# US 2020/0399785 A1 · Libraries of genetic packages comprising novel hc cdr3 designs > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 2020/0399785 A1 - Document ID: US20200399785A1 - Status: Published application - Kind: A1 - Application number: 16/897,069 - Filed: 2020-06-09 - Published: 2020-12-24 - Earliest claimed: 2008-03-13 - Assignees: Dyax Corp. - Applicants: Dyax Corp. - Inventors: Robert Charles Ladner - Web page: https://patentgrep.com/patent/US20200399785A1 ## CPC - C40B 50/06: Biochemical methods, e.g. using enzymes or whole viable microorganisms - C07K 16/005: {constructed by phage libraries} - C07K 16/1275: Streptococcus (G) - C07K 16/28: against receptors, cell surface antigens or cell surface determinants - C40B 40/08: Libraries containing RNA or DNA which encodes proteins, e.g. gene libraries - C07K 2317/565: Complementarity determining region [CDR] - C40B: COMBINATORIAL CHEMISTRY; LIBRARIES, e.g. CHEMICAL LIBRARIES (in silico combinatorial libraries of nucleic acids, proteins or peptides G16B35/00; in silico combinatorial chemistry G16C20/60) - C07K: PEPTIDES (peptides in foodstuffs A23; obtaining protein compositions for foodstuffs, working-up proteins for foodstuffs A23J; preparations for medicinal purposes A61K; peptides containing beta-lactam rings C07D; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, C07D; ergot alkaloids of the cyclic peptide type C07D519/02; macromolecular compounds having statistically distributed amino acid units in their molecules, i.e. when the preparation does not provide for a specific; but for a random sequence of the amino acid units, homopolyamides and block copolyamides derived from amino acids C08G69/00; macromolecular products derived from proteins C08H1/00; preparation of glue or gelatine C09H; single cell proteins, enzymes C12N; genetic engineering processes for obtaining peptides C12N15/00; compositions for measuring or testing processes involving enzymes C12Q; investigation or analysis of biological material G01N33/00) ## Abstract Provided are compositions and methods for preparing and identifying antibodies having CDR3s that vary in sequence and in length from very short to very long which in certain embodiments may bind to a carbohydrate moiety or the active site of an enzyme. Libraries coding for antibodies with the CDR3s are also provided. The libraries can be provided by modifying a pre-existing nucleic acid library. ## Claims ### Claim at position 1 -14. (canceled) ### Claim 15 A method of diversifying a library, the method comprising mutagenizing a focused library of vectors or genetic packages that display, display and express, or comprise a member of a diverse family of human antibody related peptides, polypeptides and proteins and collectively display, display and express, or comprise at least a portion of the diversity of the antibody family, wherein the vectors or genetic packages comprise variegated DNA sequences that encode a heavy chain (HC) CDR3 selected from the group consisting of: (a) a HC CDR3 that is about 3 or about 4 or about 5 amino acids in length; (b) a HC CDR3 that is about 23, about 24, about 25, about 26, about 27, about 28, about 29, about 30, about 31, about 32, about 33, about 34 or about 35 amino acids in length (e.g., about 23 to about 35 amino acids in length); and c) a HC CDR3 that is from about 6 to about 20 amino acids in length, wherein the HC CDR3 comprises amino acids from a diversified D region or fragment thereof or an extended JH region. ### Claim 16 (depends on 15) The method of claim 15, wherein the mutagenizing comprises error-prone PCR. ### Claim 17 (depends on 15) The method of claim 15, wherein the mutagenizing comprises wobbling. ### Claim 18 (depends on 15) The method of claim 15, wherein the mutagenizing comprises dobbling. ### Claim 19 (depends on 15) The method of claim 15, wherein the mutagenizing introduces on average about 1 to about 10 mutations per HC CDR3. ### Claim 20 (depends on 15) The method of claim 15, wherein the HC CDR3 is enriched in Tyr (Y) and Ser (S). ### Claim 21 (depends on 15) The method of claim 15, wherein the library comprises a D region or a fragment of a D region. ### Claim 22 (depends on 21) The method of claim 21, wherein the D region is selected from the group consisting of D2-2(RF 2), D2-8(RF 2), D2-15(RF 2), D2-21(RF 2), D3-16(RF 2), D3-22 (RF 2), D3-3 (RF-2), D3-9 (RF 2), D3-10 (RF 2), D1-26 (RF 3), D4-11 (RF 2), D4-4 (RF 2), D5-5 (RF 3), D5-12 (RF 3), D5-18 (RF 3), D6-6 (RF1), D6-13 (RF 1), and D6-19 (RF 1). ### Claim 23 (depends on 21) The method of claim 21, wherein the D region comprises one or more cysteine (Cys) residues and the one or more Cys residues are held constant. ### Claim 24 (depends on 21) The method of claim 21, wherein the HC CDR3 comprises one or more filling codons between FR3 and the D region and each filling codon is individually NNK, TMY, TMT, or TMC. ### Claim 25 (depends on 21) The method of claim 21, wherein the HC CDR3 comprises one or more filling codons between the D region and JH and each filling codon is individually NNK, TMY, TMT, or TMC. ### Claim 26 (depends on 15) The method of claim 15, wherein the library further comprises a HC CDR1, HC CDR2, or a light chain and comprises diversity in the HC CDR1, HC CDR2, or light chain. ### Claim 27 A method of diversifying a library, the method comprising mutagenizing a library comprising a HC CDR3 that is 3, 4, or 5 amino acids in length, wherein the CDR3 comprises amino acids from a JH region or from a D region joined to the FR4 portion of a JH region. ### Claim 28 (depends on 27) The method of claim 27, wherein the HC CDR3 is from a D region joined to the FR4 portion of a JH region and comprises a trimer, a tetramer, or a pentamer, wherein the trimer, tetramer, or pentamer does not comprise a cysteine residue. ### Claim 29 (depends on 27) The method of claim 27, wherein the HC CDR3 is from a D region joined to the FR4 portion of a JH region and comprises a trimer, a tetramer, or a pentamer, wherein the trimer, tetramer, or pentamer does not comprise a stop codon. ### Claim 30 (depends on 27) The method of claim 27, wherein the D region comprises a TAG codon and the TAG codon is replaced by a codon selected from the group consisting of TCG, TTG, TGG, CAG, AAG, TAT, and GAG. ### Claim 31 (depends on 27) The method of claim 27, wherein the D region comprises a TAA codon and the TAA codon is replaced by a codon selected from the group consisting of TCA, TTA, CAA, AAA, TAT, and GAA. ### Claim 32 (depends on 27) The method of claim 27, wherein the D region comprises a TGA codon and the TGA codon is replaced by a codon selected from the group consisting of TGG, TCA, TTA, AGA, and GGA.