Vector

A vector comprising a nucleotide sequence encoding an anti-TNF antibody fragment selected from an antigen-binding fragment (Fab), a fragment antibody (F(ab′)2), a single chain antibody (scFv), and a single-domain antibody (sdAb).

The vector according to any preceding claim, wherein the anti-TNF antibody or fragment thereof is any of adalimumab or a fragment thereof, infliximab or a fragment thereof, golimumab or a fragment thereof, or certolizumab or a fragment thereof.

The vector according to any preceding claim, wherein the anti-TNF antibody or fragment thereof is adalimumab or a fragment thereof, or infliximab or a fragment thereof.

The vector according to any preceding claim, wherein the anti-TNF antibody or fragment thereof is adalimumab or a fragment thereof.

The vector according to any preceding claim, wherein the anti-TNF antibody or fragment thereof is an antigen-binding fragment (Fab).

The vector according to any preceding claim, wherein the anti-TNF antibody or fragment thereof is an antigen binding fragment (Fab) of adalimumab.

The vector according to any preceding claim, wherein the anti-TNF antibody or fragment thereof comprises one or more CDR regions selected from SEQ ID NOs:

• 1 to 6 or derivatives thereof comprising one amino acid substitution.

The vector according to any preceding claim, wherein the anti-TNF antibody or fragment thereof comprises CDR regions HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3 comprising or consisting of SEQ ID NOs:

• 1, 2, 3, 4, 5 and 6 respectively or derivatives thereof comprising one amino acid substitution.

The vector according to any preceding claim, wherein the anti-TNF antibody or fragment thereof comprises a heavy chain comprising or consisting of a sequence with at least 70% identity to SEQ ID NO:

• 7 and/or a light chain comprising or consisting of a sequence with at least 70% identity to SEQ ID NO:
• 8.

The vector according to any preceding claim, wherein the nucleotide sequence encoding an anti-TNF antibody or a fragment encodes a heavy chain comprising or consisting of a sequence with at least 70% identity to SEQ ID NO:

• 7, a 2A self-cleaving peptide having at least 70% sequence identity to any of SEQ ID NOs:
• 55-58, and a light chain comprising or consisting of a sequence with at least 70% identity to SEQ ID NO:
• 8.

The vector according to any preceding claim, wherein the nucleotide sequence encoding an anti-TNF antibody or a fragment thereof comprises or consists of a nucleotide sequence having at least 70% identity to SEQ ID NO:

• 66.

The vector according to any preceding claim, wherein the vector comprises a nucleotide sequence having at least 70% identity to SEQ ID NO:

• 77.

The vector according to any preceding claim, wherein the nucleotide sequence encoding the anti-TNF antibody or a fragment thereof is operably linked to a polyadenylation sequence, optionally wherein the polyadenylation sequence is selected from any of:

• a bovine growth hormone (bGH) polyadenylation sequence, a SV40 polyadenylation sequence, and a rabbit beta-globin polyadenylation sequence.

The vector according to any preceding claim, wherein the nucleotide sequence encoding the anti-TNF antibody or a fragment thereof is operably linked to a woodchuck hepatitis post-transcriptional regulatory element (WPRE).

The vector according to any preceding claim, wherein the nucleotide sequence encoding the anti-TNF antibody or a fragment thereof is operably linked to an intron, optionally wherein the intron is selected from a beta-globin intron or a SV40 intron.

The vector according to any previous claim, wherein the vector is a viral vector.

The vector according to any previous claim, wherein the vector is any of a parvoviral vector, an adenoviral vector, a herpes simplex viral vector, an anelloviral vector, a retroviral vector or a lentiviral vector, preferably wherein the vector is an adeno-associated virus (AAV) vector.

The vector according to any previous claim, wherein the vector is an AAV vector particle.

The vector according to any previous claim, wherein the vector comprises one or more inverted terminal repeats (ITRs).

The vector according to any previous claim, wherein the vector comprises a nucleotide sequence having at least 70% identity to SEQ ID NO:

• 91.

A vector comprising a nucleotide sequence having at least 70% identity to SEQ ID NO:

• 91.

A vector for use in preventing or treating an inflammatory eye disease, wherein the vector comprises a nucleotide sequence encoding a TNF inhibitor, and wherein the nucleotide sequence encoding the TNF inhibitor is operably linked to an inflammation-inducible promoter.

Use of a vector in the manufacture of a medicament for preventing or treating an inflammatory eye disease, wherein the vector comprises a nucleotide sequence encoding a TNF inhibitor, and wherein the nucleotide sequence encoding the TNF inhibitor is operably linked to an inflammation-inducible promoter.

A method for preventing or treating an inflammatory eye disease, wherein the method comprises administering a vector to a subject in need thereof, wherein the vector comprises a nucleotide sequence encoding a TNF inhibitor, and wherein the nucleotide sequence encoding the TNF inhibitor is operably linked to an inflammation-inducible promoter.