucocorticoid inhibitors for treatment of prostate cancer |
PL3082860T3 (en) | 2013-12-18 | 2021-06-14 | Csl Limited | Method of treating wounds |
EP3116907A1 (en) | 2014-03-12 | 2017-01-18 | Prothena Biosciences Limited | Anti-laminin4 antibodies specific for lg4-5 |
DK3116911T3 (en) | 2014-03-12 | 2019-09-30 | Prothena Biosciences Ltd | ANTI-MCAM ANTIBODIES AND RELATED PROCEDURES FOR USE |
TW201623331A (en) | 2014-03-12 | 2016-07-01 | 普羅帝納生物科學公司 | Anti-MCAM antibodies and associated methods of use |
WO2015136471A1 (en) | 2014-03-12 | 2015-09-17 | Prothena Biosciences Limited | Anti-laminin4 antibodies specific for lg1-3 |
EP3116910A1 (en) | 2014-03-13 | 2017-01-18 | Prothena Biosciences Limited | Combination treatment for multiple sclerosis |
US10562973B2 (en) | 2014-04-08 | 2020-02-18 | Prothena Bioscience Limited | Blood-brain barrier shuttles containing antibodies recognizing alpha-synuclein |
US10087259B1 (en) | 2014-04-28 | 2018-10-02 | Memorial Sloan Kettering Cancer Center | Depleting tumor-specific tregs |
UA119352C2 (en) | 2014-05-01 | 2019-06-10 | Тева Фармасьютикалз Острейліа Пті Лтд | Combination of lenalidomide or pomalidomide and cd38 antibody-attenuated interferon-alpha constructs, and the use thereof |
IL293212B2 (en) | 2014-05-28 | 2023-12-01 | Memorial Sloan Kettering Cancer Center | Anti–gitr antibodies and methods of use thereof |
WO2015196142A1 (en) | 2014-06-20 | 2015-12-23 | Aveo Pharmaceuticals, Inc. | Treatment of congestive heart failure and other cardiac dysfunction using a gdf15 modulator |
AU2015276800B2 (en) | 2014-06-20 | 2021-03-04 | Aveo Pharmaceuticals, Inc. | Treatment of chronic kidney disease and other renal dysfunction using a GDF15 modulator |
TWI713453B (en) | 2014-06-23 | 2020-12-21 | 美商健生生物科技公司 | Interferon alpha and omega antibody antagonists |
US9840553B2 (en) | 2014-06-28 | 2017-12-12 | Kodiak Sciences Inc. | Dual PDGF/VEGF antagonists |
EP3166688B1 (en) | 2014-07-08 | 2024-08-21 | New York University | Tau imaging ligands and their uses in the diagnosis and treatment of tauopathy |
US20160075772A1 (en) | 2014-09-12 | 2016-03-17 | Regeneron Pharmaceuticals, Inc. | Treatment of Fibrodysplasia Ossificans Progressiva |
CA2961917A1 (en) | 2014-09-22 | 2016-03-31 | Intrinsic Lifesciences Llc | Humanized anti-hepcidin antibodies and uses thereof |
EP3197493B1 (en) | 2014-09-25 | 2021-03-10 | Aveo Pharmaceuticals Inc. | Methods of reversing cachexia and prolonging survival comprising administering a gdf15 modulator and an anti-cancer agent |
EP3207128B1 (en) | 2014-10-17 | 2022-07-27 | Kodiak Sciences Inc. | Butyrylcholinesterase zwitterionic polymer conjugates |
WO2016061617A1 (en) | 2014-10-23 | 2016-04-28 | Dendrocyte Biotech Pty Ltd | Cd83 binding proteins and uses thereof |
WO2016062734A1 (en) * | 2014-10-24 | 2016-04-28 | F. Hoffmann-La Roche Ag | Vh-vl-interdomain angle based antibody humanization |
JP6730271B2 (en) | 2014-10-29 | 2020-07-29 | テバ・ファーマシューティカルズ・オーストラリア・ピーティワイ・リミテッド | Interferon α2B variant |
US9926375B2 (en) | 2014-11-12 | 2018-03-27 | Tracon Pharmaceuticals, Inc. | Anti-endoglin antibodies and uses thereof |
US10155820B2 (en) | 2014-11-12 | 2018-12-18 | Tracon Pharmaceuticals, Inc. | Anti-endoglin antibodies and uses thereof |
ES2717308T3 (en) | 2014-12-06 | 2019-06-20 | Gemoab Monoclonals Gmbh | Pluri- or multi-potent genetically modified stem cells and their uses |
EP3233120A4 (en) | 2014-12-19 | 2018-05-30 | Monash University | Il-21 antibodies |
AU2015371265B2 (en) | 2014-12-24 | 2021-06-03 | Neximmune, Inc | Nanoparticle compositions and methods for immunotherapy |
EA037654B1 (en) | 2014-12-30 | 2021-04-27 | Селджин Корпорейшн | Anti-cd47 antibodies and uses thereof |
TWI718121B (en) | 2015-01-28 | 2021-02-11 | 愛爾蘭商普羅佘納生物科技有限公司 | Anti-transthyretin antibodies |
TWI718122B (en) | 2015-01-28 | 2021-02-11 | 愛爾蘭商普羅佘納生物科技有限公司 | Anti-transthyretin antibodies |
TWI711631B (en) | 2015-01-28 | 2020-12-01 | 愛爾蘭商普羅佘納生物科技有限公司 | Anti-transthyretin antibodies |
ES2929614T3 (en) | 2015-03-17 | 2022-11-30 | Memorial Sloan Kettering Cancer Center | Anti-MUC16 antibodies and uses thereof |
JP6892826B2 (en) | 2015-03-18 | 2021-06-23 | シージェン インコーポレイテッド | CD48 antibody and its complex |
CA2981312C (en) | 2015-03-30 | 2023-09-26 | Regeneron Pharmaceuticals, Inc. | Heavy chain constant regions with reduced binding to fc gamma receptors |
AU2016253149B2 (en) | 2015-04-24 | 2022-05-19 | The Regents Of The University Of California | Modulators of ROR1-ROR2 binding |
KR20170140318A (en) | 2015-04-29 | 2017-12-20 | 리제너론 파마슈티칼스 인코포레이티드 | Treatment of advanced ossificant fibrous dysplasia |
CN115109158A (en) | 2015-05-07 | 2022-09-27 | 阿吉纳斯公司 | anti-OX 40 antibodies and methods of use thereof |
DK3447075T3 (en) | 2015-05-15 | 2023-11-13 | Massachusetts Gen Hospital | Antagonistic antibodies of the antitumor necrosis factor receptor superfamily |
SI3303394T1 (en) | 2015-05-29 | 2020-10-30 | Agenus Inc. | Anti-ctla-4 antibodies and methods of use thereof |
TW201709932A (en) | 2015-06-12 | 2017-03-16 | 西雅圖遺傳學公司 | CD123 antibodies and conjugates thereof |
MX2017017049A (en) | 2015-06-30 | 2018-03-06 | Seattle Genetics Inc | Anti-ntb-a antibodies and related compositions and methods. |
GB201512203D0 (en) | 2015-07-13 | 2015-08-19 | Lundbeck & Co As H | Agents,uses and methods |
GB201512215D0 (en) | 2015-07-13 | 2015-08-19 | Lundbeck & Co As H | Agents,uses and methods |
JO3711B1 (en) | 2015-07-13 | 2021-01-31 | H Lundbeck As | Antibodies specific for hyperphosphorylated tau and methods of use thereof |
CN114605549A (en) | 2015-08-05 | 2022-06-10 | 詹森生物科技公司 | anti-CD 154 antibodies and methods of use thereof |
CN108135986B (en) | 2015-08-13 | 2022-07-29 | 纽约大学 | Antibody-based molecules specific for a truncated Asp421 epitope of Tau and their use in the diagnosis and treatment of Tau disease |
CN108137679B (en) | 2015-08-13 | 2022-07-19 | 纽约大学 | For Tau, of{p}Antibody-based molecules selective for the Ser404 epitope and their use in the diagnosis and treatment of Tau disease |
KR102434314B1 (en) | 2015-09-01 | 2022-08-19 | 아게누스 인코포레이티드 | Anti-PD-1 antibodies and methods of using them |
EP4223784A3 (en) | 2015-09-02 | 2023-10-04 | The Regents of the University of Colorado, a body corporate | Compositions and methods for modulating t-cell mediated immune response |
WO2017048902A1 (en) | 2015-09-15 | 2017-03-23 | Board Of Regents, The University Of Texas System | T-cell receptor (tcr)-binding antibodies and uses thereof |
JP2018530540A (en) | 2015-09-16 | 2018-10-18 | プロセナ バイオサイエンシーズ リミテッド | Use of anti-MCAM antibodies for the treatment or prevention of giant cell arteritis, polymyalgia rheumatica or Takayasu arteritis |
WO2017046774A2 (en) | 2015-09-16 | 2017-03-23 | Prothena Biosciences Limited | Use of anti-mcam antibodies for treatment or prophylaxis of giant cell arteritis, polymyalgia rheumatica or takayasu's arteritis |
UA126278C2 (en) | 2015-09-21 | 2022-09-14 | Аптево Рісьорч Енд Девелопмент Ллс | Cd3 binding polypeptides |
CA2997444A1 (en) | 2015-09-29 | 2017-04-06 | Amgen Inc. | Asgr inhibitors for reducing cholesterol levels |
JP6869553B2 (en) | 2015-10-30 | 2021-05-12 | ギャラクシー バイオテック, エルエルシーGalaxy Biotech, Llc | Very strong antibody that binds to death receptor 4 and death receptor 5. |
EP4046655A1 (en) | 2015-11-03 | 2022-08-24 | Janssen Biotech, Inc. | Antibodies specifically binding pd-1 and their uses |
EP3383908A1 (en) | 2015-12-02 | 2018-10-10 | Stsciences, Inc. | Antibodies specific to glycosylated btla (b- and t- lymphocyte attenuator) |
US20180355043A1 (en) | 2015-12-17 | 2018-12-13 | Janssen Biotech, Inc. | Antibodies Specifically Binding HLA-DR and Their Uses |
RU2744860C2 (en) | 2015-12-30 | 2021-03-16 | Кодиак Сайенсиз Инк. | Antibodies and their conjugates |
JP7161938B2 (en) | 2016-01-10 | 2022-10-27 | ネオティーエックス セラピューティクス リミテッド | Methods and compositions for enhancing the potency of superantigen-mediated cancer immunotherapy |
MA44254A (en) | 2016-02-17 | 2018-12-26 | Seattle Genetics Inc | BCMA ANTIBODIES AND THEIR USE TO TREAT CANCER AND IMMUNOLOGICAL DISORDERS |
JP7098527B2 (en) | 2016-02-26 | 2022-07-11 | ザ ボード オブ リージェンツ オブ ザ ユニバーシティー オブ テキサス システム | Connexin (Cx) 43 hemichannel-binding antibody and its use |
WO2017149513A1 (en) | 2016-03-03 | 2017-09-08 | Prothena Biosciences Limited | Anti-mcam antibodies and associated methods of use |
CA3014934A1 (en) | 2016-03-04 | 2017-09-08 | JN Biosciences, LLC | Antibodies to tigit |
WO2017153955A1 (en) | 2016-03-09 | 2017-09-14 | Prothena Biosciences Limited | Use of anti-mcam antibodies for treatment or prophylaxis of granulomatous lung diseases |
WO2017153953A1 (en) | 2016-03-09 | 2017-09-14 | Prothena Biosciences Limited | Use of anti-mcam antibodies for treatment or prophylaxis of granulomatous lung diseases |
JP7080213B2 (en) | 2016-03-23 | 2022-06-03 | スーチョウ トランセンタ セラピューティクス カンパニー,リミテッド | New anti-PD-L1 antibody |
KR20230031373A (en) | 2016-03-29 | 2023-03-07 | 주식회사 에스티큐브앤컴퍼니 | Methods for selecting antibodies that specifically bind glycosylated immune checkpoint proteins |
US11660352B2 (en) | 2016-03-29 | 2023-05-30 | Stcube, Inc. | Dual function antibodies specific to glycosylated PD-L1 and methods of use thereof |
RS63735B1 (en) | 2016-04-01 | 2022-12-30 | Kite Pharma Inc | Chimeric receptors and methods of use thereof |
TWI795133B (en) | 2016-04-01 | 2023-03-01 | 美商凱特製藥公司 | Bcma binding molecules and uses thereof |
CR20180461A (en) | 2016-04-01 | 2019-03-05 | Kite Pharma Inc | RECEIVERS OF CHEMICAL ANTIGENS AND T-CELLS AND METHODS OF USE |
US11016085B2 (en) | 2016-04-25 | 2021-05-25 | The Johns Hopkins University | ZNT8 assays for drug development and pharmaceutical compositions |
PT3452507T (en) | 2016-05-02 | 2022-12-20 | Prothena Biosciences Ltd | Tau immunotherapy |
BR112018072394A2 (en) | 2016-05-02 | 2019-02-19 | Prothena Biosciences Limited | antibodies that recognize the tau |
KR102471787B1 (en) | 2016-05-02 | 2022-11-29 | 프로테나 바이오사이언시즈 리미티드 | Tau recognition antibody |
EP3464360A1 (en) | 2016-05-27 | 2019-04-10 | Agenus Inc. | Anti-tim-3 antibodies and methods of use thereof |
MY194619A (en) | 2016-06-02 | 2022-12-07 | Abbvie Inc | Glucocorticoid receptor agonist and immunoconjugates thereof |
WO2017208210A1 (en) | 2016-06-03 | 2017-12-07 | Prothena Biosciences Limited | Anti-mcam antibodies and associated methods of use |
EP3464374A2 (en) | 2016-06-06 | 2019-04-10 | City of Hope | Baff-r antibodies and uses thereof |
AU2017277269B2 (en) | 2016-06-06 | 2024-03-28 | Board Of Regents, The University Of Texas System | BAFF-R targeted chimeric antigen receptor-modified T-cells and uses thereof |
WO2018007923A2 (en) | 2016-07-02 | 2018-01-11 | Prothena Biosciences Limited | Anti-transthyretin antibodies |
WO2018007924A2 (en) | 2016-07-02 | 2018-01-11 | Prothena Biosciences Limited | Anti-transthyretin antibodies |
WO2018007922A2 (en) | 2016-07-02 | 2018-01-11 | Prothena Biosciences Limited | Anti-transthyretin antibodies |
US11427632B2 (en) | 2016-07-06 | 2022-08-30 | Celgene Corporation | Antibodies with low immunogenicity and uses thereof |
AU2017292184A1 (en) | 2016-07-08 | 2019-02-07 | Staten Biotechnology B.V. | Anti-Apoc3 antibodies and methods of use thereof |
EP3481869A4 (en) | 2016-07-11 | 2020-02-26 | Corvus Pharmaceuticals, Inc. | Anti-cd73 antibodies |
MY197836A (en) | 2016-07-12 | 2023-07-20 | H Lundbeck As | Antibodies specific for hyperphosphorylated tau and methods of use thereof |
KR102223822B1 (en) | 2016-07-12 | 2021-03-11 | 카이트 파마 인코포레이티드 | Antigen-binding molecule and method of use thereof |
CN110087673A (en) | 2016-07-19 | 2019-08-02 | 梯瓦制药澳大利亚股份有限公司 | Anti- CD47 combination therapy |
US11746152B2 (en) | 2016-07-20 | 2023-09-05 | Stcube, Inc. | Methods of cancer treatment and therapy using a combination of antibodies that bind glycosylated PD-L1 |
US11878060B2 (en) | 2016-08-07 | 2024-01-23 | Novartis Ag | mRNA-mediated immunization methods |
US20180044430A1 (en) | 2016-08-12 | 2018-02-15 | Janssen Biotech, Inc. | FC Engineered Anti-TNFR Superfamily Member Antibodies Having Enhanced Atonistic Activity and Methods of Using Them |
US10669344B2 (en) | 2016-08-12 | 2020-06-02 | Janssen Biotech, Inc. | Engineered antibodies and other Fc-domain containing molecules with enhanced agonism and effector functions |
CA3034105A1 (en) | 2016-09-23 | 2018-03-29 | Csl Limited | Coagulation factor binding proteins and uses thereof |
TWI719894B (en) | 2016-09-28 | 2021-02-21 | 美商凱特製藥公司 | Antigen binding molecules and methods of use thereof |
CN117586403A (en) | 2016-10-11 | 2024-02-23 | 艾吉纳斯公司 | anti-LAG-3 antibodies and methods of use thereof |
CA3041717A1 (en) | 2016-11-09 | 2018-05-17 | North Carolina State University | Treatment of allergic diseases with chimeric protein |
JP7217229B2 (en) | 2016-11-15 | 2023-02-02 | ハー・ルンドベック・アクチエゼルスカベット | Agents, uses and methods for the treatment of synucleinopathies |
JOP20170192A1 (en) | 2016-12-01 | 2019-01-30 | Takeda Pharmaceuticals Co | Cyclic dinucleotide |
EP3551225A1 (en) | 2016-12-07 | 2019-10-16 | Agenus Inc. | Antibodies and methods of use thereof |
SG10201912560YA (en) | 2016-12-07 | 2020-02-27 | Agenus Inc | Anti-ctla-4 antibodies and methods of use thereof |
MA47019A (en) | 2016-12-16 | 2021-04-21 | H Lundbeck As | AGENTS, USES AND METHODS |
US10364286B2 (en) | 2016-12-22 | 2019-07-30 | H. Lundbeck A/S | Monoclonal anti-alpha-synuclein antibodies for preventing tau aggregation |
MA47205A (en) | 2017-01-04 | 2019-11-13 | H Lundbeck As | SPECIFIC ANTIBODIES OF HYPERPHOSPHORYLATED TAU PROTEIN TO TREAT EYE DISEASES |
US11046775B2 (en) | 2017-02-14 | 2021-06-29 | Kite Pharma, Inc. | CD70 binding molecules and methods of use thereof |
TW201837175A (en) | 2017-03-13 | 2018-10-16 | 美商凱特製藥公司 | Chimeric antigen receptors for melanoma and uses thereof |
CN110753702B (en) | 2017-03-15 | 2022-09-20 | 清华大学 | anti-TRKB antibodies |
EA201992278A1 (en) | 2017-03-27 | 2020-03-03 | Селджин Корпорейшн | METHODS AND COMPOSITIONS FOR REDUCING IMMUNOGENOUS |
KR20190135017A (en) | 2017-03-30 | 2019-12-05 | 더 유니버서티 어브 퀸슬랜드 | Chimeric Molecules and Their Uses |
MX2019012223A (en) | 2017-04-13 | 2019-12-09 | Agenus Inc | Anti-cd137 antibodies and methods of use thereof. |
CA3059938A1 (en) | 2017-04-14 | 2018-10-18 | Kodiak Sciences Inc. | Complement factor d antagonist antibodies and conjugates thereof |
KR20190141659A (en) | 2017-04-21 | 2019-12-24 | 스태튼 바이오테크놀로지 비.브이. | Anti-APOC3 Antibodies and Methods of Use thereof |
JOP20180042A1 (en) | 2017-04-24 | 2019-01-30 | Kite Pharma Inc | Humanized Antigen-Binding Domains and Methods of Use |
AU2018263857A1 (en) | 2017-05-01 | 2019-11-21 | Agenus Inc. | Anti-TIGIT antibodies and methods of use thereof |
CN110881274A (en) | 2017-05-02 | 2020-03-13 | 普罗塞纳生物科学有限公司 | Antibodies recognizing TAU |
JOP20190256A1 (en) | 2017-05-12 | 2019-10-28 | Icahn School Med Mount Sinai | Newcastle disease viruses and uses thereof |
US11655307B2 (en) | 2017-05-30 | 2023-05-23 | The Board Of Regents Of The University Of Oklahoma | Anti-doublecortin-like kinase 1 antibodies and methods of use |
JP7235733B2 (en) | 2017-06-05 | 2023-03-08 | ヤンセン バイオテツク,インコーポレーテツド | Antibodies that specifically bind to PD-1 and methods of use |
EP3652540A4 (en) | 2017-07-12 | 2021-04-07 | The Johns Hopkins University | A proteoliposome-based znt8 self-antigen for type 1 diabetes diagnosis |
US10894833B2 (en) | 2017-07-20 | 2021-01-19 | H. Lundbeck A/S | Agents, uses and methods for treatment |
JP2020528936A (en) | 2017-07-27 | 2020-10-01 | ノモキャン ファーマシューティカルズ エルエルシー | Antibodies to M (H) DM2 / 4 and their use in the diagnosis and treatment of cancer |
CA3070774A1 (en) | 2017-08-25 | 2019-02-28 | Five Prime Therapeutics, Inc. | B7-h4 antibodies and methods of use thereof |
AU2018334279A1 (en) | 2017-09-15 | 2020-04-02 | Kite Pharma, Inc. | Methods and systems for performing a patient-specific immunotherapy procedure with chain-of-custody and chain-of-identity biological sample tracking |
DE112018005145T5 (en) | 2017-09-15 | 2020-07-23 | The Regents Of The University Of California | INHIBITION OF AMINOACYLASE 3 (AA3) IN TREATMENT OF CANCER |
IL273252B2 (en) | 2017-09-20 | 2024-03-01 | Mersana Therapeutics Inc | Compositions and methods for predicting response to napi2b-targeted therapy |
WO2019060713A1 (en) | 2017-09-22 | 2019-03-28 | Kite Pharma, Inc. | Antigen binding molecules and methods of use thereof |
AU2017434556A1 (en) | 2017-09-28 | 2020-04-09 | F. Hoffmann-La Roche Ag | Dosing regimes for treatment of synucleinopathies |
EP3700932A1 (en) | 2017-10-27 | 2020-09-02 | Kite Pharma, Inc. | T cell receptor antigen binding molecules and methods of use thereof |
BR112020008514A2 (en) | 2017-10-31 | 2020-10-20 | Staten Biotechnology B.V. | anti-apoc3 antibodies and methods of using them |
EP3710471A1 (en) | 2017-11-16 | 2020-09-23 | Kite Pharma, Inc. | Modified chimeric antigen receptors and methods of use |
CN111448213A (en) | 2017-12-01 | 2020-07-24 | 西雅图基因公司 | CD47 antibodies and their use for treating cancer |
BR112020010694A2 (en) | 2017-12-01 | 2020-11-10 | Abbvie Inc. | glucocorticoid receptor agonist and immunoconjugates of the same |
BR112020010937A2 (en) | 2017-12-01 | 2020-11-17 | Seattle Genetics, Inc. | humanized anti-liv1 antibodies for the treatment of breast cancer |
US20190225689A1 (en) | 2018-01-22 | 2019-07-25 | Janssen Biotech, Inc. | Methods of treating cancers with antagonistic anti-pd-1 antibodies |
EP4253959A3 (en) | 2018-02-14 | 2023-11-22 | Kite Pharma, Inc. | Anti-idiotypic antibodies directed to the antigen-binding portion of an bcma-binding molecule |
CA3091161A1 (en) | 2018-02-21 | 2019-08-29 | Five Prime Therapeutics, Inc. | B7-h4 antibody dosing regimens |
EP3755720A1 (en) | 2018-02-21 | 2020-12-30 | Five Prime Therapeutics, Inc. | B7-h4 antibody formulations |
US11686013B2 (en) | 2018-02-23 | 2023-06-27 | Meso Scale Technologies, Llc. | Methods of screening antigen-binding molecules by normalizing for the concentration of antigen-binding molecule |
AU2019228600A1 (en) | 2018-03-02 | 2020-09-24 | Five Prime Therapeutics, Inc. | B7-H4 antibodies and methods of use thereof |
EP3765523A1 (en) | 2018-03-12 | 2021-01-20 | Memorial Sloan Kettering Cancer Center | Bispecific binding agents and uses thereof |
US12060437B2 (en) | 2018-03-23 | 2024-08-13 | North Carolina State University | Methods and compositions for antibody to high affinity receptor for IgE |
EA202092849A1 (en) | 2018-05-24 | 2021-03-16 | Янссен Байотек, Инк. | Monospecific and multispecific antibodies to TMEFF2 AND THEIR APPLICATION |
CN112513085B (en) | 2018-05-24 | 2024-06-18 | 詹森生物科技公司 | PSMA binding agents and uses thereof |
JP7530299B2 (en) | 2018-05-24 | 2024-08-07 | ヤンセン バイオテツク,インコーポレーテツド | Anti-CD3 antibodies and uses thereof |
US12006357B2 (en) | 2018-06-26 | 2024-06-11 | Mor Research Applications Ltd. | Transthyretin antibodies and uses thereof |
PE20211091A1 (en) | 2018-07-02 | 2021-06-14 | Amgen Inc | ANTI-STEAP1 ANTIGEN BINDING PROTEIN |
CN112672788A (en) | 2018-07-24 | 2021-04-16 | 免疫医疗有限责任公司 | Antibodies against Staphylococcus aureus agglutinin A (CLFA) |
TW202035452A (en) | 2018-08-17 | 2020-10-01 | 美商梅爾莎納醫療公司 | Napi2b-targeted polymer antibody-drug conjugates and methods of use thereof |
WO2020070678A2 (en) | 2018-10-03 | 2020-04-09 | Staten Biotechnology B.V. | Antibodies specific for human and cynomolgus apoc3 and methods of use thereof |
AU2019357983A1 (en) | 2018-10-09 | 2021-05-27 | Medimmune, Llc | Combinations of anti-staphylococcus aureus antibodies |
JP7459075B2 (en) | 2018-10-09 | 2024-04-01 | メディミューン,エルエルシー | Antibodies directed against Staphylococcus aureus leukotoxin |
TWI835885B (en) | 2018-10-15 | 2024-03-21 | 美商戊瑞治療有限公司 | Combination therapy for cancer |
EP3817773B1 (en) | 2018-11-26 | 2024-07-24 | Forty Seven, Inc. | Humanized antibodies against c-kit |
KR20210094609A (en) | 2018-11-28 | 2021-07-29 | 포티 세븐, 인코포레이티드 | Genetically Modified HSPCs Resistant to Ablation Regimes |
BR112021012172A2 (en) | 2018-12-12 | 2021-08-31 | Kite Pharma, Inc. | CHIMERIC AND T-CELL ANTIGEN RECEPTORS AND METHODS OF USE |
CN113508136A (en) | 2018-12-21 | 2021-10-15 | 艾维迪提生物科学公司 | Anti-transferrin receptor antibodies and uses thereof |
RU2711871C1 (en) * | 2018-12-25 | 2020-01-23 | Федеральное государственное автономное образовательное учреждение высшего образования "Российский национальный исследовательский медицинский университет имени Н.И. Пирогова" Министерства здравоохранения Российской Федерации (ФГАОУ ВО РНИМУ им. Н.И. Пирогова Минздрава России) | Monoclonal antibodies which specifically bind to the beta-chain region of the trbv-9 family of the human t-cell receptor, and methods for use thereof |
MX2021008392A (en) | 2019-01-10 | 2021-10-26 | Janssen Biotech Inc | Prostate neoantigens and their uses. |
AU2020216295A1 (en) | 2019-01-28 | 2021-09-09 | Maple Biotech Llc | PSMP antagonists for use in treatment of fibrotic disease of the lung, kidney or liver |
EP3917968A1 (en) | 2019-01-30 | 2021-12-08 | Nomocan Pharmaceuticals LLC | Antibodies to m(h)dm2/4 and their use in diagnosing and treating cancer |
MX2021009138A (en) | 2019-02-05 | 2021-09-10 | Seagen Inc | Anti-cd228 antibodies and antibody-drug conjugates. |
EP3930744A1 (en) | 2019-03-01 | 2022-01-05 | Allogene Therapeutics, Inc. | Dll3 targeting chimeric antigen receptors and binding agents |
CA3131531A1 (en) | 2019-03-03 | 2020-09-10 | Prothena Biosciences Limited | Antibodies recognizing tau |
WO2020185986A1 (en) | 2019-03-13 | 2020-09-17 | Medimmune, Llc | Decreasing staphylococcus aureus infections in colonized patients |
WO2020210650A1 (en) | 2019-04-12 | 2020-10-15 | Medimmune, Llc | Neutralization of tgf-beta or alpha-v-beta-8 integrin for s. aureus infections |
EP3956022A1 (en) | 2019-04-19 | 2022-02-23 | Janssen Biotech, Inc. | Methods of treating prostate cancer with an anti- psma/cd3 antibody |
CA3132476A1 (en) | 2019-04-19 | 2020-10-22 | Thomas Charles PERTEL | Antibodies against 4g7-derived chimeric antigen receptors |
MX2021013380A (en) | 2019-04-30 | 2021-11-25 | Gigagen Inc | Recombinant polyclonal proteins and methods of use thereof. |
EA202193121A1 (en) | 2019-05-15 | 2022-02-21 | Неоткс Терапьютикс Лтд. | CANCER TREATMENT |
EP3972653A1 (en) | 2019-05-22 | 2022-03-30 | Massachusetts Institute of Technology | Circular rna compositions and methods |
MA56120A (en) | 2019-06-07 | 2022-04-13 | Amgen Inc | B-SPECIFIC LINK CONSTRUCTIONS |
CA3138501A1 (en) | 2019-06-13 | 2020-12-17 | Thomas Charles PERTEL | Anti-talen antibodies and uses thereof |
CA3143271A1 (en) | 2019-06-21 | 2020-12-24 | Kite Pharma, Inc. | Tgf-.beta. receptors and methods of use |
TW202116810A (en) | 2019-07-22 | 2021-05-01 | 美商西雅圖遺傳學股份有限公司 | Humanized anti-liv1 antibodies for the treatment of cancer |
US20210040210A1 (en) | 2019-07-26 | 2021-02-11 | Janssen Biotech, Inc. | Proteins Comprising Kallikrein Related Peptidase 2 Antigen Binding Domains And Their Uses |
MX2022002315A (en) | 2019-08-30 | 2022-03-25 | Agenus Inc | Anti-cd96 antibodies and methods of use thereof. |
JP2022549504A (en) | 2019-09-26 | 2022-11-25 | エスティーキューブ アンド カンパニー | Antibodies specific for glycosylated CTLA-4 and methods of use thereof |
WO2021067776A2 (en) | 2019-10-04 | 2021-04-08 | Seagen Inc. | Anti-pd-l1 antibodies and antibody-drug conjugates |
EP4041768A1 (en) | 2019-10-09 | 2022-08-17 | StCube & Co. | Antibodies specific to glycosylated lag3 and methods of use thereof |
AU2020364071A1 (en) | 2019-10-10 | 2022-05-26 | Kodiak Sciences Inc. | Methods of treating an eye disorder |
WO2021081330A1 (en) | 2019-10-23 | 2021-04-29 | Kite Pharma, Inc. | Anti-idiotypic antigen binding molecules and methods of use thereof |
PE20221182A1 (en) | 2019-11-18 | 2022-08-05 | Janssen Biotech Inc | VACCINES BASED ON CALR AND JAK2 MUTANTS AND THEIR USES |
TW202138388A (en) | 2019-12-30 | 2021-10-16 | 美商西根公司 | Methods of treating cancer with nonfucosylated anti-cd70 antibodies |
EP4087652A1 (en) | 2020-01-08 | 2022-11-16 | Regeneron Pharmaceuticals, Inc. | Treatment of fibrodysplasia ossificans progressiva |
KR20220129044A (en) * | 2020-01-16 | 2022-09-22 | 카이로스 테라퓨틱스 인코포레이티드 | Humanized Antibodies Specific to Myeloma and Ovarian Cancer Cells |
AU2021214795A1 (en) | 2020-01-31 | 2022-08-18 | The Cleveland Clinic Foundation | Anti-Müllerian Hormone Receptor 2 antibodies and methods of use |
TW202140012A (en) | 2020-02-12 | 2021-11-01 | 比利時商健生藥品公司 | Fgfr tyrosine kinase inhibitors and anti-pd1 agents for the treatment of urothelial carcinoma |
TW202144389A (en) | 2020-02-14 | 2021-12-01 | 美商健生生物科技公司 | Neoantigens expressed in multiple myeloma and their uses |
TW202144388A (en) | 2020-02-14 | 2021-12-01 | 美商健生生物科技公司 | Neoantigens expressed in ovarian cancer and their uses |
EP4107173A1 (en) | 2020-02-17 | 2022-12-28 | Board of Regents, The University of Texas System | Methods for expansion of tumor infiltrating lymphocytes and use thereof |
BR112022016368A2 (en) | 2020-02-18 | 2023-01-10 | Alector Llc | PILRA ANTIBODIES AND THEIR METHODS OF USE |
IL296242A (en) | 2020-03-10 | 2022-11-01 | Massachusetts Inst Technology | Methods for generating engineered memory-like nk cells and compositions thereof |
KR20220167276A (en) | 2020-03-10 | 2022-12-20 | 매사추세츠 인스티튜트 오브 테크놀로지 | Compositions and methods for immunotherapy of NPM1c-positive cancers |
EP4233893A3 (en) | 2020-03-13 | 2023-09-27 | Janssen Biotech, Inc. | Materials and methods for binding siglec-3/cd33 |
US11555190B2 (en) | 2020-03-19 | 2023-01-17 | Avidity Biosciences, Inc. | Compositions and methods of treating Facioscapulohumeral muscular dystrophy |
WO2021186398A1 (en) | 2020-03-19 | 2021-09-23 | Medimmune Limited | Anti-klebsiella pneumoniae antibodies and uses thereof |
EP4121453A2 (en) | 2020-03-20 | 2023-01-25 | Orna Therapeutics, Inc. | Circular rna compositions and methods |
WO2021195362A1 (en) | 2020-03-26 | 2021-09-30 | Seagen Inc. | Methods of treating multiple myeloma |
JP2023527638A (en) | 2020-03-27 | 2023-06-30 | アビディティー バイオサイエンシーズ,インク. | Compositions and methods for treating facioscapulohumeral muscular dystrophy |
KR20230028217A (en) | 2020-04-17 | 2023-02-28 | 뉴욕 유니버시티 | Therapeutic MuSK Antibodies |
TW202208423A (en) | 2020-05-17 | 2022-03-01 | 英商阿斯特捷利康英國股份有限公司 | Sars-cov-2 antibodies and methods of selecting and using the same |
CA3179423A1 (en) | 2020-05-19 | 2021-11-25 | Robert Alexander WESSELHOEFT | Circular rna compositions and methods |
MX2022014938A (en) | 2020-05-27 | 2023-03-06 | Janssen Biotech Inc | Proteins comprising cd3 antigen binding domains and uses thereof. |
CN115698068A (en) | 2020-06-02 | 2023-02-03 | 艾库斯生物科学有限公司 | anti-TIGIT antibody |
EP4161969A1 (en) | 2020-06-04 | 2023-04-12 | Amgen Inc. | Bispecific binding constructs |
CA3177152A1 (en) | 2020-06-12 | 2021-12-16 | David Scott Johnson | Recombinant polyclonal proteins targeting covid-19 and methods of use thereof |
CA3183994A1 (en) | 2020-06-24 | 2021-12-30 | Philip James Dolan Iii | Antibodies recognizing sortilin |
JP2023534520A (en) | 2020-07-20 | 2023-08-09 | アストラゼネカ・ユーケイ・リミテッド | SARS-COV-2 proteins, anti-SARS-COV-2 antibodies, and methods of use thereof |
CN116209681A (en) | 2020-07-29 | 2023-06-02 | 詹森生物科技公司 | Proteins comprising HLA-G antigen binding domains and uses thereof |
WO2022031834A1 (en) | 2020-08-05 | 2022-02-10 | Gigagen, Inc. | Recombinant polyclonal proteins targeting zika and methods of use thereof |
EP4192511A1 (en) | 2020-08-07 | 2023-06-14 | Fortis Therapeutics, Inc. | Immunoconjugates targeting cd46 and methods of use thereof |
CN116234577A (en) | 2020-08-10 | 2023-06-06 | 阿斯利康(英国)有限公司 | SARS-COV-2 antibodies for the treatment and prevention of COVID-19 |
IL299911A (en) | 2020-08-14 | 2023-03-01 | Kite Pharma Inc | Improving immune cell function |
AU2021329378A1 (en) | 2020-08-19 | 2023-03-23 | Xencor, Inc. | Anti-CD28 compositions |
CN116348593A (en) | 2020-08-21 | 2023-06-27 | 上海吉倍生物技术有限公司 | Antibodies that specifically bind glycosylated CEACAM5 |
WO2022046760A2 (en) | 2020-08-25 | 2022-03-03 | Kite Pharma, Inc. | T cells with improved functionality |
AU2021332460A1 (en) | 2020-08-27 | 2023-04-06 | Enosi Therapeutics Corporation | Methods and compositions to treat autoimmune diseases and cancer |
KR20230079154A (en) | 2020-09-28 | 2023-06-05 | 씨젠 인크. | Humanized Anti-LIV1 Antibodies for Cancer Treatment |
UY39467A (en) | 2020-10-13 | 2022-04-29 | Janssen Biotech Inc | BIOENGINEERED T-CELL-MEDIATED IMMUNITY, MATERIALS, AND OTHER METHODS TO MODULATE DIFFERENTIATION GROUP IV AND/OR VIII |
CN116783217A (en) | 2020-12-03 | 2023-09-19 | 安进公司 | Immunoglobulin constructs with multiple binding domains |
WO2022140388A1 (en) | 2020-12-21 | 2022-06-30 | Allogene Therapeutics, Inc. | Protease-activating cd45-gate car |
AU2021410635A1 (en) | 2020-12-24 | 2023-06-29 | Kite Pharma, Inc. | Prostate cancer chimeric antigen receptors |
EP4284838A2 (en) | 2021-01-28 | 2023-12-06 | Janssen Biotech, Inc. | Psma binding proteins and uses thereof |
IL303847A (en) | 2021-01-28 | 2023-08-01 | Allogene Therapeutics Inc | Methods for transducing immune cells |
WO2022165233A1 (en) | 2021-01-29 | 2022-08-04 | Allogene Therapeutics, Inc. | KNOCKDOWN OR KNOCKOUT OF ONE OR MORE OF TAP2, NLRC5, β2m, TRAC, RFX5, RFXAP AND RFXANK TO MITIGATE T CELL RECOGNITION OF ALLOGENEIC CELL PRODUCTS |
WO2022178090A2 (en) | 2021-02-19 | 2022-08-25 | Theripion, Inc. | Dnase fusion polypeptides and related compositions and methods |
CA3208496A1 (en) | 2021-03-04 | 2022-09-09 | Michael Thomas Bethune | Fasl expression and fasr gene knockout to protect therapeutic cells from allogeneic rejection and activation-induced cell death |
KR20230155521A (en) | 2021-03-11 | 2023-11-10 | 카이트 파마 인코포레이티드 | Improved immune cell function |
KR20230160314A (en) | 2021-03-24 | 2023-11-23 | 얀센 바이오테크 인코포레이티드 | Antibodies targeting CD22 and CD79B |
CA3216056A1 (en) | 2021-04-16 | 2022-10-20 | Kite Pharma, Inc. | Taci/bcma dual binding molecules |
KR20240013173A (en) | 2021-05-24 | 2024-01-30 | 카이트 파마 인코포레이티드 | NKG2D-based chimeric antigen receptor |
EP4347657A1 (en) | 2021-05-25 | 2024-04-10 | Seagen Inc. | Methods of quantifying anti-cd40 antibodies |
CN113393899A (en) * | 2021-05-26 | 2021-09-14 | 江苏普瑞康生物医药科技有限公司 | Method and device for antibody humanization based on dynamic programming |
CN117730100A (en) | 2021-06-08 | 2024-03-19 | 凯德药业股份有限公司 | GPC3 binding molecules |
KR20240019791A (en) | 2021-06-10 | 2024-02-14 | 오나 테라퓨틱스, 인코포레이티드 | Circular RNA compositions and methods |
CA3218481A1 (en) | 2021-06-14 | 2022-12-22 | argenx BV | Anti-il-9 antibodies and methods of use thereof |
IL308468A (en) | 2021-06-15 | 2024-01-01 | Allogene Therapeutics Inc | Selective targeting of host cd70+ alloreactive cells to prolong allogeneic car t cell persistence |
WO2022263632A1 (en) | 2021-06-18 | 2022-12-22 | Alligator Bioscience Ab | Novel combination therapies and uses thereof |
EP4359430A2 (en) | 2021-06-23 | 2024-05-01 | Lycia Therapeutics, Inc. | Bifunctional compounds containing igf-2 polypeptides |
WO2023278377A1 (en) | 2021-06-29 | 2023-01-05 | Seagen Inc. | Methods of treating cancer with a combination of a nonfucosylated anti-cd70 antibody and a cd47 antagonist |
WO2023279099A1 (en) | 2021-07-01 | 2023-01-05 | Denali Therapeutics Inc. | Oligonucleotide conjugates targeted to the transferrin receptor |
AU2022310346A1 (en) | 2021-07-14 | 2024-01-25 | Lycia Therapeutics, Inc. | M6pr cell surface receptor binding compounds and conjugates |
CN117957020A (en) | 2021-07-14 | 2024-04-30 | 利西亚治疗公司 | ASGPR cell surface receptor binding compounds and conjugates |
US20230060292A1 (en) | 2021-07-26 | 2023-03-02 | Kite Pharma, Inc. | Split chimeric antigen receptors and methods of use |
CA3229526A1 (en) | 2021-08-16 | 2023-02-23 | Hemogenyx Pharmaceuticals Llc | Anti-flt3 antibodies, cars, car t cells and methods of use |
CA3229520A1 (en) | 2021-08-17 | 2023-02-23 | Hemogenyx Pharmaceuticals Llc | Bispecific anti-flt3/cd3 antibodies and methods of use |
KR20240099138A (en) | 2021-08-23 | 2024-06-28 | 이뮤니타스 테라퓨틱스, 인크. | Anti-CD161 antibodies and uses thereof |
PE20240727A1 (en) | 2021-08-27 | 2024-04-15 | Janssen Biotech Inc | ANTI-PSMA ANTIBODIES AND USES OF THESE |
JPWO2023032955A1 (en) | 2021-08-31 | 2023-03-09 | ||
AU2022345098A1 (en) | 2021-09-16 | 2024-04-04 | Avidity Biosciences, Inc. | Compositions and methods of treating facioscapulohumeral muscular dystrophy |
TW202327650A (en) | 2021-09-23 | 2023-07-16 | 美商思進公司 | Methods of treating multiple myeloma |
EP4405392A1 (en) | 2021-09-24 | 2024-07-31 | Janssen Biotech, Inc. | Proteins comprising cd20 binding domains, and uses thereof |
AU2022358522A1 (en) | 2021-09-30 | 2024-03-28 | Seagen Inc. | B7-h4 antibody-drug conjugates for the treatment of cancer |
TW202322851A (en) | 2021-09-30 | 2023-06-16 | 美商歐納醫療公司 | Lipid nanoparticle compositions for delivering circular polynucleotides |
EP4419559A1 (en) | 2021-10-18 | 2024-08-28 | Kite Pharma, Inc. | Signaling domains for chimeric antigen receptors |
WO2023066336A1 (en) * | 2021-10-21 | 2023-04-27 | 江苏先声药业有限公司 | Anti-muc17 nanobody and use thereof |
WO2023072159A1 (en) | 2021-10-27 | 2023-05-04 | Virtuoso Binco, Inc. | Multispecific antibodies for treating cd47-associated diseases |
TW202342095A (en) | 2021-11-05 | 2023-11-01 | 英商阿斯特捷利康英國股份有限公司 | Composition for treatment and prevention of covid-19 |
AU2022383068A1 (en) | 2021-11-08 | 2024-05-02 | Orna Therapeutics, Inc. | Lipid nanoparticle compositions for delivering circular polynucleotides |
WO2023131219A1 (en) | 2022-01-06 | 2023-07-13 | Virtuoso Binco, Inc. | Conjugates, compositions and methods of use |
WO2023152581A1 (en) | 2022-02-09 | 2023-08-17 | Janssen Biotech, Inc. | Method of treating cancer with psmaxcd3 antibody |
TW202342510A (en) | 2022-02-18 | 2023-11-01 | 英商Rq生物科技有限公司 | Antibodies |
US20230346934A1 (en) | 2022-03-29 | 2023-11-02 | Allogene Therapeutics, Inc. | Chimeric switch receptors for the conversion of immunesuppressive signals to costimulatory signals |
WO2023209177A1 (en) | 2022-04-29 | 2023-11-02 | Astrazeneca Uk Limited | Sars-cov-2 antibodies and methods of using the same |
WO2023218099A1 (en) | 2022-05-13 | 2023-11-16 | argenx BV | In utero treatment of a fetus having genetic disease/neuromuscular disease |
WO2023247050A1 (en) | 2022-06-23 | 2023-12-28 | Alligator Bioscience Ab | Combination therapies |
US20240052049A1 (en) | 2022-06-24 | 2024-02-15 | Orna Therapeutics, Inc. | Circular rna encoding chimeric antigen receptors targeting bcma |
GB202210957D0 (en) | 2022-07-27 | 2022-09-07 | Alligator Bioscience Ab | Novel dosages |
GB202210965D0 (en) | 2022-07-27 | 2022-09-07 | Alligator Bioscience Ab | Novel dosages |
TW202405020A (en) | 2022-07-29 | 2024-02-01 | 美商阿列克特有限責任公司 | Transferrin receptor antigen-binding domains and uses therefor |
WO2024026471A1 (en) | 2022-07-29 | 2024-02-01 | Alector Llc | Cd98hc antigen-binding domains and uses therefor |
WO2024026445A1 (en) | 2022-07-29 | 2024-02-01 | Allogene Therapeutics Inc. | Engineered cells with reduced gene expression to mitigate immune cell recognition |
US20240091261A1 (en) | 2022-08-26 | 2024-03-21 | Kite Pharma, Inc. | Immune cell function |
WO2024051806A1 (en) * | 2022-09-09 | 2024-03-14 | 南京金斯瑞生物科技有限公司 | Method for designing humanized antibody sequence |
US20240101710A1 (en) | 2022-09-19 | 2024-03-28 | Allogene Therapeutics, Inc. | B-cell maturation antigen (bcma) anti-idiotypic antibodies |
GB202215115D0 (en) | 2022-10-13 | 2022-11-30 | Univ Nottingham | VEGF antibodies |
WO2024102762A1 (en) | 2022-11-08 | 2024-05-16 | Orna Therapeutics, Inc. | Lipids and lipid nanoparticle compositions for delivering polynucleotides |
WO2024102730A1 (en) | 2022-11-08 | 2024-05-16 | Orna Therapeutics, Inc. | Lipids and nanoparticle compositions for delivering polynucleotides |
US20240226313A1 (en) | 2022-11-17 | 2024-07-11 | Sanofi | Ceacam5 antibody-drug conjugates and methods of use thereof |
US20240216430A1 (en) | 2022-11-28 | 2024-07-04 | Allogene Therapeutics, Inc. | Claudin 18.2 targeting chimeric antigen receptors and binding agents and uses thereof |
WO2024129756A1 (en) | 2022-12-13 | 2024-06-20 | Seagen Inc. | Site-specific engineered cysteine antibody drug conjugates |
US20240228639A1 (en) | 2022-12-14 | 2024-07-11 | Allogene Therapeutics, Inc. | Cd70 anti-idiotype antibodies |
WO2024129982A2 (en) | 2022-12-15 | 2024-06-20 | Orna Therapeutics, Inc. | Circular rna compositions and methods |
WO2024155746A1 (en) | 2023-01-18 | 2024-07-25 | Lycia Therapeutics, Inc. | Cycling lysosomal targeting antibody conjugates |
WO2024155748A1 (en) | 2023-01-18 | 2024-07-25 | Lycia Therapeutics, Inc. | M6pr binding compounds and conjugates |
WO2024155747A2 (en) | 2023-01-18 | 2024-07-25 | Lycia Therapeutics, Inc. | Asgpr binding compounds and conjugates |
EP4406973A1 (en) | 2023-01-27 | 2024-07-31 | Fundació Privada Institut de Recerca de la SIDA-Caixa | Antibodies and uses thereof for the treatment of infections caused by enveloped viruses |
Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6479284B1 (en) * | 1998-03-13 | 2002-11-12 | Dana-Farber Cancer Institute, Inc. | Humanized antibody and uses thereof |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5225539A (en) | 1986-03-27 | 1993-07-06 | Medical Research Council | Recombinant altered antibodies and methods of making altered antibodies |
US5530101A (en) | 1988-12-28 | 1996-06-25 | Protein Design Labs, Inc. | Humanized immunoglobulins |
US5859205A (en) | 1989-12-21 | 1999-01-12 | Celltech Limited | Humanised antibodies |
JP4124480B2 (en) | 1991-06-14 | 2008-07-23 | ジェネンテック・インコーポレーテッド | Immunoglobulin variants |
US5869619A (en) | 1991-12-13 | 1999-02-09 | Xoma Corporation | Modified antibody variable domains |
FR2724393A1 (en) * | 1994-09-12 | 1996-03-15 | Inst Nat Sante Rech Med | OBTAINING A HUMANIZED RECOMBINANT MONOCLONAL ANTIBODY FROM A MURIN MONOCLONAL ANTIBODY, ITS PRODUCTION IN INSECT CELLS, AND USES THEREOF |
US6881557B2 (en) * | 2001-07-12 | 2005-04-19 | Arrowsmith Technologies Llp | Super humanized antibodies |
-
2002
- 2002-07-12 US US10/194,975 patent/US6881557B2/en not_active Expired - Lifetime
- 2002-07-12 CA CA2491864A patent/CA2491864C/en not_active Expired - Lifetime
- 2002-07-12 EP EP02752269A patent/EP1539233B1/en not_active Revoked
- 2002-07-12 AU AU2002368077A patent/AU2002368077B2/en not_active Expired
- 2002-07-12 IL IL16624402A patent/IL166244A0/en unknown
- 2002-07-12 EP EP10185475A patent/EP2298809A3/en not_active Withdrawn
- 2002-07-12 JP JP2004521391A patent/JP2005538706A/en not_active Withdrawn
- 2002-07-12 WO PCT/US2002/022011 patent/WO2004006955A1/en active Search and Examination
- 2002-07-12 CN CN02829598.6A patent/CN1671416B/en not_active Expired - Lifetime
- 2002-07-12 MX MXPA05000511A patent/MXPA05000511A/en active IP Right Grant
-
2005
- 2005-02-08 US US11/054,669 patent/US7732578B2/en not_active Expired - Lifetime
-
2006
- 2006-05-10 US US11/432,734 patent/US7709226B2/en not_active Expired - Lifetime
-
2010
- 2010-03-29 US US12/749,257 patent/US20110137014A1/en not_active Abandoned
Patent Citations (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6479284B1 (en) * | 1998-03-13 | 2002-11-12 | Dana-Farber Cancer Institute, Inc. | Humanized antibody and uses thereof |
Non-Patent Citations (5)
Title |
---|
MHASHILKAR A.M. ET AL.: "Inhibition of human immunodeficiency virus type 1 replication in vitro in acutely and persistently infected human CD4+ mononuclear cells expressing murine and humanized anti-human immunodeficiency virus type 1 Tat single-chain variable fragment intrabodies", HUMAN GENE THERAPY, vol. 10, 10 June 1999 (1999-06-10), pages 1453 - 1467, XP002928231 * |
MOREA V. ET AL.: "Antibody modeling: Implications for engineering and design", METHODS, vol. 20, no. 3, 2000, pages 267 - 279, XP004466884 * |
ROSOK M.J. ET AL.: "A combinatorial library strategy for the rapid humanization of anticarcinoma BR96 Fab", THE JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 271, no. 37, 13 September 1996 (1996-09-13), pages 22611 - 22618, XP002920742 * |
See also references of EP1539233A4 * |
WU H. ET AL.: "Humanization of a murine monoclonal antibody by simultaneous optimization of framework and CDR residues", JOURNAL OF MOLECULAR BIOLOGY, vol. 294, 1999, pages 151 - 162, XP002166821 * |
Cited By (101)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7575893B2 (en) | 2003-01-23 | 2009-08-18 | Genentech, Inc. | Methods for producing humanized antibodies and improving yield of antibodies or antigen binding fragments in cell culture |
US7981843B2 (en) | 2004-01-20 | 2011-07-19 | Kalobios Pharmaceuticals, Inc. | Antibody specificity transfer using minimal essential binding determinants |
EP2404935A1 (en) | 2004-03-30 | 2012-01-11 | Glaxo Group Limited | Immunoglobulin binding HOSM |
WO2005112564A3 (en) * | 2004-04-15 | 2007-01-18 | Us Gov Health & Human Serv | Germline and sequence variants of humanized antibodies and methods of making and using them |
WO2005112564A2 (en) * | 2004-04-15 | 2005-12-01 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Germline and sequence variants of humanized antibodies and methods of making and using them |
US10919983B2 (en) | 2004-11-16 | 2021-02-16 | Humanigen, Inc. | Immunoglobulin variable region cassette exchange |
EP3540062A1 (en) * | 2004-11-16 | 2019-09-18 | Humanigen, Inc. | Immunoglobulin variable region cassette exchange |
WO2006055778A2 (en) | 2004-11-16 | 2006-05-26 | Kalobios, Inc. | Immunoglobulin variable region cassette exchange |
EP2343380A1 (en) * | 2004-11-16 | 2011-07-13 | Kalobios Inc. | Immunoglobulin variable region cassette exchange |
EP1824987A4 (en) * | 2004-11-16 | 2008-03-19 | Kalobios Inc | Immunoglobulin variable region cassette exchange |
EP1824987A2 (en) * | 2004-11-16 | 2007-08-29 | Kalobios Inc. | Immunoglobulin variable region cassette exchange |
US7855276B2 (en) | 2004-12-30 | 2010-12-21 | The United States Of America As Represented By The Department Of Health And Human Services | Framework residue substituted humanized COL-1 antibodies and their use |
US8828717B2 (en) | 2004-12-30 | 2014-09-09 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Framework residue substituted humanized COL-1 antibodies and their use |
JP2008531060A (en) * | 2005-03-04 | 2008-08-14 | バイオジェン・アイデック・エムエイ・インコーポレイテッド | A method for humanizing immunoglobulin variable regions via rational modification of complementarity determining residues |
US7678371B2 (en) | 2005-03-04 | 2010-03-16 | Biogen Idec Ma Inc. | Methods of humanizing immunoglobulin variable regions through rational modification of complementarity determining residues |
US8349324B2 (en) | 2005-03-04 | 2013-01-08 | Biogen Idec Ma Inc. | Methods of humanizing immunoglobulin variable regions through rational modification of complementarity determining residues |
WO2006096653A2 (en) * | 2005-03-04 | 2006-09-14 | Biogen Idec Ma Inc. | Methods of humanizing immunoglobulin variable regions through rational modification of complementarity determining residues |
WO2006096653A3 (en) * | 2005-03-04 | 2007-07-12 | Biogen Idec Inc | Methods of humanizing immunoglobulin variable regions through rational modification of complementarity determining residues |
AU2006220709B2 (en) * | 2005-03-04 | 2012-09-06 | Biogen Ma Inc. | Methods of humanizing immunoglobulin variable regions through rational modification of complementarity determining residues |
JP2009502171A (en) * | 2005-07-25 | 2009-01-29 | トゥルビオン・ファーマシューティカルズ・インコーポレーテッド | Reduction of B cells using CD37-specific and CD20-specific binding molecules |
US10307481B2 (en) | 2005-07-25 | 2019-06-04 | Aptevo Research And Development Llc | CD37 immunotherapeutics and uses thereof |
JP2012165760A (en) * | 2005-07-25 | 2012-09-06 | Emergent Product Development Seattle Llc | B-cell reduction using cd37-specific and cd20-specific binding molecules |
US10143748B2 (en) | 2005-07-25 | 2018-12-04 | Aptevo Research And Development Llc | B-cell reduction using CD37-specific and CD20-specific binding molecules |
JP2014196350A (en) * | 2005-07-25 | 2014-10-16 | エマージェント・プロダクト・ディベロップメント・シアトル・エルエルシー | B-cell reduction using cd37-specific and cd20-specific binding molecules |
EP2228391A2 (en) | 2005-12-16 | 2010-09-15 | Glaxo Group Limited | Immunoglobulins directed against Nogo |
WO2007068750A2 (en) | 2005-12-16 | 2007-06-21 | Glaxo Group Limited | Immunoglobulins directed against nogo |
EP2423229A1 (en) | 2006-03-27 | 2012-02-29 | Medimmune Limited | Binding member for GM-CSF receptor |
EP2423230A1 (en) | 2006-03-27 | 2012-02-29 | Medimmune Limited | Binding member for GM-CSF receptor |
WO2007137984A2 (en) | 2006-05-25 | 2007-12-06 | Glaxo Group Limited | Modified humanised anti-interleukin-18 antibodies |
WO2008017126A1 (en) | 2006-08-11 | 2008-02-14 | Csl Limited | Treatment of pulmonary disease conditions |
EP2526959A1 (en) | 2006-08-11 | 2012-11-28 | CSL Limited | Treatment of pulmonary disease conditions |
EP2530090A2 (en) | 2006-10-19 | 2012-12-05 | CSL Limited | Anti-IL-13R alpha 1 antibodies and their uses thereof |
EP2628751A2 (en) | 2006-11-30 | 2013-08-21 | AstraZeneca AB | Binding members for interleukin-6 and use thereof |
EP2620452A1 (en) | 2007-02-15 | 2013-07-31 | Medimmune Limited | Binding members for IGE molecules |
US10494432B2 (en) | 2007-07-16 | 2019-12-03 | Genentech, Inc. | Anti-CD79B antibodies and immunoconjugates and methods of use |
US11866496B2 (en) | 2007-07-16 | 2024-01-09 | Genentech, Inc. | Humanized anti-CD79B antibodies and immunoconjugates and methods of use |
US10981987B2 (en) | 2007-07-16 | 2021-04-20 | Genentech, Inc. | Humanized anti-CD79b antibodies and immunoconjugates and methods of use |
JP2010533495A (en) * | 2007-07-16 | 2010-10-28 | ジェネンテック, インコーポレイテッド | Humanized CD79b antibodies and immunoconjugates and their use |
USRE48558E1 (en) | 2007-07-16 | 2021-05-18 | Genentech, Inc. | Anti-CD79B antibodies and immunoconjugates and methods of use |
US9845355B2 (en) | 2007-07-16 | 2017-12-19 | Genentech, Inc. | Humanized anti-CD79b antibodies and immunoconjugates and methods of use |
JP2014207919A (en) * | 2007-07-16 | 2014-11-06 | ジェネンテック, インコーポレイテッド | HUMANIZED ANTI-CD79b ANTIBODIES AND IMMUNOCONJUGATES, AND METHODS OF USING THE SAME |
EP2050765A1 (en) * | 2007-10-19 | 2009-04-22 | Centocor, Inc. | Methods for use in human-adapting monoclonal antibodies |
US8748356B2 (en) | 2007-10-19 | 2014-06-10 | Janssen Biotech, Inc. | Methods for use in human-adapting monoclonal antibodies |
US10544218B2 (en) | 2008-01-31 | 2020-01-28 | Genentech, Inc. | Anti-CD79B antibodies and immunoconjugates and methods of use |
KR20160116056A (en) | 2008-08-14 | 2016-10-06 | 테바 파마슈티컬즈 오스트레일리아 피티와이 엘티디 | Anti-il-12/il-23 antibodies |
US8741604B2 (en) | 2008-11-07 | 2014-06-03 | Medimmune Limited | Nucleic acid molecule encoding a specific IL-1R1 antibody |
US8298533B2 (en) | 2008-11-07 | 2012-10-30 | Medimmune Limited | Antibodies to IL-1R1 |
US9200074B2 (en) | 2008-11-07 | 2015-12-01 | Medimmune Limited | Antibodies to IL-1 R1 and methods of making them |
WO2010070094A1 (en) | 2008-12-19 | 2010-06-24 | Glaxo Group Limited | Myostatin binding proteins |
WO2011076883A1 (en) | 2009-12-23 | 2011-06-30 | 4-Antibody Ag | Binding members for human cytomegalovirus |
WO2011094259A2 (en) | 2010-01-28 | 2011-08-04 | Glaxo Group Limited | Cd127 binding proteins |
US11026407B2 (en) | 2010-02-08 | 2021-06-08 | Regeneran Pharmaceuticals, Inc. | Mice expressing a limited immunoglobulin light chain repertoire |
US10412940B2 (en) | 2010-02-08 | 2019-09-17 | Regeneron Pharmaceuticals, Inc. | Mice expressing a limited immunoglobulin light chain repertoire |
US10143186B2 (en) | 2010-02-08 | 2018-12-04 | Regeneron Pharmaceuticals, Inc. | Common light chain mouse |
US10167344B2 (en) | 2010-02-08 | 2019-01-01 | Regeneron Pharmaceuticals, Inc. | Mice expressing a limited immunoglobulin light chain repertoire |
US9969814B2 (en) | 2010-02-08 | 2018-05-15 | Regeneron Pharmaceuticals, Inc. | Methods for making fully human bispecific antibodies using a common light chain |
US10986820B2 (en) | 2010-02-08 | 2021-04-27 | Regeneron Pharmaceuticals, Inc. | Common light chain mouse |
US9796788B2 (en) | 2010-02-08 | 2017-10-24 | Regeneron Pharmaceuticals, Inc. | Mice expressing a limited immunoglobulin light chain repertoire |
EP3025729A1 (en) | 2010-03-03 | 2016-06-01 | Glaxo Group Limited | Antigen binding proteins specific for serum amyloid p component |
WO2011107480A1 (en) | 2010-03-03 | 2011-09-09 | Glaxo Group Limited | Antigen binding proteins specific for serum amyloid p component |
WO2011151432A1 (en) | 2010-06-03 | 2011-12-08 | Glaxo Group Limited | Humanised antigen binding proteins to myostatin6 |
US9605063B2 (en) | 2010-11-23 | 2017-03-28 | Glaxo Group Limited | Antigen binding proteins to Oncostatin M (OSM) |
EP3211009A1 (en) * | 2010-11-23 | 2017-08-30 | Glaxo Group Limited | Antigen binding proteins to oncostatin m (osm) |
WO2012069433A3 (en) * | 2010-11-23 | 2012-08-09 | Glaxo Group Limited | Antigen binding proteins to oncostatin m (osm) |
EA027256B1 (en) * | 2010-11-23 | 2017-07-31 | Глаксо Груп Лимитед | ANTIGEN BINDING PROTEINS WHICH BIND HUMAN ONCOSTATIN M (hOSM) |
WO2012085015A1 (en) | 2010-12-20 | 2012-06-28 | Medimmune Limited | Anti-il-18 antibodies and their uses |
US10130081B2 (en) | 2011-08-05 | 2018-11-20 | Regeneron Pharmaceuticals, Inc. | Humanized universal light chain mice |
US11357217B2 (en) | 2011-08-05 | 2022-06-14 | Regeneron Pharmaceuticals, Inc. | Humanized universal light chain mice |
US11186638B2 (en) | 2011-09-12 | 2021-11-30 | Genzyme Corporation | Anti-αβTCR antibody |
WO2013053767A1 (en) | 2011-10-10 | 2013-04-18 | Medimmune Limited | Treatment for rheumatoid arthritis |
US10196440B2 (en) | 2011-12-20 | 2019-02-05 | Janssen Biotech, Inc. | Anti-PHG-tau antibodies and their uses |
US9371376B2 (en) | 2011-12-20 | 2016-06-21 | Janssen Biotech, Inc. | Anti-PHF-tau antibodies and their uses |
US9745371B2 (en) | 2011-12-20 | 2017-08-29 | Janssen Biotech, Inc. | Anti-PHF-tau antibodies and their uses |
US10000559B2 (en) | 2011-12-20 | 2018-06-19 | Janssen Biotech, Inc. | Anti-PHF-tau antibodies and their uses |
WO2013096380A2 (en) | 2011-12-20 | 2013-06-27 | Janssen Biotech, Inc. | Anti-phf-tau antibodies and their uses |
EP3578567A1 (en) | 2011-12-20 | 2019-12-11 | Janssen Biotech, Inc. | Anti-phf-tau antibodies and their uses |
WO2014006105A1 (en) | 2012-07-05 | 2014-01-09 | Glaxo Group Limited | Optimum dose regime of an anti-nogo-a antibody in the treatment of amyotrophic lateral sclerosis |
EP3721942A1 (en) | 2012-10-15 | 2020-10-14 | Medimmune Limited | Antibodies to amyloid beta |
WO2014072306A1 (en) | 2012-11-08 | 2014-05-15 | F. Hoffmann-La Roche Ag | Her3 antigen binding proteins binding to the beta-hairpin of her3 |
US11807690B2 (en) | 2013-03-11 | 2023-11-07 | Genzyme Corporation | Hyperglycosylated binding polypeptides |
US11697690B2 (en) | 2014-03-19 | 2023-07-11 | Genzyme Corporation | Site-specific glycoengineering of targeting moieties |
US10881085B2 (en) | 2014-03-21 | 2021-01-05 | Regeneron Pharmaceuticals, Inc. | Non-human animals that make single domain binding proteins |
WO2015179435A1 (en) | 2014-05-19 | 2015-11-26 | Bayer Healthcare Llc | Optimized humanized monoclonal antibodies against activated protein c and uses thereof |
WO2016001140A1 (en) | 2014-06-30 | 2016-01-07 | Affiris Ag | Vaccines and monoclonal antibodies targeting truncated variants of osteopontin and uses thereof |
US10406197B2 (en) | 2014-07-10 | 2019-09-10 | Affiris Ag | Substances and methods for the use in prevention and/or treatment in Huntington's disease |
US12016842B2 (en) | 2014-09-23 | 2024-06-25 | Genentech, Inc. | Methods of using anti-CD79b immunoconjugates |
US11000510B2 (en) | 2014-09-23 | 2021-05-11 | Genentech, Inc. | Methods of using anti-CD79b immunoconjugates |
WO2016059602A2 (en) | 2014-10-16 | 2016-04-21 | Glaxo Group Limited | Methods of treating cancer and related compositions |
US10793642B2 (en) | 2014-12-11 | 2020-10-06 | Inbiomotion S.L. | Binding members for human c-MAF |
WO2016092524A1 (en) | 2014-12-11 | 2016-06-16 | Inbiomotion S.L. | Binding members for human c-maf |
US11111314B2 (en) | 2015-03-19 | 2021-09-07 | Regeneron Pharmaceuticals, Inc. | Non-human animals that select for light chain variable regions that bind antigen |
WO2017158064A1 (en) | 2016-03-15 | 2017-09-21 | Astrazeneca Ab | Combination of a bace inhibitor and an antibody or antigen-binding fragment for the treatment of a disorder associated with the accumulation of amyloid beta |
EP3434690A4 (en) * | 2016-03-23 | 2020-04-01 | Seoul National University R&DB Foundation | Antibody that binds to envelope glycoprotein of severe fever with thrombocytopenia syndrome virus, and use for same |
US10947299B2 (en) | 2016-03-23 | 2021-03-16 | Seoul National University R&Db Foundation | Antibody that binds to envelope glycoprotein of severe fever with thrombocytopenia syndrome virus and use for same |
WO2018170351A1 (en) | 2017-03-16 | 2018-09-20 | Janssen Biotech, Inc. | Anti-phf-tau antibodies and uses thereof |
US11365244B2 (en) | 2017-03-16 | 2022-06-21 | Janssen Biotech, Inc. | Anti-PHF-tau antibodies and uses thereof |
US10766953B2 (en) | 2017-03-16 | 2020-09-08 | Janssen Biotech, Inc. | Anti-PHF-tau antibodies and uses thereof |
US11680110B2 (en) | 2017-07-31 | 2023-06-20 | Hoffmann-La Roche Inc. | Three-dimensional structure-based humanization method |
WO2019025299A1 (en) | 2017-07-31 | 2019-02-07 | F. Hoffmann-La Roche Ag | Three-dimensional structure-based humanization method |
US10633435B2 (en) | 2018-03-05 | 2020-04-28 | Janssen Pharmaceutica Nv | Anti-PHF-tau antibodies and uses thereof |
WO2022201122A1 (en) | 2021-03-26 | 2022-09-29 | Janssen Biotech, Inc. | Humanized antibodies against paired helical filament tau and uses thereof |
Also Published As
Publication number | Publication date |
---|---|
MXPA05000511A (en) | 2005-09-30 |
AU2002368077B2 (en) | 2010-03-04 |
US6881557B2 (en) | 2005-04-19 |
CA2491864A1 (en) | 2004-01-22 |
US20110137014A1 (en) | 2011-06-09 |
EP2298809A2 (en) | 2011-03-23 |
IL166244A0 (en) | 2006-01-15 |
US7732578B2 (en) | 2010-06-08 |
CA2491864C (en) | 2012-09-11 |
CN1671416B (en) | 2013-01-02 |
CN1671416A (en) | 2005-09-21 |
EP1539233B1 (en) | 2011-04-27 |
EP1539233A1 (en) | 2005-06-15 |
EP2298809A3 (en) | 2012-02-15 |
US20050261480A1 (en) | 2005-11-24 |
US7709226B2 (en) | 2010-05-04 |
US20030039649A1 (en) | 2003-02-27 |
US20070003547A1 (en) | 2007-01-04 |
AU2002368077A2 (en) | 2004-02-02 |
EP1539233A4 (en) | 2006-04-05 |
AU2002368077A1 (en) | 2004-02-02 |
JP2005538706A (en) | 2005-12-22 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
AU2002368077B2 (en) | Super humanized antibodies | |
US20050288491A1 (en) | Super-humanized antibodies against respiratory syncytial virus | |
EP1542725B1 (en) | Method of humanizing immune system molecules | |
EP0699755B1 (en) | Method for obtaining modified immunoglobulins with reduced immunogenicity of murine antibody variable domains, compositions containing them | |
EP2250199B1 (en) | Engineered anti-tslpr antibodies | |
CA2261026C (en) | Genetically engineered immunoglobulins with specificity for glycated albumin | |
JPH07504808A (en) | Humanized chimeric T cell antibody grafted with CDRs | |
JP2004073210A (en) | Modified antibody and product and process relating thereto | |
KR20140062127A (en) | Caninised antibodies and method for the production of same | |
US20040260068A1 (en) | Humanized chicken antibodies | |
JP2022545925A (en) | Anti-TFPI monoclonal antibody | |
Kaur | Overview of monoclonal antibodies | |
ES2370225T3 (en) | SUPERHUMANIZED ANTIBODIES. | |
JP2011115175A (en) | Super humanized antibody | |
MX2008005405A (en) | Horse: human chimeric antibodies. | |
WO2005014653A2 (en) | Humanized chicken antibodies | |
JP2012152223A (en) | Super humanized antibody |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
AK | Designated states |
Kind code of ref document: A1 Designated state(s): AE AG AL AM AT AU AZ BA BB BG BR BY BZ CA CH CN CO CR CU CZ DE DK DM DZ EC EE ES FI GB GD GE GH GM HR HU ID IL IN IS JP KE KG KP KR KZ LC LK LR LS LT LU LV MA MD MG MK MN MW MX MZ NO NZ OM PH PL PT RO RU SD SE SG SI SK SL TJ TM TN TR TT TZ UA UG UZ VN YU ZA ZM ZW |
|
AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): GH GM KE LS MW MZ SD SL SZ TZ UG ZM ZW AM AZ BY KG KZ MD RU TJ TM AT BE BG CH CY CZ DE DK EE ES FI FR GB GR IE IT LU MC NL PT SE SK TR BF BJ CF CG CI CM GA GN GQ GW ML MR NE SN TD TG |
|
121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
WWE | Wipo information: entry into national phase |
Ref document number: 2491864 Country of ref document: CA |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2002368077 Country of ref document: AU Ref document number: PA/a/2005/000511 Country of ref document: MX Ref document number: 166244 Country of ref document: IL |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2004521391 Country of ref document: JP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 44/KOLNP/2005 Country of ref document: IN |
|
WWE | Wipo information: entry into national phase |
Ref document number: 2002752269 Country of ref document: EP |
|
WWE | Wipo information: entry into national phase |
Ref document number: 20028295986 Country of ref document: CN |
|
WWP | Wipo information: published in national office |
Ref document number: 2002752269 Country of ref document: EP |
|
DPE2 | Request for preliminary examination filed before expiration of 19th month from priority date (pct application filed from 20040101) |