114 results about "Framework region" patented technology

An anti-Nectin-4 single-domain antibody and the use thereof. Provided are a single-domain antibody specifically targeting Nectin-4, and amino acid sequences of a framework region FR and a complementarity-determining region CDR of a VHH chain thereof. The anti-Nectin-4 single-domain antibody can bind to a Nectin-4 antigen. An antibody-drug conjugate and a multi-specific antibody targeting the Nectin-4 target prepared by means of using the single-domain antibody have an excellent activity and high therapeutic efficacy.

The invention discloses a T-2 toxin monoclonal antibody and application thereof, and belongs to the technical field of biology. The monoclonal antibody contains a heavy chain variable region and a light chain variable region, the heavy chain variable region and the light chain variable region are both composed of complementary determining regions and frame regions, and the complementary determining regions are both composed of CDR1, CDR2 and CDR3. The monoclonal antibody can be used for preparing a T-2 toxin detection product. The T-2 toxin colloidal gold test strip provided by the invention has the characteristics of high sensitivity, good specificity and strong stability.

The invention provides an anti-TNF (Tumor Necrosis Factor) alpha nano antibody and application thereof, and relates to a nano antibody, polypeptide containing the nano antibody, application of the nano antibody and the like, a variable region in an amino acid sequence of the nano antibody comprises three complementarity determining regions CDR and a framework region FR, the complementarity determining regions CDR comprise a complementarity determining region CDR1, a complementarity determining region CDR2 and a complementarity determining region CDR3, the main sites participating in antigen recognition and binding are RXXXXXE on CDR1 and ATYSDSPWNXXSFYXLSGVGA on CDR3, and the nano antibody and the polypeptide thereof have very high affinity and activity, can specifically recognize and bind TNF alpha, and can be used for adsorption, removal, detection and the like of TNF alpha.

The embodiment of the invention discloses an antibody generation method and device, computer equipment and a storage medium, and belongs to the technical field of computers. The method comprises the following steps: acquiring antigen information and frame region information, wherein the antigen information indicates amino acid in an antigen; performing feature extraction on the antigen information and the frame region information to obtain a first feature and a second feature; the first feature and the second feature are decoded, first antibody information is obtained, an antibody indicated by the first antibody information is used for being combined with the antigen, and the antibody comprises a frame area indicated by the frame area information. According to the invention, the stability and reliability of the antibody are ensured, the antibody information can be quickly generated aiming at the specific antigen information, the antibody generation efficiency is improved, the framework area can be specified for the antibody to be generated, the personalized configuration of the generated antibody is ensured, and the flexibility of antibody generation is ensured.

Provided are a nanobody targeting YAP and a use thereof. The nanobody targeting YAP comprises three complementarity determining regions and four framework regions. The three complementary determining regions are CDR1, CDR2, and CDR3, respectively, and the four framework regions are FR1, FR2, FR3, and FR4, respectively. The amino acid sequence of CDR1 is as shown in SEQ ID NO. 1, the amino acid sequence of CDR2 is as shown in SEQ ID NO. 2, and the amino acid sequence of CDR3 is as shown in SEQ ID NO. 3 or SEQ ID NO. 4; and the amino acid sequence of FR1 is as shown in SEQ ID NO. 5, the amino acid sequence of FR2 is as shown in SEQ ID NO. 6 or SEQ ID NO. 7, the amino acid sequence of FR3 is as shown in SEQ ID NO. 8 or SEQ ID NO. 9, and the amino acid sequence of FR4 is as shown in SEQ ID NO. 10 or SEQ ID NO. 11. The nanobody targeting YAP has a relatively high binding force to YAP. By means of the targeting effect of the antibody on YAP, the development of a drug related to a nanobody against YAP is facilitated, and targeted treatment of a disease associated with YAP is implemented.

Disclosed is a method for improving affinity of an antibody for an antigen, the method comprising: in the antibody, changing at least 3 amino acid residues of framework region 3 (FR3) as defined by Kabat method to arginine residues or lysine residues, thereby improving affinity of an antibody for an antigen as compared with that of an antibody before said at least 3 amino acid residues are changed to arginine residues or lysine residues, wherein said at least 3 amino acid residues comprise at least 3 selected from the group consisting of amino acid residues at positions 68, 70, 72, 74, 75, 77, 79, 81, 82A, 82B, 83, 84, 85 and 87 of a heavy chain as defined by the Kabat method.

The disclosure provides a polypeptide comprising an antibody heavy chain variable domain (VH) variant comprising a plurality of antigen-binding regions and a framework comprising framework region 1, framework region 2 and framework region 3 (FWR3), wherein the VH variant has an amino acid sequence in which at least eight of the following criteria i) to x) are fulfilled: i) the residue in Kabat position 19 is R, S, K or T; ii) the residue in Kabat position 23 is T, V, A or S; iii) the residue in Kabat position 24 is I, V or S; iv) the residue in Kabat position 40 is selected from R, I, T or K; v) the residue in Kabat position 43 is R, K, Q, E or G; vi) the residue in Kabat position 44 is E, Q, A, D or G; vii) the residue in Kabat position 45 is R, I or L; viii) the residue in Kabat position 76 is N or Q; ix) the residue in Kabat position 79 is Y, A, W or F; and x) the residue in Kabat position 89 is V, I, L or A. The VH variants have improved alkaline stability and are useful as a scaffold for an affinity binder for in vitro applications, such as detection, analysis or separation of an analyte based on affinity interactions.

Aspects of the disclosure relate to PD-1 binding proteins comprising immunoglobulin domains which bind specifically to PD-1 and comprise at least three or six specific complementarity determining regions (CDRs) and which comprise a specific feature in a variable domain framework region(s), e.g., heavy variable domain framework 1, heavy domain framework 4, and / or light chain variable domain framework 3 region(s). In some embodiments, the PD-1 protein comprises the substitution(s) L 108G and / or THOR of the heavy chain reference sequence and / or 158R relative to the light chain reference sequence(s). The PD-1 binding proteins are useful, e.g., as immunologic adjuvants, for detecting and quantifying PD-1, monitoring patient responses to therapies, diagnosing PD-1 related conditions, and treating or preventing disorders involving PD-1 expressing cells, such as, e.g., cancers and autoimmune diseases. Also provided herein are antigen binding proteins comprising amino acid substitutions in the heavy chain framework 4 region for improved stability and solubility.

This invention relates to monoclonal antibodies for detecting A35R protein and their applications. This invention screened six antibodies, including antibody 4E7, antibody 11G12, antibody 6F10, antibody 6C11, antibody 18C3, and antibody 23A7. Specifically, this invention discloses the amino acid sequences of the heavy chain variable region and the light chain variable region of the above antibodies, as well as the amino acid sequences of their complementarity-determining regions and framework regions. Antibodies 4E7 and 11G12 can bind not only to the A35R-MPXV protein but also to its homologs A35R-CPXV, A35R-VTT8, and A35R-Variola. Antibodies 6F10, 6C11, 23A7, and 18C3 can specifically recognize the A35R-MPXV protein. The monoclonal antibodies described above all exhibit high binding capacity to the A35R protein, making them suitable for the sensitive and specific detection and prevention of monkeypox virus A35R protein. They can also be used clinically for the diagnosis and treatment of monkeypox virus infection-related diseases.

The present invention belongs to the technical fields of molecular biology and immunology, and provides a camelid-derived nanobody that specifically binds to the trypsin analogue TrypLE and its application. It has a heavy chain variable region VHH, and the VHH contains the following CDRs: CDR1 with the amino acid sequence shown in SEQ ID NO:1, CDR2 with the amino acid sequence shown in SEQ ID NO:2, CDR3 with the amino acid sequence shown in SEQ ID NO:3. The VHH includes 4 framework regions of FR1-4, and FR1, FR2, FR3 and FR4 are arranged alternately with CDR1, CDR2 and CDR3 in sequence. It is a nanobody with high neutralizing activity, has a strong binding ability to TrypLE protein, can effectively recognize TrypLE. This nanobody has a small molecular weight, low immunogenicity, better solubility and stability, and a longer CDR region, providing potential application value for the clinical detection of TrypLE residue content.

The present invention relates to the biological field and discloses an anti-CALR mutant protein antibody, which comprises a framework region and a complementary determining region; the complementary determining region comprises CDR-VH1, CDR-VH2 and CDR-VH3, CDR-VL1, CDR-VL2 and CDR-VL3; the complementary determining region CDR-VH1 sequence is SEQ ID NO.1; the complementary determining region CDR-VH2 sequence is SEQ ID NO.2; the complementary determining region CDR-VH3 sequence is SEQ ID NO.3; the complementary determining region CDR-VL1 sequence is SEQ ID NO.4; the complementary determining region CDR-VL2 sequence is SEQ ID NO.5; the complementary determining region CDR-VL3 sequence is SEQ ID NO.6.

The application discloses a NbP2 single-domain antibody, a TAT-NbP2 fusion single-domain antibody and application thereof, and belongs to the technical field of biological medicines. The NbP2 single-domain antibody is composed of a framework region FR and three complementarity determining regions CDR1, CDR2 and CDR3, the amino acid sequence of the CDR1 is shown as SEQ ID NO. 1, the amino acid sequence of the CDR2 is shown as SEQ ID NO. 2, and the amino acid sequence of the CDR3 is shown as SEQ ID NO. 3. The TAT-NbP2 fusion single-domain antibody is a fusion protein of the NbP2 single-domain antibody and a TAT peptide segment of HIV-1 virus. The NbP2 single-domain antibody and the TAT-NbP2 fusion single-domain antibody provided by the application have dual activities of anti-virus and anti-inflammation, are safe, and provide a new idea for treating SARS-CoV-2 infection and developing anti-SARS-CoV-2 drugs.

Provided herein are components for antigen-binding constructs, including antibodies and fragments thereof, such as minibodies and cys-diabodies, that bind to target molecules, e.g., DLL3. In some embodiments, these components are novel complementarity-determining region (CDR) sequences and / or sequences related to and / or portions of CDR sequences. In some embodiments, these components are novel framework region (FR) sequences and / or sequences related to and / or portions of FR sequences. These CDR and FR sequences may provide various benefits. Also provided herein are antigen-binding constructs (minibodies, cys-diabodies, etc.) that include one or more of the CDR or FR sequences or subsequences provided herein.

This invention provides low-viscosity antigen-binding proteins and methods for producing them. [Solution] The present invention relates to a method for reducing the viscosity of an antigen-binding protein by modifying the sequence in the framework region and / or Fc domain, which has been shown to be associated with high viscosity. The present invention provides antigen-binding proteins, particularly antibodies, that have been mutated to reduce viscosity. Preferred antigen-binding proteins according to the present invention include antibodies, as shown in Figure 1B, having one or more, preferably all, of the following: VH1|1-18 germline subfamily substitution; VH3|3-33 germline subfamily substitution; VK3|L16 germline subfamily substitution; VK3|L6 germline subfamily substitution; or Fc substitution.

The present invention relates to humanized nanobodies targeting cadherin 17 and their applications, and to the technical fields of immunology and molecular biology. The complementary determining region of the humanized nanobody includes a CDR1 with an amino acid sequence as shown in SEQ ID NO: 2, a CDR2 with an amino acid sequence as shown in SEQ ID NO: 4, and a CDR3 with an amino acid sequence as shown in SEQ ID NO: 6; the framework region of the humanized nanobody includes a FR1 with an amino acid sequence as shown in any one of SEQ ID NO: 1 and SEQ ID NO: 8, an FR2 with an amino acid sequence as shown in any one of SEQ ID NO: 3, SEQ ID NO: 9, and SEQ ID NO: 11, an FR3 with an amino acid sequence as shown in any one of SEQ ID NO: 5 and SEQ ID NO: 10, and an FR4 with an amino acid sequence as shown in SEQ ID NO: 7. The humanized nanobody of the present invention reduces the immunogenicity of the nanobody, improves the target binding activity and killing activity, and can be used to develop immune detection reagents, CAR-T / NK cell drugs, and antibody drugs.

The application discloses a spiramycin monoclonal antibody and application thereof, and belongs to the technical field of biology. The monoclonal antibody contains a heavy chain variable region and a light chain variable region, the heavy chain variable region and the light chain variable region are both composed of a complementarity determining region and a framework region, and the complementarity determining region is composed of CDR1, CDR2 and CDR3. The monoclonal antibody can be used for preparing a spiramycin detection preparation. The spiramycin colloidal gold detection test strip provided by the application has the characteristics of high sensitivity, good specificity and strong stability.

Aspects of the disclosure relate to PD-1 binding proteins comprising immunoglobulin domains which bind specifically to PD-1 and comprise at least three or six specific complementarity determining regions (CDRs) and which comprise a specific feature in a variable domain framework region(s), e.g., heavy variable domain framework 1, heavy domain framework 4, and / or light chain variable domain framework 3 region(s). In some embodiments, the PD-1 protein comprises the substitution(s) L108G and / or T110R of the heavy chain reference sequence and / or I58R relative to the light chain reference sequence(s). The PD-1 binding proteins are useful, e.g., as immunologic adjuvants, for detecting and quantifying PD-1, monitoring patient responses to therapies, diagnosing PD-1 related conditions, and treating or preventing disorders involving PD-1 expressing cells, such as, e.g., cancers and autoimmune diseases. Also provided herein are antigen binding proteins comprising amino acid substitutions in the heavy chain framework 4 region for improved stability and solubility.

The present application relates to a kind of anti-CD276 nanobody, the anti-CD276 nanobody includes complementary determining region CDR and framework region FR;Wherein, the complementary determining region CDR includes complementary determining region CDR1-CDR3;The framework region FR includes framework region FR1-FR5.The anti-human CD276 nanobody provided by the present application has the immunoreaction characteristic with CD276 antigen, and specificity is good, and affinity is high, can be applied to the preparation of CD276 detection reagent or antitumor drug etc., the anti-human CD276 nanobody provided by the present application can be used as the antigen recognition domain of CAR Then the construction of CAR-T cell, it has significant killing effect to the multiple tumor cell lines of expression CD276 antigen;The anti-human CD276 nanobody provided by the present application can be used to detect the expression of CD276 in tumor tissue.

The invention belongs to the technical field of biological medicines, and particularly relates to an anti-CD22 nano antibody as well as a preparation method and application thereof. The anti-CD22 nano antibody comprises a framework region and a complementarity determining region, wherein the complementarity determining region comprises CDR1 (SEQ ID NO: 1), CDR2 (SEQ ID NO: 2) and CDR3 (SEQ ID NO: 3). The preparation method comprises the following steps: immunizing alpaca by using Human CD22 / His protein, extracting RNA (Ribonucleic Acid) from PBMC (Peripheral Blood Mononuclear Cell) and reversely transcribing into cDNA (Complementary Deoxyribose Nucleic Acid), constructing a phage display library, then performing CD22 antigen protein elutriation to obtain positive clone, and after sequencing analysis, expressing the antibody by using a mammalian cell expression system. The optimized phage display technology is adopted, the screening period is short, and the obtained nano antibody is small in molecular weight, stable in structure and high in affinity to CD22. The antibody can be efficiently expressed through mammalian cells, and natural modification activity is reserved.

The invention discloses an NbE7 single-domain antibody, an NbE7-TAT fusion single-domain antibody and application of the NbE7 single-domain antibody and the NbE7-TAT fusion single-domain antibody, the NbE7 single-domain antibody is used for being specifically combined with an EB virus nuclear antigen, the NbE7 single-domain antibody is composed of a framework region FR and a complementary determining region CDR, and the complementary determining region CDR comprises a CDR1 shown in SEQ ID NO.1, a CDR2 shown in SEQ ID NO.2 and a CDR3 shown in SEQ ID NO.3. The NbE7 single-domain antibody is used for being specifically combined with an EB virus nuclear antigen. The NbE7-TAT fusion single-domain antibody is a fusion protein of an NbE7 single-domain antibody and a TAT peptide fragment of an HIV-1 virus. The NbE7 single-domain antibody and the NbE7-TAT fusion single-domain antibody provided by the invention provide a new thought for the development of drugs for treating EBV latent infection and EB virus related tumors.

Provided is a target-molecule-specific functional protein control system comprising either: (a) a first nucleic acid molecule including a nucleic acid sequence which codes for a first fusion protein that includes a first domain of a functional protein and a first target binding domain including a light chain variable domain of an antibody which specifically recognizes a target molecule and (b) a second nucleic acid molecule including a nucleic acid sequence which codes for a second fusion protein that includes a second domain of the functional protein and a second target binding domain including a heavy chain variable domain of the antibody which specifically recognizes the target molecule; or (c) the first fusion protein and (d) the second fusion protein, wherein the framework region of one of the light chain variable domain and the heavy chain variable domain includes the sequence of the framework region of trastuzumab or a mutation sequence thereof, and the target molecule, the first target binding domain, and the second target binding domain form a ternary complex.

Human or chimeric heavy chain-only antibodies are provided, in the native amino acid residue at the first position of the fourth framework region (FR4) of said HCAb is substituted by a different amino acid residue that is capable of disrupting a surface-exposed hydrophobic patch comprising or associated with the native amino acid residue at that position.

The application provides a non-pH-dependent long-acting anti-serum albumin nanobody and an application thereof. Specifically, the application provides amino acid sequences of VHH chain framework regions FR and complementarity determining regions CDR of the non-pH-dependent long-acting anti-serum albumin nanobody. The application also provides nucleotide sequences encoding the nanobody. The anti-serum albumin nanobody provided by the application can bind to human, mouse, rat and cynomolgus serum albumin under different pH conditions, and can significantly prolong the half-life of a protein drug, thereby providing a research basis for long-acting protein drug development.

The present invention belongs to the technical field of biomedicine. Provided are a nanobody targeting IL-23A and the use thereof. The nanobody comprises a framework region and a complementarity determining region, wherein the framework region comprises FR-H1, FR-H2, FR-H3 and FR-H4 having amino acid sequences as shown in SEQ ID NOs. 4-7, respectively; and the complementary determining region comprises CDR-H1, CDR-H2 and CDR-H3 having amino acid sequences as shown in SEQ ID NOs. 1-3, respectively. The nanobody can be used in the preparation of an antibody drug targeting IL-23A, which is capable of treating related diseases by means of binding to IL-23A.

The present invention discloses a nanobody targeting IL-23A and an application thereof, and relates to the technical field of biological medicine. The nanobody VVH1 includes framework regions and complementary determining regions; the framework regions include VVH1FR-H1, VVH1FR-H2, VVH1FR-H3 and VVH1FR-H4, and the amino acid sequences of VVH1FR-H1, VVH1FR-H2, VVH1FR-H3 and VVH1FR-H4 are respectively shown as SEQ ID NOs. 4-7; and the complementary determining regions include VVH1CDR-H1, VVH1 CDR-H2 and VVH1 CDR-H3, and the amino acid sequences of VVH1 CDR-H1, VVH1 CDR-H2 and VVH1 CDR-H3 are respectively shown as SEQ ID NOs. 1-3. The nanobody has high binding activity with IL-23A, has the characteristics of small molecular weight, good stability, good tissue wettability, weak immunogenicity and the like compared with a traditional antibody, and can be applied to the preparation of an antibody drug targeting IL-23A so as to treat related diseases through combination with IL-23A.

The application belongs to the technical field of biological medicine, and particularly relates to an anti-FOLR1 nanobody and a preparation method and application thereof. The anti-FOLR1 nanobody comprises a framework region and a complementarity determining region, and the complementarity determining region amino acid comprises CDR1, CDR2 and CDR3. The application adopts automatic panning and a mammalian expression system, significantly improves the screening efficiency and antibody expression quality, greatly shortens the development cycle, and provides an efficient tool for FOLR1 targeted diagnosis and treatment. The obtained anti-FOLR1 nanobody exhibits excellent specific recognition and binding capacity.

The application provides an anti-CK8 nanobody, a polypeptide containing the nanobody and application thereof. A variable region in the amino acid sequence of the nanobody comprises three complementarity determining regions CDR and a framework region FR, the complementarity determining regions CDR comprising a complementarity determining region CDR1, a complementarity determining region CDR2 and a complementarity determining region CDR3, wherein the most important sites participating in antigen recognition and combination are RXXRXYX on the CDR1 and AASPAVSPPRDGRAFTY on the CDR3. The nanobody and the polypeptide thereof have high affinity and activity, can specifically recognize and combine CK8, and can be used for enrichment, removal and detection of CK8 and CK8 positive cells.

Provided herein are nanobodies, polypeptides comprising the same, and uses thereof. The nanobody's variable region includes 3 complementarity determining regions (CDRs) and framework regions (FRs), wherein the CDRs are as follows: CDR1: Ser-Gly-Xaa11-Xaa12-Phe-Xaa13-Xaa14-Asn-Xaa15 (Formula I); CDR2: Xaa21-Thr-Xaa22-Xaa23-Gly-Xaa24-Thr (Formula II); CDR3: His-Xaa31-Asp-Glu-Xaa32-Arg-Xaa33-Ser-Xaa34-Trp-Thr-Thr-Ser-Asn-Xaa35 (Formula III). The nanobodies and their polypeptides exhibit high affinity and activity, specifically recognizing and binding AAV. Affinity agents prepared therefrom have strong AAV adsorption capacity, suitable for AAV affinity chromatography to facilitate its industrial application. They are also applicable to AAV detection, enabling simultaneous detection of empty capsids and viral particles.

Disclosed are a nanobody targeting fibroblast activation protein-α, and the use thereof. An amino acid sequence of the nanobody comprises antigenic determinant complementary regions and framework regions with special structures. Firstly, alpacas are immunized with a recombinant FAPα antigen protein constructed to obtain a cell construct of alpaca PBMCs; secondly, an antibody targeting FAPα is screened by means of yeast display technology; and finally, an antibody having high sensitivity and specificity is obtained by means of functional detection and sequencing result analysis. The provided nanobody has the ability to specifically recognize and bind to FAPα, and has the characteristics of small molecular weight, low immunogenicity, better stability, a significant inhibitory effect on FAPα-expressing cells or tissues, etc., thus providing a potential therapeutic strategy for a disease involving FAPα expression. When the nanobody is used for developing or screening a diagnostic or therapeutic drug for FAPα-expressing cells or tissues, the obtained drug has excellent specificity and affinity, and has a significant inhibitory effect on FAPα-expressing cells or tissues.

The present invention provides a nanobody and its applications. The variable region in the amino acid sequence of the nanobody includes complementarity-determining regions CDR and framework regions FR. The complementarity-determining regions CDR include complementarity-determining region CDR1, complementarity-determining region CDR2, and complementarity-determining region CDR3. Among them, CDR3 belongs to the RWPDXY family, and the binding sites to the AAV capsid are W99, D101, and Y103. The nanobody of the present invention has high affinity and activity, can specifically recognize and bind multiple serotypes of AAV, the adsorbent prepared by this nanobody has extremely strong adsorption ability for AAV, can be applied to AAV affinity chromatography, and is conducive to the industrial application of AAV affinity chromatography columns. In addition, it can also be applied to the field of AAV detection, and can detect both empty capsids and virus particles at the same time.