INFLUENZA NEUTRALIZING AGENTS

1 . A method of identifying a potential influenza virus neutralizing agent, which agent mimics the binding site of an influenza virus A neutralizing molecule, wherein said molecule comprises one, two, or three hypervariable region sequences from a heavy chain selected from the group consisting of SEQ ID NO: 7, SEQ ID NO: 8, and SEQ ID NO: 9, or a functionally active fragment thereof, the method comprising

(a) employing the variant amino acid sequences of at least one heavy chain hypervariable region sequence in rational drug design to design a potential influenza virus neutralizing agent which mimics the neutralizing molecule; and

(b) contacting said potential influenza virus neutralizing agent from step (a) with an influenza virus to determine its capacity to act as a neutralizing agent.

2 . The method of claim 1 , wherein

(a) the agent mimics a qualitative activity of the neutralizing antibody;

(b) the hypervariable region sequence of (a) comprises a sequence selected from the group consisting of SEQ ID NO: 7; SEQ ID NO: 8, and SEQ ID NO: 9;

(c) the neutralizing agent is a Surrobody, an influenza neutralizing antibody, antibody fragment, peptide mimetic, a fusion protein, an immunoadhesin, or a small molecule; or

(d) the neutralizing molecule is a C05 antibody.

3 . The method of claim 2 , wherein the agent has the ability to bind influenza virus.

4 - 8 . (canceled)

9 . The method of claim 2 , wherein the agent is a Surrobody, an influenza neutralizing antibody, or an antibody fragment, and comprises at least one heavy chain hypervariable region having an extended amino acid sequence as compared to its germline sequence.

10 . The method of claim 9 , wherein the at least one heavy chain hypervariable region is (a) HVR-H1, (b) HVR-H3, or (c) HVR-H1 and HVR-H3.

11 - 12 . (canceled)

13 . The method of claim 10 , wherein

(a) the HVR-H1 extended amino acid sequence comprises about 1 to about 5 amino acids; and/or

(b) the HVR-H3 extended amino acid sequence comprises about 1 to about 20 amino acids.

14 . (canceled)

15 . The method of claim 13 , wherein the extended amino acid sequence is GESTL (SEQ ID NO:30), or a variant thereof.

16 . The method of claim 13 , wherein the HVR-H3 extended amino acid sequence is

(a) HMSMQQVVSAGWERADLVGD (SEQ ID NO:31), or a variant thereof or

(b) a variant of SEQ ID NO:9.

17 - 22 . (canceled)

23 . An influenza virus neutralizing molecule comprising

a) at least one HVR sequence selected from the group consisting of:

(SEQ ID NO: 7)

(i)

HVR-H1 comprising GESTLSYYAVS;

(SEQ ID NO: 8)

(ii)

HVR-H2 comprising WLSIINAGGGDID;

(SEQ ID NO: 9)

(iii)

HVR-H3 comprising AKHMSMQQVVSAGWERADLVGDAFD,

and

b) at least one variant HVR, wherein the HVR comprises modification of at least one residue of the sequence depicted in SEQ ID NOS: 7, 8, or 9.

24 . The neutralizing molecule of claim 23 , wherein

(a) G in a variant HVR-H1 is A;

(b) the first Y in a variant HVR-H1 is F; or

(c) the neutralizing molecule further comprises a surrogate light chain.

25 . (canceled)

26 . The neutralizing molecule of claim 23 , further comprising at least one HVR sequence selected from the group consisting of:

(SEQ ID NO: 13)

(i)

IGAGYDVHWY;

(SEQ ID NO: 14)

(ii)

LLIYDNNNRP;

(SEQ ID NO: 15)

(iii)

QSYDNSLSGS;

(SEQ ID NO: 16)

(iv)

IRKFLNWY;

(SEQ ID NO: 17)

(v)

LLIYDASNLQ;

(SEQ ID NO: 18)

(vi)

QQYDGLPF;

(SEQ ID NO: 19)

(vii)

IRNSLNWY;

(SEQ ID NO: 20)

(viii)

LLIHDASNLE;

and

(SEQ ID NO: 21)

(ix)

QQANSFPL.

27 . (canceled)

28 . The method of claim 1 or 2 , wherein the agent identified is an antibody, and the method further comprises the step of selecting a peptide or polypeptide that functionally mimics a neutralization epitope to which said identified antibody binds.

29 . The method of claim 28 , wherein said identified antibody binds a hemagglutinin (HA) antigen.

30 . The method of claim 28 , wherein the method further comprises the developing a vaccine based upon the selected peptide or polypeptide.

31 . The method of claim 30 , wherein

(a) the vaccine is a synthetic vaccine;

(b) the vaccine comprises (i) an attenuated influenza A virus, or a part thereof; or (ii) a killed influenza A virus, or part thereof;

(c) the vaccine comprises a peptide or polypeptide functionally mimicking a neutralization epitope bound by an antibody that binds a hemagglutinin (HA) antigen selected from an H3 subtype and an H1 subtype; or

(d) the peptides or polypeptides of the vaccine contain antigenic determinants that raise crossreactive influenza A virus neutralizing antibodies.