LINKERS, DRUG LINKERS AND CONJUGATES THEREOF AND METHODS OF USING THE SAME

1 - 27 . (canceled)

28 . A conjugate represented by the formula:

Targeting Unit-Linker-Drug Unit,

or a pharmaceutically acceptable salt thereof,

wherein the Targeting unit is selected from an anti-FOLR1 antibody or an antigen-binding portion thereof;

wherein the Linker has the following formula (I):

L1-(AA) s -L2   (I)

wherein:

(i) L1 is a Stretcher unit attached to the Targeting unit,

(ii) AA is an Amino Acid unit having from 1 to 12 subunits;

(iii) s is 0 or 1;

(iv) L2 is a Linker Subunit attached to the Drug unit, wherein the Linker Subunit is a cleavable linker unit that comprises a cleavable peptide;

(v) Drug unit is selected from a cytotoxic agent, an immune modulatory agent, a nucleic acid, a growth inhibitory agent, a PROTAC, a toxin, a radioactive isotope and a chelating ligand; and

(vi) at least one PEG unit,

wherein the at least one PEG unit is present within the Amino Acid unit, the Linker Subunit, or combinations thereof, and wherein the at least one PEG unit has the formula:

each R 76 is independently H, acetyl, —P(═O)(OH) 2 , or —(CH 2 ) v S(═O) 2 (OH);

each q is independently 1-26;

each m is independently 1 to 4;

each n is independently 1 to 4;

each v is independently 1 to 6; and

each *indicates an attachment site for a subunit of the Linker Subunit, Amino Acid unit, or both.

29 . The conjugate of claim 28 , wherein the Stretcher unit is

wherein R 17 is C 1 -C 8 alkylene-C(O)—.

30 . The conjugate of claim 29 , wherein R 17 is C 5 alkylene-C(O)—.

31 . The conjugate of claim 28 , wherein the at least one PEG unit has the formula:

32 . The conjugate of claim 31 , wherein the at least one PEG unit has the formula:

33 . The conjugate of claim 28 , wherein q is independently 4-16.

34 . The conjugate of claim 28 , wherein q is 12.

35 . The conjugate of claim 28 , wherein m is 4.

36 . The conjugate of claim 28 , wherein n is 1.

37 . The conjugate of claim 28 , wherein s is 0.

38 . The conjugate of claim 28 , wherein the cleavable peptide comprises a valine-citrulline peptide, a valine-alanine peptide, a valine-lysine peptide, a phenylalanine-lysine peptide, or a glycine-glycine-phenylalanine-glycine peptide.

39 . The conjugate of claim 28 , wherein the cleavable peptide comprises a Lys (PEG)-valine-citrulline peptide, a valine-Cit(PEG)peptide, a Lys(PEG)-valine-lysine peptide, a valine-lysine(PEG) peptide, a Lys(PEG)-valine-alanine peptide, a Lys(PEG)-phenylalanine-lysine peptide, a phenylalanine-Lys(PEG) peptide or a Lys(PEG)-glycine-glycine-phenylalanine-glycine peptide, wherein Lys(PEG) and Cit(PEG) comprise a PEG unit attached to a lysine residue or a citrulline residue, respectively, wherein the PEG unit is represented by Formula (XVIb).

40 . The conjugate of claim 28 , wherein the cleavable peptide is attached to the Drug unit via a p-amino-benzyloxycarbonyl self immolative group.

41 . The conjugate of claim 28 , wherein s is 1.

42 . The conjugate of claim 28 , wherein the subunits of the Amino Acid unit are selected from alanine, arginine, aspartic acid, asparagine, histidine, glycine, glutamic acid, glutamine, phenylalanine, lysine, leucine, serine, tyrosine, threonine, isoleucine, proline, tryptophan, valine, ornithine, penicillamine, β-alanine, aminoalkanoic acid, aminoalkanoic acid, amino alkanedioic acid, aminobenzoic acid, amino-heterocyclo-alkanoic acid, heterocyclo-carboxylic acid, citrulline, and diaminoalkanoic acid; wherein the at least one PEG unit is attached to one of the subunits.

43 . The conjugate of claim 28 , wherein the conjugate has an average drug loading (p load ) from about 1 to about 8.

44 . The conjugate of claim 43 , wherein the conjugate has an average drug loading (p load ) of about 8.

45 . The conjugate of claim 44 , wherein the conjugate is selected from:

and Ab is the Targeting unit and n is the p load .

46 . The conjugate of claim 28 , wherein the Targeting unit comprises a heavy chain variable (VH) region and a light chain variable (VL) region, the VH region comprising complementarity determining regions HCDR1, HCDR2 and HCDR3, and the VL region comprising LCDR1, LCDR2 and LCDR3, wherein (a) the HCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 30 or 36, (b) the HCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 31, (c) the HCDR3 comprises the amino acid sequence set forth in SEQ ID NO: 32 or 37, (d) the LCDR1 comprises the amino acid sequence set forth in SEQ ID NO: 33 or 38, (e) the LCDR2 comprises the amino acid sequence set forth in SEQ ID NO: 34 or 39, and (f) the LCDR3 comprises the amino acid sequence set forth in SEQ ID NO: 35 or 40.

47 . The conjugate of claim 46 , wherein the VH and VL regions have amino acid sequences that are selected from:

a. VH: SEQ ID NO:6 and VL: SEQ ID NO: 6;

b. VH: SEQ ID NO:8 and VL: SEQ ID NO: 8;

c. VH: SEQ ID NO: 10 and VL: SEQ ID NO: 11;

d. VH: SEQ ID NO: 12 and VL: SEQ ID NO: 13;

e. VH: SEQ ID NO: 14 and VL: SEQ ID NO: 15;

f. VH: SEQ ID NO: 16 and VL: SEQ ID NO: 17;

g. VH: SEQ ID NO: 18 and VL: SEQ ID NO: 19;

h. VH: SEQ ID NO:20 and VL: SEQ ID NO:21;

i. VH: SEQ ID NO:22 and VL: SEQ ID NO:23;

j. VH: SEQ ID NO:24 and VL: SEQ ID NO:25;

k. VH: SEQ ID NO:26 and VL: SEQ ID NO:27; and

l. VH: SEQ ID NO:28 and VL: SEQ ID NO:29;

wherein the VH and VL regions comprise framework regions that are optionally modified with from 1 to 8 amino acid substitutions, deletions or insertions.

48 . The conjugate of claim 46 , wherein the VH and VL regions have amino acid sequences that are selected from:

a. VH: SEQ ID NO:6 and VL: SEQ ID NO:6;

b. VH: SEQ ID NO:8 and VL: SEQ ID NO:8;

c. VH: SEQ ID NO:10 and VL: SEQ ID NO:11;

d. VH: SEQ ID NO:12 and VL: SEQ ID NO:13;

e. VH: SEQ ID NO:14 and VL: SEQ ID NO:15;

f. VH: SEQ ID NO:16 and VL: SEQ ID NO:17;

g. VH: SEQ ID NO:18 and VL: SEQ ID NO:19;

h. VH: SEQ ID NO:20 and VL: SEQ ID NO:21;

i. VH: SEQ ID NO:22 and VL: SEQ ID NO:23;

j. VH: SEQ ID NO:24 and VL: SEQ ID NO:25;

k. VH: SEQ ID NO:26 and VL: SEQ ID NO:27; and

l. VH: SEQ ID NO:28 and VL: SEQ ID NO:29.

49 . The conjugate of claim 46 , wherein the VH and VL regions have amino acid sequences that are selected from:

a. VH: SEQ ID NO: 8 and VL: SEQ ID NO:9;

b. VH: SEQ ID NO:12 and VL: SEQ ID NO:13; and

c. VH: SEQ ID NO:26 and VL: SEQ ID NO:27.

50 . The conjugate of claim 46 , wherein VH and VL regions comprise human framework regions.

51 . The conjugate of claim 46 , wherein the Targeting unit is a monoclonal antibody.

52 . The conjugate of claim 46 , wherein the Targeting unit further comprises a heavy chain constant region.

53 . The conjugate of claim 52 , wherein the heavy chain constant region is of the IgG isotype.

54 . A pharmaceutical composition comprising a conjugate of claim 28 and a pharmaceutically acceptable excipient.

55 . A method of treating a subject with a cancer or an autoimmune disease, comprising administering to the subject in need thereof a conjugate of claim 28 .