U.S. Serial No. 15/988,944
`Preliminary Amendment
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`WSGR Reference No. 52426-701201
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`AMENDMENTS TO THE CLAIMS
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`This listing of claims will replace all prior versions, and listings, of claims in this
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`application.
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`The following amendments do not constitute an admission regarding the
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`patentability of the amended subject matter and should not be so construed. Applicants reserve
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`the right to pursue the subject matter of the canceled claims in this or any other appropriate
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`patent application.
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`Listing of claims:
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`1.
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`(Original) A modified antibody comprising a formula:
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`A-L-P
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`wherein
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`A is an antibody or antibody fragment that binds to a target antigen,
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`P is a peptide that reduces binding of A to the target antigen at physiological pH
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`and that does not reduce binding of A to the target antigen at acidic pH, and
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`L is a linking moiety that connects A to P at physiological pH and in a tumor
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`microenvironment and L is bound to A outside an antigen binding site.
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`2.
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`3.
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`(Cancelled).
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`(Original) The modified antibody of claim 1, wherein at physiological pH P is
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`reversibly bound to A at or near the antigen binding site.
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`4.
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`(Original) The modified antibody of claim 1, wherein P inhibits the binding of A
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`to the target antigen at physiological pH and P does not inhibit the binding of A to the target
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`antigen at acidic pH.
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`5.
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`(Original) The modified antibody of claim 1, wherein in tissue other than the
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`tumor microenvironment, P sterically blocks A from binding to the target antigen.
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`6.
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`7.
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`(Cancelled).
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`(Original) The modified antibody of claim 1, wherein the modified antibody has
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`an increased binding affinity for the target antigen in the tumor microenvironment compared to
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`the binding affinity of the modified antibody for the target antigen in a non-tumor
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`microenvironment.
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`8.
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`(Original) The modified antibody of claim 1, wherein P comprises a peptide
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`sequence with at least one histidine.
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`U.S. Serial No. 15/988,944
`Preliminary Amendment
`
`WSGR Reference No. 52426-701201
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`9.
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`(Original) The modified antibody of claim 8, wherein the histidine forms a
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`binding interaction at or near the antigen binding site of A at physiological pH.
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`10. — l9. (Cancelled).
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`20.
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`(Original) The modified antibody of claim 8, wherein at acidic pH P is reversibly
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`bound to L.
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`21.
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`(Original) The modified antibody of claim 20, wherein L comprises a peptide
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`sequence with at least one aspartic acid or glutamic acid, or a combination thereof.
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`22.
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`(Original) The modified antibody of claim 21, wherein the histidine of P forms
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`an interaction with the aspartic acid or glutamic acid of L.
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`23. — 39. (Cancelled).
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`40.
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`(Original) The modified antibody of claim 1, wherein A is a full length antibody,
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`a single-chain antibody, an Fab fragment, an Fab’ fragment, an (Fab’)2 fragment, an FV
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`fragment, a divalent single chain antibody, bispecific antibody, a trispecific antibody, a
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`tetraspecific antibody, or an antibody drug conjugate.
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`41. — 49. (Cancelled).
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`50.
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`(Original) The modified antibody of claim 1, wherein the target antigen is
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`CTLA4 and P comprises an amino acid sequence selected from the group consisting of Peptide
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`l, Peptide 2, Peptide 5, Peptide 6, Peptide lO, Peptide l3, Peptide 26, Peptide l4, and Peptide 15.
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`51. — 60. (Cancelled).
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`61.
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`(Original) The modified antibody of claim 1, wherein the target antigen is PD-Ll
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`and P comprises an amino acid sequence selected from the group consisting of Peptide 20,
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`Peptide 27, Peptide 2l, Peptide 22, Peptide 23, Peptide 28, Peptide 29, Peptide 30, Peptide 3 l,
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`and Peptide 24.
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`62. — 76. (Cancelled).
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`77.
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`(Original) The modified antibody of claim 1, wherein P comprises a peptide
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`sequence with at least two histidines.
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`78.
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`79.
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`(Cancelled).
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`(Original) The modified antibody of claim 77, wherein P comprises a peptide
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`sequence with at least two histidines and at least two cysteines.
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`U.S. Serial No. 15/988,944
`Preliminary Amendment
`
`WSGR Reference No. 52426-701201
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`80.
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`(Original) The modified antibody of claim 1, wherein P comprises a peptide
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`sequence with at least two charged amino acid residues wherein the charged amino acid residues
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`are selected from the group consisting of aspartate, glutamate, and histidine.
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`81.
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`82.
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`(Cancelled).
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`(Original) The modified antibody of claim 1, wherein P comprises a peptide
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`sequence with at least three charged amino acid residues wherein the charged amino acid
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`residues are selected from the group consisting of aspartate, glutamate, and histidine.
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`83.
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`84.
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`(Cancelled).
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`(Original) The modified antibody of claim 82, wherein P comprises a peptide
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`sequence with at least one histidine and at least two aspartates.
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`85.
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`(Original) The modified antibody of claim 1, wherein P comprises a peptide
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`sequence with at least one cysteine.
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`86.
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`87.
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`(Cancelled).
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`(Original) The modified antibody of claim 1, wherein P comprises a peptide
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`sequence with at least two cysteine amino acid residues.
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`88.
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`89.
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`(Cancelled).
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`(Original) The modified antibody of claim 87, wherein P comprises a peptide
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`sequence with at least two cysteines and at least three charged amino acid residues wherein the
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`charged amino acid residues are selected from the group consisting of aspartate, glutamate, and
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`histidine.
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`90. — 93. (Cancelled).
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`94.
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`(Original) The modified antibody of claim 1, wherein P does not comprise a
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`lysine or arginine.
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`95.
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`(Original) The modified antibody of claim 1, wherein P comprises at least one
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`histidine and at least one aspartate.
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`96.
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`(Original) The modified antibody of claim 1, wherein P comprises at least one
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`histidine and at least one glutamate.
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`97.
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`(Original) The modified antibody of claim 1, wherein P comprises at least one
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`histidine and at least two glutamates.
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`98.
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`(Original) The modified antibody of claim 1, wherein P comprises at least two
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`histidines and at least one aspartate or at least one glutamate.
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`U.S. Serial No. 15/988,944
`Preliminary Amendment
`
`WSGR Reference No. 52426-701201
`
`99.
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`(Original) The modified antibody of claim 1, wherein P comprises at least one
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`histidine, wherein at least one hydrogen bonding amino acid residue is within two amino acid
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`positions to the histidine, wherein the hydrogen bonding amino acid residue is selected from the
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`group consisting of serine, threonine, tyrosine, asparagine, and glutamine.
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`100. — 105. (Cancelled).
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`106.
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`(Original) The modified antibody of claim 1, wherein A-L-P does not comprise a
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`protease cleavage site that releases A from P in a tumor microenvironment.
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`107.
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`(Original) The modified antibody of claim 1, wherein L comprises a peptide
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`sequence with at least one histidine.
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`108.
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`(Original) The modified antibody of claim 107, wherein at acidic pH L is
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`reversibly bound to P.
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`109.
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`(Original) The modified antibody of claim 108, wherein P comprises a peptide
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`sequence with at least one aspartic acid or glutamic acid, or a combination thereof.
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`110.
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`(Original) The modified antibody of claim 109, wherein the histidine of L forms
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`an interaction with the aspartic acid or glutamic acid of P.
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`111.
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`(Currently Amended) A pharmaceutical composition, comprising:
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`(a) a modified antibody according to anyone-etlel-ai-ms—l—l—l-G claim 1, and
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`(b) a pharmaceutically acceptable excipient.
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