# US 2019/0169280 A1 · Compositions for treating amyloidosis > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2019/0169280 A1 - Document ID: US20190169280A1 - Status: Published application - Kind: A1 - Application number: 16/314,143 - Filed: 2017-06-30 - Published: 2019-06-06 - Earliest claimed: 2016-06-30 - Assignees: Prothena Biosciences Limited - Applicants: Prothena Biosciences Limited - Inventors: GENE G. KINNEY; SPENCER D. GUTHRIE; MARTIN KOLLER - Web page: https://patentgrep.com/patent/US20190169280A1 ## CPC - C07K 16/18: against material from animals or humans - A61K 9/0019: {Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner (non-active ingredients are additionally classified in A61K47/00)} - A61P 25/02: for peripheral neuropathies - A61K 38/00: Medicinal preparations containing peptides (peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00) - A61K 2039/505: {comprising antibodies} - C07K 2317/24: containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered - C07K 2317/34: Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues - C07K 2317/565: Complementarity determining region [CDR] - C07K 2317/569: Single domain, e.g. dAb, sdAb, VHH, VNAR or nanobody® - 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) - 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) - A61P: SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS ## Abstract Antibody formulations and methods useful for treatment of peripheral neuropathy in patients with AL amyloidosis. ## Claims ### Claim 1 A method of treating a patient with peripheral neuropathy associated with AL amyloidosis, comprising administering an effective dosage of an antibody which competes for binding to human amyloid A peptide with antibody 2A4 (ATCC Accession Number 9662), thereby improving the neuropathy in the patient. ### Claim 2 (depends on 1) The method of claim 1, wherein progression of the peripheral neuropathy is reversed. ### Claim 3 (depends on 1) The method of claim 1, wherein the antibody or antigen-binding fragment thereof is a humanized version of 2A4. ### Claim 4 (depends on 1) The method of claim 1, wherein the antibody comprises a light chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 6, 7 and 8, and a heavy chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 9, 10 and 11. ### Claim 5 (depends on 4) The method of claim 4, wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 4. ### Claim 6 (depends on 4) The method of claim 4, wherein the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 5. ### Claim 7 (depends on 4) The method of claim 4, wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 4 and the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 5. ### Claim 8 (depends on 7) The method of claim 7, wherein the patient previously received treatment with melphalan, prednisone, dexamethasone, bortezomib, cyclophosphamide, lenalidomide, doxorubicin, autologous transplant or a combination thereof. ### Claim 9 A method of independently treating peripheral neuropathy in a patient with AL amyloidosis, comprising administering an effective dosage of an antibody which competes for binding to human amyloid A peptide with antibody 2A4 (ATCC Accession Number 9662), wherein: (a) the patient presents with peripheral neuropathy; (b) the patient has not shown any cardiac response to such dosage when previously administered; (c) the patient has not shown any renal response to such dosage when previously administered; (d) the patient previously received treatment with a different agent that did not affect the patient's peripheral neuropathy; and/or (e) the patient is receiving treatment with a different agent that does not affect the patient's peripheral neuropathy. ### Claim 10 (depends on 9) The method of claim 9, wherein the different agent is melphalan, prednisone, dexamethasone, bortezomib, cyclophosphamide, lenalidomide, or a combination thereof. ### Claim 11 (depends on 9) The method of claim 9, wherein the patient presented with a symptom other than peripheral neuropathy. ### Claim 12 (depends on 9) The method of claim 9, wherein the patient presented with peripheral neuropathy. ### Claim 13 (depends on 9) The method of claim 9, wherein the patient has not shown any cardiac or renal response to such dosage when previously administered. ### Claim 14 (depends on 1, 9) The method of claim 1 or 9, wherein the effective dosage of the antibody is administered as a pharmaceutical formulation comprising: a) the antibody at a concentration within the range from about 1 mg/mL to about 100 mg/mL; b) histidine buffer at a concentration within the range from about 20 mM to about 30 mM; c) trehalose at a concentration within the range from about 210 mM to about 250 mM; and d) polysorbate 20 at a concentration within the range from about 0.005% to about 0.05% by weight; and wherein the pharmaceutical formulation is characterized by a pH within the range from about 6 to about 7. ### Claim 15 (depends on 13) The method of claim 13, wherein the dosage is from about 0.5 mg/kg to about 30 mg/kg and the antibody is administered intravenously or subcutaneously at a frequency of from about weekly to about quarterly. ### Claim 16 (depends on 14) The method of claim 14, wherein: a) the antibody is present at a concentration of about 50 mg/mL; b) the histidine buffer is present at a concentration of about 25 mM; c) the trehalose is present at a concentration of about 230 mM; d) the polysorbate 20 is present at a concentration of about 0.2 g/L; and wherein the pH is about 6.5. ### Claim 17 (depends on 15) The method of claim 15, wherein the antibody comprises a light chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 6, 7 and 8, and a heavy chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 9, 10 and 11. ### Claim 18 (depends on 16) The method of claim 16, wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 4. ### Claim 19 (depends on 16) The method of claim 16, wherein the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 5. ### Claim 20 (depends on 16) The method of claim 16, wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO:4 and the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 5. ### Claim 21 (depends on 20) The method of claim 20, wherein the dosage is about 24 mg/kg and the antibody is administered intravenously every 28 days. ### Claim 22 (depends on 21) The method of claim 21, wherein the duration of the treatment is at least 9 months. ### Claim 23 (depends on 22) The method of claim 22, wherein the duration of the treatment is at least 12 months. ### Claim 24 (depends on 1, 21) The method of claim 1 or 21, wherein the duration of treatment is effective to achieve or maintain less than a 2-point increase in NIS-LL from baseline. ### Claim 25 (depends on 24) The method of claim 24, wherein the duration is effective to achieve or maintain at least a 10% decrease in NIS-LL from baseline. ### Claim 26 (depends on 25) The method of claim 25, wherein the duration is effective to achieve or maintain at least a 23% decrease in NIS-LL from baseline. ### Claim 27 (depends on 26) The method of claim 26, wherein the duration is effective to achieve or maintain at least a 35% decrease in NIS-LL from baseline. ### Claim 28 (depends on 27) The method of claim 27, wherein the duration is effective to achieve or maintain at least a 50% decrease in NIS-LL from baseline. ### Claim 29 (depends on 28) The method of claim 28, wherein the duration is effective to achieve or maintain at least a 75% decrease in NIS-LL from baseline. ### Claim 30 (depends on 29) The method of claim 29, wherein the duration is effective to achieve or maintain at least a 30% and 300 pg/mL decrease in NT-proBNP. ### Claim 31 (depends on 8, 10, 21) The method of claim 8, 10 or 21, wherein the patient previously received treatment with CRD, PomDex, CyBorD, BMDex, MDex, LDex, CLD or bortezomib. ### Claim 32 (depends on 1, 9) The method of claim 1 or 9, wherein the antibody is a Fab, Fab′, F(ab′)2, F(ab)c, Dab, nanobody or Fv. ### Claim 33 An antibody which competes for binding to human amyloid A peptide with antibody 2A4 (ATCC Accession Number 9662) for use in a method of treating a patient with peripheral neuropathy associated with AL amyloidosis. ### Claim 34 (depends on 33) The antibody for use of claim 33, wherein progression of the peripheral neuropathy is reversed. ### Claim 35 (depends on 33) The antibody for use of claim 33, wherein the antibody or antigen-binding fragment thereof is a humanized version of 2A4. ### Claim 36 (depends on 33) The antibody for use of claim 33, wherein the antibody comprises a light chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 6, 7 and 8, and a heavy chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 9, 10 and 11. ### Claim 37 (depends on 36) The antibody for use of claim 36, wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 4. ### Claim 38 (depends on 36) The antibody for use of claim 36, wherein the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 5. ### Claim 39 (depends on 36) The antibody for use of claim 36, wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 4 and the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 5. ### Claim 40 (depends on 39) The antibody for use of claim 39, wherein the patient previously received treatment with melphalan, prednisone, dexamethasone, bortezomib, cyclophosphamide, lenalidomide, doxorubicin, autologous transplant or a combination thereof. ### Claim 41 An antibody which competes for binding to human amyloid A peptide with antibody 2A4 (ATCC Accession Number 9662) for use in a method independently treating peripheral neuropathy in a patient with AL amyloidosis, wherein: (a) the patient presents with peripheral neuropathy; (b) the patient has not shown any cardiac response to such dosage when previously administered; (c) the patient has not shown any renal response to such dosage when previously administered; (d) the patient previously received treatment with a different agent that did not affect the patient's peripheral neuropathy; and/or (e) the patient is receiving treatment with a different agent that does not affect the patient's peripheral neuropathy. ### Claim 42 (depends on 41) The antibody for use of claim 41, wherein the different agent is melphalan, prednisone, dexamethasone, bortezomib, cyclophosphamide, lenalidomide, or a combination thereof. ### Claim 43 (depends on 41) The antibody for use of claim 41, wherein the patient presented with a symptom other than peripheral neuropathy. ### Claim 44 (depends on 41) The antibody for use of claim 41, wherein the patient presented with peripheral neuropathy. ### Claim 45 (depends on 41) The antibody for use of claim 41, wherein the patient has not shown any cardiac or renal response to a previous administration of the antibody. ### Claim 46 (depends on 33, 41) The antibody for use of claim 33 or 41, formulated as a pharmaceutical formulation comprising: a) the antibody at a concentration within the range from about 1 mg/mL to about 100 mg/mL; b) histidine buffer at a concentration within the range from about 20 mM to about 30 mM; c) trehalose at a concentration within the range from about 210 mM to about 250 mM; and d) polysorbate 20 at a concentration within the range from about 0.005% to about 0.05% by weight; and wherein the pharmaceutical formulation is characterized by a pH within the range from about 6 to about 7. ### Claim 47 (depends on 46) The antibody for use of claim 46, comprising a dosage from about 0.5 mg/kg to about 30 mg/kg and wherein the antibody is administered intravenously or subcutaneously at a frequency of from about weekly to about quarterly. ### Claim 48 (depends on 47) The antibody for use of claim 47, wherein: a) the antibody is present at a concentration of about 50 mg/mL; b) the histidine buffer is present at a concentration of about 25 mM; c) the trehalose is present at a concentration of about 230 mM; d) the polysorbate 20 is present at a concentration of about 0.2 g/L; and wherein the pH is about 6.5. ### Claim 49 (depends on 48) The antibody for use of claim 48, wherein the antibody comprises a light chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 6, 7 and 8, and a heavy chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 9, 10 and 11. ### Claim 50 (depends on 49) The antibody for use of claim 49, wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 4. ### Claim 51 (depends on 49) The antibody for use of claim 49, wherein the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 5. ### Claim 52 (depends on 49) The antibody for use of claim 49, wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO:4 and the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 5. ### Claim 53 (depends on 52) The antibody for use of claim 52, wherein the dosage is about 24 mg/kg and the antibody is administered intravenously every 28 days. ### Claim 54 (depends on 53) The antibody for use of claim 53, wherein the duration of the treatment is at least 9 months. ### Claim 55 (depends on 54) The antibody for use of claim 54, wherein the duration of the treatment is at least 12 months. ### Claim 56 (depends on 33, 53) The antibody for use of claim 33 or 53, wherein the duration of treatment is effective to achieve or maintain less than a 2-point increase in NIS-LL from baseline. ### Claim 57 (depends on 56) The antibody for use of claim 56, wherein the duration is effective to achieve or maintain at least a 10% decrease in NIS-LL from baseline. ### Claim 58 (depends on 57) The antibody for use of claim 57, wherein the duration is effective to achieve or maintain at least a 23% decrease in NIS-LL from baseline. ### Claim 59 (depends on 58) The antibody for use of claim 58, wherein the duration is effective to achieve or maintain at least a 35% decrease in NIS-LL from baseline. ### Claim 60 (depends on 59) The antibody for use of claim 59, wherein the duration is effective to achieve or maintain at least a 50% decrease in NIS-LL from baseline. ### Claim 61 (depends on 60) The antibody for use of claim 60, wherein the duration is effective to achieve or maintain at least a 75% decrease in NIS-LL from baseline. ### Claim 62 (depends on 61) The antibody for use of claim 61, wherein the duration is effective to achieve or maintain at least a 30% and 300 pg/mL decrease in NT-proBNP. ### Claim 63 (depends on 40, 42, 53) The antibody for use of claim 40, 42 or 53, wherein the patient previously received treatment with CRD, PomDex, CyBorD, BMDex, MDex, LDex, CLD or bortezomib. ### Claim 64 (depends on 33, 41) The antibody for use of claim 33 or 41, wherein the antibody is a Fab, Fab′, F(ab′)2, F(ab)c, Dab, nanobody or Fv. ### Claim 65 Use of an antibody which competes for binding to human amyloid A peptide with antibody 2A4 (ATCC Accession Number 9662) in a method of treating a patient with peripheral neuropathy associated with AL amyloidosis. ### Claim 66 (depends on 65) The use of claim 65, wherein progression of the peripheral neuropathy is reversed. ### Claim 67 (depends on 65) The use of claim 65, wherein the antibody or antigen-binding fragment thereof is a humanized version of 2A4. ### Claim 68 (depends on 65) The use of claim 65, wherein the antibody comprises a light chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 6, 7 and 8, and a heavy chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 9, 10 and 11. ### Claim 69 (depends on 68) The use of claim 68, wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 4. ### Claim 70 (depends on 68) The use of claim 68, wherein the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 5. ### Claim 71 (depends on 68) The use of claim 68, wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 4 and the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 5. ### Claim 72 (depends on 71) The use of claim 71, wherein the patient previously received treatment with melphalan, prednisone, dexamethasone, bortezomib, cyclophosphamide, lenalidomide, doxorubicin, autologous transplant or a combination thereof. ### Claim 73 Use of an antibody which competes for binding to human amyloid A peptide with antibody 2A4 (ATCC Accession Number 9662) for independently treating peripheral neuropathy in a patient with AL amyloidosis, wherein: (a) the patient presents with peripheral neuropathy; (b) the patient has not shown any cardiac response to such dosage when previously administered; (c) the patient has not shown any renal response to such dosage when previously administered; (d) the patient previously received treatment with a different agent that did not affect the patient's peripheral neuropathy; and/or (e) the patient is receiving treatment with a different agent that does not affect the patient's peripheral neuropathy. ### Claim 74 (depends on 73) The use of claim 73, wherein the different agent is melphalan, prednisone, dexamethasone, bortezomib, cyclophosphamide, lenalidomide, or a combination thereof. ### Claim 75 (depends on 73) The use of claim 73, wherein the patient presented with a symptom other than peripheral neuropathy. ### Claim 76 (depends on 73) The use of claim 73, wherein the patient presented with peripheral neuropathy. ### Claim 77 (depends on 73) The use of claim 73, wherein the patient has not shown any cardiac or renal response to such dosage when previously administered. ### Claim 78 (depends on 65, 73) The use of claim 65 or 73, wherein the antibody is administrable as a pharmaceutical formulation comprising: a) the antibody at a concentration within the range from about 1 mg/mL to about 100 mg/mL; b) histidine buffer at a concentration within the range from about 20 mM to about 30 mM; c) trehalose at a concentration within the range from about 210 mM to about 250 mM; and d) polysorbate 20 at a concentration within the range from about 0.005% to about 0.05% by weight; and wherein the pharmaceutical formulation is characterized by a pH within the range from about 6 to about 7. ### Claim 79 (depends on 78) The use of claim 78, comprising a dosage from about 0.5 mg/kg to about 30 mg/kg and wherein the antibody is administered intravenously or subcutaneously at a frequency of from about weekly to about quarterly. ### Claim 80 (depends on 78) The use of claim 78, wherein: a) the antibody is present at a concentration of about 50 mg/mL; b) the histidine buffer is present at a concentration of about 25 mM; c) the trehalose is present at a concentration of about 230 mM; d) the polysorbate 20 is present at a concentration of about 0.2 g/L; and wherein the pH is about 6.5. ### Claim 81 (depends on 79) The use of claim 79, wherein the antibody comprises a light chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 6, 7 and 8, and a heavy chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 9, 10 and 11. ### Claim 82 (depends on 81) The use of claim 81, wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 4. ### Claim 83 (depends on 81) The use of claim 81, wherein the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 5. ### Claim 84 (depends on 81) The use of claim 81, wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO:4 and the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 5. ### Claim 85 (depends on 84) The use of claim 84, wherein the dosage is about 24 mg/kg and the antibody is administered intravenously every 28 days. ### Claim 86 (depends on 85) The use of claim 85, wherein the duration of the treatment is at least 9 months. ### Claim 87 (depends on 86) The use of claim 86, wherein the duration of the treatment is at least 12 months. ### Claim 88 (depends on 65, 85) The use of claim 65 or 85, wherein the duration of treatment is effective to achieve or maintain less than a 2-point increase in NIS-LL from baseline. ### Claim 89 (depends on 88) The use of claim 88, wherein the duration is effective to achieve or maintain at least a 10% decrease in NIS-LL from baseline. ### Claim 90 (depends on 89) The use of claim 89, wherein the duration is effective to achieve or maintain at least a 23% decrease in NIS-LL from baseline. ### Claim 91 (depends on 90) The use of claim 90, wherein the duration is effective to achieve or maintain at least a 35% decrease in NIS-LL from baseline. ### Claim 92 (depends on 91) The use of claim 91, wherein the duration is effective to achieve or maintain at least a 50% decrease in NIS-LL from baseline. ### Claim 93 (depends on 92) The use of claim 92, wherein the duration is effective to achieve or maintain at least a 75% decrease in NIS-LL from baseline. ### Claim 94 (depends on 93) The use of claim 93, wherein the duration is effective to achieve or maintain at least a 30% and 300 pg/mL decrease in NT-proBNP. ### Claim 95 (depends on 72, 74, 85) The use of claim 72, 74 or 85, wherein the patient previously received treatment with CRD, PomDex, CyBorD, BMDex, MDex, LDex, CLD or bortezomib. ### Claim 96 (depends on 65, 73) The use of claim 65 or 73, wherein the antibody is a Fab, Fab′, F(ab′)2, F(ab)c, Dab, nanobody or Fv. ### Claim 97 Use of an antibody which competes for binding to human amyloid A peptide with antibody 2A4 (ATCC Accession Number 9662) in the manufacture of a medicament for treating a patient with peripheral neuropathy associated with AL amyloidosis. ### Claim 98 (depends on 97) The use of claim 97, wherein progression of the peripheral neuropathy is reversed. ### Claim 99 (depends on 97) The use of claim 97, wherein the antibody or antigen-binding fragment thereof is a humanized version of 2A4. ### Claim 100 (depends on 97) The use of claim 97, wherein the antibody comprises a light chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 6, 7 and 8, and a heavy chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 9, 10 and 11. ### Claim 101 (depends on 100) The use of claim 100, wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 4. ### Claim 102 (depends on 100) The use of claim 100, wherein the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 5. ### Claim 103 (depends on 100) The use of claim 100, wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 4 and the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 5. ### Claim 104 (depends on 103) The use of claim 103, wherein the patient previously received treatment with melphalan, prednisone, dexamethasone, bortezomib, cyclophosphamide, lenalidomide, doxorubicin, autologous transplant or a combination thereof. ### Claim 105 Use of an antibody which competes for binding to human amyloid A peptide with antibody 2A4 (ATCC Accession Number 9662) in the manufacture of a medicament for independently treating peripheral neuropathy in a patient with AL amyloidosis, wherein: (a) the patient presents with peripheral neuropathy; (b) the patient has not shown any cardiac response to such dosage when previously administered; (c) the patient has not shown any renal response to such dosage when previously administered; (d) the patient previously received treatment with a different agent that did not affect the patient's peripheral neuropathy; and/or (e) the patient is receiving treatment with a different agent that does not affect the patient's peripheral neuropathy. ### Claim 106 (depends on 105) The use of claim 105, wherein the different agent is melphalan, prednisone, dexamethasone, bortezomib, cyclophosphamide, lenalidomide, or a combination thereof. ### Claim 107 (depends on 105) The use of claim 105, wherein the patient presented with a symptom other than peripheral neuropathy. ### Claim 108 (depends on 105) The use of claim 105, wherein the patient presented with peripheral neuropathy. ### Claim 109 (depends on 105) The use of claim 105, wherein the patient has not shown any cardiac or renal response to such dosage when previously administered. ### Claim 110 (depends on 97, 105) The use of claim 97 or 105, wherein the antibody is administrable as a pharmaceutical formulation comprising: a) the antibody at a concentration within the range from about 1 mg/mL to about 100 mg/mL; b) histidine buffer at a concentration within the range from about 20 mM to about 30 mM; c) trehalose at a concentration within the range from about 210 mM to about 250 mM; and d) polysorbate 20 at a concentration within the range from about 0.005% to about 0.05% by weight; and wherein the pharmaceutical formulation is characterized by a pH within the range from about 6 to about 7. ### Claim 111 (depends on 110) The use of claim 110, comprising a dosage from about 0.5 mg/kg to about 30 mg/kg and wherein the antibody is administered intravenously or subcutaneously at a frequency of from about weekly to about quarterly. ### Claim 112 (depends on 110) The use of claim 110, wherein: a) the antibody is present at a concentration of about 50 mg/mL; b) the histidine buffer is present at a concentration of about 25 mM; c) the trehalose is present at a concentration of about 230 mM; d) the polysorbate 20 is present at a concentration of about 0.2 g/L; and wherein the pH is about 6.5. ### Claim 113 (depends on 111) The use of claim 111, wherein the antibody comprises a light chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 6, 7 and 8, and a heavy chain variable region comprising three complementarity determining regions set forth as SEQ ID NOs: 9, 10 and 11. ### Claim 114 (depends on 113) The use of claim 113, wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 4. ### Claim 115 (depends on 113) The use of claim 113, wherein the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 5. ### Claim 116 (depends on 113) The use of claim 113, wherein the light chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 4 and the heavy chain variable region comprises the amino acid sequence set forth as SEQ ID NO: 5. ### Claim 117 (depends on 116) The use of claim 116, wherein the dosage is about 24 mg/kg and the antibody is administered intravenously every 28 days. ### Claim 118 (depends on 117) The use of claim 117, wherein the duration of the treatment is at least 9 months. ### Claim 119 (depends on 118) The use of claim 118, wherein the duration of the treatment is at least 12 months. ### Claim 120 (depends on 97, 117) The use of claim 97 or 117, wherein the duration of treatment is effective to achieve or maintain less than a 2-point increase in NIS-LL from baseline. ### Claim 121 (depends on 120) The use of claim 120, wherein the duration is effective to achieve or maintain at least a 10% decrease in NIS-LL from baseline. ### Claim 122 (depends on 121) The use of claim 121, wherein the duration is effective to achieve or maintain at least a 23% decrease in NIS-LL from baseline. ### Claim 123 (depends on 122) The use of claim 122, wherein the duration is effective to achieve or maintain at least a 35% decrease in NIS-LL from baseline. ### Claim 124 (depends on 123) The use of claim 123, wherein the duration is effective to achieve or maintain at least a 50% decrease in NIS-LL from baseline. ### Claim 125 (depends on 124) The use of claim 124, wherein the duration is effective to achieve or maintain at least a 75% decrease in NIS-LL from baseline. ### Claim 126 (depends on 125) The use of claim 125, wherein the duration is effective to achieve or maintain at least a 30% and 300 pg/mL decrease in NT-proBNP. ### Claim 127 (depends on 104, 106, 117) The use of claim 104, 106 or 117, wherein the patient previously received treatment with CRD, PomDex, CyBorD, BMDex, MDex, LDex, CLD or bortezomib. ### Claim 128 (depends on 97, 105) The use of claim 97 or 105, wherein the antibody is a Fab, Fab′, F(ab′)2, F(ab)c, Dab, nanobody or Fv.