# US 9,750,806 B2 · Vaccine preparation containing trifunctional antibodies with antigen immunogenicity enhancer properties > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 9,750,806 B2 - Document ID: US9750806B2 - Status: Granted - Kind: B2 - Application number: 14/118,212 - Filed: 2012-05-16 - Published: 2014-09-25 - Granted: 2017-09-05 - Earliest claimed: 2011-05-17 - Assignees: TRION Research Gmbh - Applicants: Horst Lindhofer - Inventors: Horst Lindhofer - Web page: https://patentgrep.com/patent/US9750806B2 ## CPC - A61K 39/3955: {against proteinaceous materials, e.g. enzymes, hormones, lymphokines} - A61K 39/0005: {Vertebrate antigens (from snakes A61K39/38)} - A61K 39/385: Haptens or antigens, bound to carriers - C07K 16/283: {against Fc-receptors, e.g. CD16, CD32, CD64 (CD23 C07K16/2851)} - C07K 16/30: from tumour cells - C07K 16/468: {Immunoglobulins having two or more different antigen binding sites, e.g. multifunctional antibodies} - A61K 2039/505: {comprising antibodies} - A61K 2300/00: Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00 - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C07K 2317/31: multispecific - C07K 2317/732: Antibody-dependent cellular cytotoxicity [ADCC] - A61K: PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES (devices or methods specially adapted for bringing pharmaceutical products into particular physical or administering forms A61J3/00; chemical aspects of, or use of materials for deodorisation of air, for disinfection or sterilisation, or for bandages, dressings, absorbent pads or surgical articles A61L; soap compositions C11D) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) ## Abstract The present invention refers to a pharmaceutical composition containing trifunctional bispecific and/or trispecific antibodies being capable of binding to a specific target antigen(s) for use in a method of immunizing mammals against diseases in which said target antigen(s) is (are) involved, and further to a pharmaceutical composition containing trifunctional bispecific and/or trispecific antibodies being capable of binding to (a) specific target antigen (s) which is (are) involved in a disease of a mammal, specifically a human. ## Claims ### Claim 1 A pharmaceutical composition comprising: 1) a trifunctional bispecific antibody and/or a trispecific antibody having the following properties: (a) binding to a T cell via CD3 and activating said T cell; (b) binding to a target antigen other than CD3; (c) binding to Fcγ-receptor type I, II and/or III positive cells via an Fc-portion, or by a third antigen specificity; and 2) a pharmaceutically acceptable carrier selected from the group consisting of homologous virus-like particles (VLP) and heterologous/chimeric VLP, wherein said target antigen and optionally one or more further antigens are associated with or conjugated to the VLP. ### Claim 2 (depends on 1) The pharmaceutical composition according to claim 1 wherein said target antigen is carrier-specific but not disease-associated and wherein one or more further antigens are disease-associated and conjugated to or associated with the VLP. ### Claim 3 (depends on 1) The pharmaceutical composition according to claim 1, wherein said target antigen is a disease-specific target antigen selected from the group consisting of antigens specific for tumors, viruses, bacteria, fungi, and protozoa, or an immunologically active epitope thereof. ### Claim 4 (depends on 1) The pharmaceutical composition according to claim 1, wherein said target antigen is a carrier protein or an immunologically active epitope thereof. ### Claim 5 (depends on 1) The pharmaceutical composition according to claim 1, wherein said composition is in the form of a vaccine formulation. ### Claim 6 (depends on 1) The pharmaceutical composition according to claim 1 wherein said one or more further antigens are conjugated to or associated with the VLP. ### Claim 7 (depends on 6) The pharmaceutical composition according to claim 6 wherein the target antigen is displayed by the VLP. ### Claim 8 (depends on 1) The pharmaceutical composition according to claim 1 wherein said target antigen is a non-disease associated antigen conjugated to or associated with one or more disease-associated antigens. ### Claim 9 (depends on 1) The pharmaceutical composition according to claim 1, wherein said carrier has a medium diameter of about 10-500 nm, and/or wherein said trifunctional bispecific and/or trispecific antibody is contained in an amount of about 1-10 μg, and/or wherein said target antigen is contained in an amount of about 0.1-500 μg. ### Claim 10 A kit comprising two containers, the first container containing a trifunctional bispecific and/or trispecific antibody having the following properties: (a) binding to a T cell via CD3 and activating said T cell; (b) binding to a target antigen other than CD3; (c) binding to Fcγ-receptor type I, II and/or III positive cells via an Fc-portion, or by a third antigen specificity; and a second container containing a carrier selected from the group consisting of homologous virus-like particles (VLP) and heterologous/chimeric VLP, wherein said target antigen and optionally one or more further antigens are conjugated to or associated with the VLP. ### Claim 11 (depends on 10) A kit according to claim 10 wherein said target antigen is carrier-specific but not disease-associated, and wherein one or more further antigens are disease-associated and conjugated to or associated with the VLP. ### Claim 12 (depends on 1) A method for immunizing a mammal subject, comprising administering to said subject a pharmaceutically effective amount of the pharmaceutical composition of claim 1 to evoke a cell-mediated or a humoral immune response or a combination thereof against said target antigen and said optionally one or more further antigens to immunize said mammal subject against said target antigen and said optionally one or more further antigens. ### Claim 13 (depends on 12) The method according to claim 12, wherein said target antigen is a disease-specific target antigen selected from the group consisting of antigens specific for tumors, viruses, bacteria, fungi, and protozoa, or an immunologically active epitope thereof. ### Claim 14 (depends on 12) The method according to claim 12, wherein said target antigen is a carrier protein or an immunologically active epitope thereof. ### Claim 15 (depends on 12) The method according to claim 12, wherein said one or more further antigens are conjugated to or associated with the VLP. ### Claim 16 (depends on 15) The method according to claim 15, wherein said target antigen is displayed by the VLP. ### Claim 17 (depends on 12) The method according to claim 12, wherein said trifunctional antibody is a rat/mouse bispecific antibody. ### Claim 18 (depends on 12) The method according to claim 12, wherein said trifunctional bispecific antibody is selected from at least one member of the following group of isotype combinations in its Fc-region: rat-IgG2b/mouse-IgG2a, rat-IgG2b/mouse-IgG2b, rat-IgG2b/human-IgG1, and human-IgG1/human-IgG1-[hinge]-human-IgG3*-[CH2-CH3], wherein * denotes Caucasian allotypes G3m (b+g) with no binding to protein A. ### Claim 19 (depends on 12) The method according to claim 12, wherein said trifunctional bispecific antibody is an anti-target antigen×anti-CD3 antibody having the isotype combination of rat-IgG2b/mouse-IgG2a. ### Claim 20 (depends on 12) The method according to claim 12, wherein said trifunctional bispecific or trispecific antibodies are administered in an amount of about 1-10 μg, optionally wherein said administration is repeated two or three times. ### Claim 21 (depends on 12) The method according to claim 12, wherein said target antigen is administered in an amount of about 0.1-500 μg. ### Claim 22 (depends on 12) The method according to claim 12, wherein said target antigen is a disease-associated antigen selected from the group consisting of tumor-associated antigens, fungal antigens, viral antigens, protozoan and bacterial antigens. ### Claim 23 (depends on 12) The method according to claim 12, wherein said target antigen is carrier-specific but not disease-associated, and wherein one or more further antigens are disease-associated and conjugated to or associated with the VLP.