A composition comprising an isolated single domain antibody or fragment thereof that binds to mature human TNF-α,
- wherein the antibody is characterized in that when the antibody binds to TNF-α the induction of endothelial procoagulant activity is inhibited,
- wherein the antibody binds to TNF-α such that the epitope defined by the topographic regions of 1-18 (Val1-Arg2-Ser3-Ser4-Ser5-Arg6-Thr7-Pro8-Ser9-Asp10-Lys11-Pro12-Val13-Ala14-His15-Val16-Val17-Ala18), 58-65 (Ile58-Tyr59-Ser60-Gln61-Val62-Leu63-Phe64-Lys65), 115-125 (Tyr115-Glu116-Pro117-Ile118-Tyr119-Leu120-Gly121-Gly122-Val123-Phe124-Gln125) and 138-149 (Arg138-Pro139-Asp140-Tyr141-Leu142-Asp143-Phe144-Ala145-Glu146-Ser147-Gly148-Gln149), or the topographic region of residues 1-18 (Val1-Arg2-Ser3-Ser4-Ser5-Arg6-Thr7-Pro8-Ser9-Asp10-Lys11-Pro12-Val13-Ala14-His15-Val16-Val17-Ala18) and 108-128 (Gly108-Ala109-Glu110-Ala111-Lys112-Pro113-Trp114-Tyr115-Glu116-Pro117-Ile118-Tyr119-Leu120-Gly121-Gly122-Val123-Phe124-Gln125-Leu126-Glu127-Lys128), or the topographic region of residues 56-79 (Tyr56-Leu57-Ile58-Tyr59-Ser60-Gln61-Val62-Leu63-Phe64-Lys65-Gly66-Gln67-Gly68-Cys69-Pro70-Ser71-Thr72-His73-Val74-Leu75-Leu76-Thr77-His78-Thr79), 110-127 (Glu110-Ala111-Lys112-Pro113-Trp114-Tyr115-Glu116-Pro117-Ile118-Tyr119-Leu120-Gly121-Gly122-Val123-Phe124-Gln125-Leu126-Glu127) and 135-155 (Glu135-Ile136-Asn137-Arg138-Pro139-Asp140-Tyr141-Leu142-Asp143-Phe144-Ala145-Glu146-Ser147-Gly148-Gln149-Val150-Tyr151-Phe152-Gly153-Ile154-Ile155), or the topographic region of residues 1-30 (Val1-Arg2-Ser3-Ser4-Ser5-Arg6-Thr7-Pro8-Ser9-Asp10-Lys11-Pro12-Val13-Ala14-His15-Val16-Val17-Ala18-Asn19-Pro20Gln21 Ala22-Glu23-Gly24-Gln25-Leu26-Gln27-Trp28-Leu29-Asn30), 117-128 (Pro117-Ile118-Tyr119-Leu120-Gly121-Gly122-Val123-Phe124-Gln125-Leu126-Glu127-Lys128) and 141-153 (Tyr141-Leu142-Asp143-Phe144-Ala145-Glu146-Ser147-Gly148-Gln149-Val150-Tyr151-Phe152-Gly153), or the topographic region of residues 22-40 (Ala22-Glu23-Gly24-Gln25-Leu26-Gln27-Trp28-Leu29-Asn30-Arg31-Arg32-Ala33-Asn34-Ala35-Leu36-Leu37-Ala38-Asn39-Gly40), 49-97 (Val49-Val50-Pro51-Ser52-Glu53-Gly54-Leu55-Tyr56-Leu57-Ile58-Tyr59-Ser60-Gln61-Val62-Leu63-Phe64-Lys65-Gly66-Gln67-Gly68-Cys69-Pro70-Ser71-Thr72-His73-Val74-Leu75-Leu76-Thr77-His78-Thr79-Ile80-Ser81-Arg82-Ile83-Ala84-Val85-Ser86-Tyr87-Gln88-Thr89-Lys90-Val91-Asn92-Leu93-Leu94-Ser95-Ala96-Ile97), 110-127 (Glu110-Ala111-Lys112-Pro113-Trp114-Tyr115-Glu116-Pro117-Ile118-Tyr119-Leu120-Gly121-Gly122-Val123-Phe124-Gln125-Leu126-Glu127) and 136-153 (Ile136-Asn137-Arg138-Pro139-Asp140-Tyr141-Leu142-Asp143-Phe144-Ala145-Glu146-Ser147-Gly148-Gln149-Val150-Tyr151-Phe152-Gly153), or the topographic region of residues 1-20 (Val1-Arg2-Ser3-Ser4-Ser5-Arg6-Thr7-Pro8-Ser9-Asp10-Lys11-Pro12-Val13-Ala14-His15-Val16-Val17-Ala18-Asn19-Pro20) and 76-90 (Leu76-Thr77-His78-Thr79-Ile80-Ser81-Arg82-Ile83-Ala84-Val85-Ser86-Tyr87-Gln88-Thr89-Lys90), or the topographic region of residues 22-40 (Ala22-Glu23-Gly24-Gln25-Leu26-Gln27-Trp28-Leu29-Asn30-Arg31-Arg32-Ala33-Asn34-Ala35-Leu36-Leu37-Ala38-Asn39-Gly40), 69-97 (Cys69-Pro70-Ser71-Thr72-His73-Val74-Leu75-Leu76-Thr77-His78-Thr79-Ile80-Ser81-Arg82-Ile83-Ala84-Val85-Ser86-Tyr87-Gln88-Thr89-Lys90-Val91-Asn92-Leu93-Leu94-Ser95-Ala96-Ile97), 105-128 (Thr105-Pro106-Glu107-Gly108-Ala109-Glu110-Ala111-Lys112-Pro113-Trp114-Tyr115-Glu116-Pro117-Ile118-Tyr119-Leu120-Gly121-Gly122-Val123-Phe124-Gln125-Leu126-Glu127-Lys128) and 135-155 (Glu135-Ile136-Asn137-Arg138-Pro139-Asp140-Tyr141-Leu142-Asp143-Phe144-Ala145-Glu146-Ser147-Gly148-Gln149-Val150-Tyr151-Phe152-Gly153-Ile154-Ile155) is prevented from binding to mature human TNF-α receptor.