MONOCLONAL ANTIBODIES AGAINST HER2/NEU AND USES THEREOF

1 . An antibody or an antigen-binding fragment that binds specifically to Her2/Neu comprising three variable heavy domain complementarity determining regions (CDR) (CDR H1, H2 and H3) wherein the CDR H1, H2, and H3, comprise an amino acid sequence comprising:

CDR H1: GYSFTSYW (SEQ ID NO:1),

CDR H2: IYPGX 1 X 2 DT, where X 1 is D, E, or Q, X 2 is S, I, or T, and wherein when X 1 is D, X 2 is different than S (SEQ ID NO:2), and

CDR H3: ARHDVGYCTDRTCAKWPEY (SEQ ID NO:3), respectively.

2 . The antibody or the antigen-binding fragment of claim 1 ,

comprising three variable light domain CDR (CDR L1, L2 and L3), wherein the CDR L1, L2, and L3 comprise an amino acid sequence comprising:

CDR L1: SSNIGNNY (SEQ ID NO:4),

CDR L2: DHT (SEQ ID NO:5), and

CDR L3: ASWDYTLSGWV (SEQ ID NO:6), respectively.

3 . The antibody or the antigen-binding fragment of claim 1 , wherein when X 1 is D, X 2 is I, or T.

4 . The antibody or the antigen-binding fragment of claim 1 , wherein when X 1 is E, or Q, X 2 is S.

5 . The antibody or the antigen-binding fragment of claim 1 , wherein X 1 is E and X 2 is S.

6 . The antibody or the antigen-binding fragment of claim 1 , wherein X 1 is Q and X 2 is S.

7 - 8 . (canceled)

9 . The antibody or the antigen-binding fragment of claim 1 , further comprising four variable heavy domain framework regions (HFR)(HFR 1, 2, 3 and 4), wherein said HFR 1, 2, 3, and 4 comprise an amino acid sequence comprising:

HFR1:

(SEQ ID NO: 15)

VQLVQSGAEVKKPGESLKISCKGS,

HFR2:

(SEQ ID NO: 16)

IAWWRQMPGKGLEYMGL,

HFR3:

(SEQ ID NO: 17)

KYSPSFQGQVTISVDKSVSTAYLQWSSLKPSDSAVYFC,

and

HFR4:

(SEQ ID NO: 18)

WGQGTLVTV.

10 . The antibody or the antigen-binding fragment of claim 1 , further comprising four variable light domain framework regions (LFR)(LFR 1, 2, 3 and 4), wherein said LFR 1, 2, 3, and 4 comprise an amino acid sequence, comprising:

LFR1:

(SEQ ID NO: 84)

QSVLTQPPSVSAAPGQKVTISCSGS,

LFR2:

(SEQ ID NO: 85)

VSWYQQLPGTAPKLLIY,

LFR 3: 

(SEQ ID NO: 86)

NRPAGVPDRFSGSKSGTSASLAISGFRSEDEADYYC,

and

LFR4:

(SEQ ID NO: 87)

FGGGTKVTVL.

11 . The antibody or the antigen-binding fragment of claim 1 , comprising a variable heavy domain (V H ) comprising amino acid sequence, comprising:

(SEQ ID NO: 23)

VQLVQSGAEVKKPGESLKISCKGSGYSFTSYWIAVRQMPGKGLEYMGL

IYPGESDTKYSPSFQGQVTISVDKSVSTAYLQWSSLKPSDSAVYFCAR

HDVGYCTDRTCAKWPEYFQHWGQGTLVTV.

12 . The antibody or the antigen-binding fragment of claim 1 , comprising a variable light domain (V L ) comprising amino acid sequence, comprising:

(SEQ ID NO: 83)

QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLL

IYDHTNRPAGVPDRFSGSKSGTSASLAISGFRSEDEADYYCASWDYTL

SGWWFGGGTKVTVL.

13 . The antibody or the antigen-binding fragment of claim 1 , comprising a variable heavy domain (V H ) comprising amino acid sequence, comprising:

(SEQ ID NO: 23)

VQLVQSGAEVKKPGESLKISCKGSGYSFTSYWIAVRQMPGKGLEYMGL

IYPGESDTKYSPSFQGQVTISVDKSVSTAYLQWSSLKPSDSAVYFCAR

HDVGYCTDRTCAKWPEYFQHWGQGTLVTV.

and a variable light domain (V L ) comprising amino acid sequence, comprising:

(SEQ ID NO: 83)

QSVLTQPPSVSAAPGQKVTISCSGSSSNIGNNYVSWYQQLPGTAPKLL

IYDHTNRPAGVPDRFSGSKSGTSASLAISGFRSEDEADYYCASWDYTL

SGWWFGGGTKVTVL.

14 . The antibody or the antigen-binding fragment of claim 1 , wherein the antigen-binding fragment is a single-domain antibody (sdAb), a fragment antigen binding (Fab), a single-chain variable fragment (scFv), or a single-chain fragment antigen binding (scFab).

15 . The antibody or the antigen-binding fragment of claim 1 , wherein the antibody is an IgA, an IgD, an IgE, an IgG, or an IgM.

16 . The antibody or the antigen-binding fragment of claim 15 , wherein the antibody is an IgE.

17 . The antibody or the antigen-binding fragment of claim 1 , wherein the antibody or antigen-binding fragment is humanized or partially humanized.

18 . A compound comprising the antibody or the antigen-binding fragment of claim 1 and a functional moiety.

19 . The compound of claim 18 , wherein the antibody or the antigen-binding fragment is linked to the functional moiety via a peptide linker.

20 . The compound of claim 19 , wherein the antibody or the antigen-binding fragment is functionally linked to the functional moiety via the peptide linker.

21 . The compound of claim 20 , wherein the peptide linker comprises about 3 to about 40 amino acid residues.

22 . The compound of claim 20 , wherein

the peptide linker comprises the amino acid sequence (GGGGS) n or (GGGS) n , wherein n≥1.

23 . The compound of claim 18 , wherein the antibody or the antigen-binding fragment is fused to a second antibody or antigen-binding fragment operable to bind a target epitope.

24 . The compound of claim 18 , wherein the antibody or the antigen-binding fragment is linked to a peptide, a polypeptide, a protein, an enzyme, a second antibody, an antibody fragment, a second antigen-binding fragment or a combination of any two or more thereof; wherein each of the antibody or antigen-binding fragment thereof and the linked peptide, polypeptide, protein, enzyme, second antibody, antibody fragment, second antigen-binding fragment, or the combination of any two or more thereof is functional.

25 . The compound of claim 24 , wherein the antibody fragment is a fragment crystallizable (Fc) region.

26 . A composition, comprising the antibody or the antigen-binding fragment of claim 1 and a pharmaceutically acceptable diluent, carrier, or excipient.

27 - 29 . (canceled)

30 . A method of treating a Her2/Neu associated disease, comprising: administering the antibody or the antigen-binding fragment of claim 1 to a subject in need thereof.

31 . The method of claim 30 , wherein the Her2/Neu associated disease is a cancer.

32 . The method of claim 31 , wherein the cancer is ovarian cancer, breast cancer, stomach cancer, lung cancer, uterine cancer, salivary gland cancer, testicular germ cell cancer, bladder cancer, pancreatic cancer, and esophageal cancer.

33 - 41 . (canceled)