IN THE UNITED BTITIE PATENT AND TRRDEHARK OFFICE
`
`§EBIlEIEBIE_flI_Ha1LlH§
`
`I hereby certify that this Rasponsu to Oflics Action and the documents referred to as tnclosod therein are
`being deposited with the United States Postal Sarvica on the data indlcatud bllaw with sufficiunt postage as
`first Class Mal]. in an I'IIVI}.D'pO addressed to:
`Commissioner of Patents and Trademarks. Washington. D.C.
`20231.
`
`,..—...__x
`
` Donald G. Lewis, R
`
`lsfidéa L [ Q‘i2
`23,535
`Data of Deposit
`
`
`:
`
`In re:
`Title:
`
`TSRI 293.0 Div. If con 00239
`ENCODED COHBINATORIAL CHEMICAL LIBRARIES
`
`Janda, K. at al.
`Inventor:
`05/13/95
`Filing Date:
`Serial Number: 08/665,511
`Examiner:
`Weiss, 3.
`
`H§_.“_.if‘f‘,iE.1'-'»‘M'F3!_'_)
`:JUL
`9 W97
`1FT3'9‘H3C3
`
`Art Unit:
`
`1805
`
`Reflnone:ite_oi£ioe_aeti9n
`
`Commissioner of Patents and Trademarks
`Washington, n.c. 20231
`
`sir:
`
`Responsive to the Office Action, dated 12/06/96, please
`amend the specification and claims as follows:
`
` =
`
`AHINDHENTB
`
`M
`
`Please incorporate the parent CRF disk into the instant
`
`The parent application is USSN 0?/860,445, now U.s.
`application.
`Patent No. 5,573,905.
`
`At the and of the specification, after page 6 ,
`
`lease
`
`insert the following Sequence Listing:
`
`
`
`ILMN EXHIBIT 1026
`ILMN EXHIBIT 1026
`
`
`
`Page 1 of 23
`Page1 of23
`
`
`
`§EBIlEIEBIE_flI_Ha1LlH§
`
`I hereby certify that this Rasponsu to Oflics Action and the documents referred to as tnclosod therein are
`being deposited with the United States Postal Sarvica on the data indlcatud bllaw with sufficiunt postage as
`first Class Mal]. in an I'IIVI}.D'pO addressed to:
`Commissioner of Patents and Trademarks. Washington. D.C.
`20231.
`
`,..—...__x
`
` Donald G. Lewis, R
`
`lsfidéa L [ Q‘i2
`23,535
`Data of Deposit
`
`
`:
`
`In re:
`Title:
`
`TSRI 293.0 Div. If con 00239
`ENCODED COHBINATORIAL CHEMICAL LIBRARIES
`
`Janda, K. at al.
`Inventor:
`05/13/95
`Filing Date:
`Serial Number: 08/665,511
`Examiner:
`Weiss, 3.
`
`H§_.“_.if‘f‘,iE.1'-'»‘M'F3!_'_)
`:JUL
`9 W97
`1FT3'9‘H3C3
`
`Art Unit:
`
`1805
`
`Reflnone:ite_oi£ioe_aeti9n
`
`Commissioner of Patents and Trademarks
`Washington, n.c. 20231
`
`sir:
`
`Responsive to the Office Action, dated 12/06/96, please
`amend the specification and claims as follows:
`
` =
`
`AHINDHENTB
`
`M
`
`Please incorporate the parent CRF disk into the instant
`
`The parent application is USSN 0?/860,445, now U.s.
`application.
`Patent No. 5,573,905.
`
`At the and of the specification, after page 6 ,
`
`lease
`
`insert the following Sequence Listing:
`
`
`
`ILMN EXHIBIT 1026
`ILMN EXHIBIT 1026
`
`
`
`Page 1 of 23
`Page1 of23
`
`
`
`.
`
`...- ..=..
`
`:
`
`g
`
`; ; _ _
`
`SEQUENCE LISTING
`
`(1) GENERAL INFORMATION:
`
`(1) APPLICANT: Lerner, Richard
`Janda, Kim
`Brenner, Sydney
`
`(ii) TITLE OF INVENTION: ENCODED COHBINATORIAL CHEMICAL LIBRARIES
`
`(iii) NUMBER OF SEQUENCES: 22
`
`(iv) CORRESPONDENCE ADDRESS:
`(A) ADDRESSEE: The Scripps Research Institute, Office of
`Patent Counsel
`(B) STREET: 10666 North Torrey Pines Road, TPC B
`(C) CITY: La Jolla
`(D) STATE: CA
`(E) COUNTRY: USA
`(P) ZIP: 92037
`
`(V) COMPUTER READABLE FORM:
`(A) MEDIUM TYPE: Floppy disk
`(3) COMPUTER:
`IBH PC compatible
`(C) OPERATING SYSTEM: PC—DGS/MS~DOS
`(D) SOFTWARE: Patentln Release #l.0, Version #1.25
`
`{vi} CURRENT APPLICATION DATA:
`(A) APPLICATION NUMBER: US OT/860bh5
`(B) FILING DATE: 30-MAR-1992
`(C) CLASSIFICATION:
`
`(viii) ATTORNEYfACENT INFORMATION:
`(A) NAME: Fitting. Thomas
`(B) REGISTRATION NUMBER: 34,153
`(C) REFERENCE/DOCKET NUMBER: T5R5U23P
`
`'(ix) TELECOMHUNICATIUN INFORHATION:
`(A) TELEPHONE: 619-55h—2937
`(B) TELEFAK: 619-SSA-5312
`
`(2)
`
`INFORMATION FOR SEQ ID N021:
`
`(1) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 15 base pairs
`(3) TYPE: nucleic acid
`(C) STRANDEDNESS: single
`(D) TOPOLDGY:
`linear
`
`<23
`
`
`
`Page 2 of 23
`Page 2 of 23
`
`
`
`(ii) MOLECULE TYPE: DNA (genomic)
`
`(iii) HYPUTHETICAL: NO
`
`(iv) AHTI-SENSE: N0
`
`(xi) saqfizncn nzscaxrrzon: gag ID no 1;
`
`ccccccrarr CTTAG
`
`(2)
`
`INFORMATION FOR saq 1n no:2:
`
`(1) ssquzncz CHARACTERISTICS:
`(A) LENGTH: 15 base pairs
`(3) TYPE: nucleic acid
`(a) STRANDEDNESS: single
`cu) TOPOLDGY:
`linear
`
`(ii) MOLECULE TY?E: DNA (genomic)
`
`(111) HYPOIHETiCAL: N0
`
`(iv) ANTI-SENSE: NO
`
`(xi) SEQUENCE DESCRIPTION: saq ID ND:2:
`
`AGCTACTTCC CAAGG
`
`(2)
`
`INFORMATION FOR SEQ ID N023:
`
`(i) SEQUENCE CHARACTERISTICS:
`EA) LENGTH: 13 base pairs
`(B) TYPE: nucleic acid
`{C} STRANDEDNESS: single
`(D) TDPDLOGY:
`linear
`
`(ii) MOLECULE TY?E: DNA (genomic)
`
`(iii) HYPOTHETIGAL: NO
`
`(iv) ANTI-SENSE: ND
`
`(ix) FEATURE:
`(A) NAME/KEY: misc_feature
`(B) LDCATION: 13
`(D) OTHER INFORMATION: /note- “N is Pl
`
`(SEQ ID NO 1)"
`
`(04 fl;W5
`
`
`
`Page 3 of 23
`Page 3 of 23
`
`
`
`13
`
`13
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID NO:3:
`
`GACATGCACA TGN
`
`(2)
`
`INFORMATION FOR SEQ ID N024:
`
`(1) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 13 base pairs
`(3) TYPE: nucleic acid
`(C) STRANDEDNESS: single
`(D) TOPOLOGY:
`linear
`
`(ii) MOLECULE TYPE: DNA (genomic)
`
`(iii) HYPOTHETICAL: ND
`
`(iv) ANTI-SENSE: NO
`
`(ix) FEATURE:
`(A) NAME/KEY: misc_feature
`(3) LOCATION: 13
`(D) OTHER INFORMATION:
`
`/note— “N is P1 (SEQ ID NO 1)"
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID Nozfi:
`
`CACATGACGG TAN
`
`(2) INFORMATION FOR SEQ ID NO:5:
`
`(1) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 13 base pairs
`(B) TYPE: nucleic acid
`(C) STRANDEDNESS: single
`(D) TOPOLOGY:
`linear
`
`(ii) MOLECULE TYPE: DNA (genomic)
`
`(iii) HYPOTHETICAL: NO
`
`(iv) ANTI-SENSE: NO
`
`fix)FmflmR
`(A) NAME/KEY: mi5c_featura
`(5) LOCATION: 13
`(D) OTHER INFORHATION:
`
`/note— "N 15 P1 (SEQ ID NO 1)"
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID NO:5:
`
`
`
`
`
`Page 4 of 23
`Page 4 of 23
`
`
`
`13
`
`13
`
`ACGGTACACA ‘mu
`
`(2)
`
`INFCRHATION FOR SEQ ID R016:
`
`(1) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 13 base pairs
`(3) TYPE: nucleic acid
`(C) STRANDEDNESS: single
`(D) TO?DLDGY:
`linear
`
`(ii) HDLECULE TYPE: DNA (genomic)
`
`(iii) HYPOTHETICAL: N0
`
`(iv) ANTI-SENSE: NO
`
`(m)Fmmmk
`(A) NAME/KEY: misc_feature
`us) mamou: 13
`an arm: INFORMATION: /note- "N is P1 (szq ID no 1)»
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID N0:6:
`
`acsaraaccc TAN
`
`(2)
`
`INFORMATION FOR SEQ ID N0:7t
`
`(1) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 20 base pairs
`(3) TYPE: nucleic acid
`(C) STRANDEDNESS: single
`(D) TGPOLOGY:
`linear
`
`:11) MOLECULE TYPE: DNA (genomic)
`
`(iii) HYPDTHETICAL: N0
`
`(iv) ANTI-SENSE: N0
`
`(ix) FEATURE:
`(A) NAME/KEY: misc_featuIe
`(3) LOCATION:
`1
`(D) OTHER INFORMATION: /note- "N is P2 (SEQ ID NO 2)"
`
`(ix) FEATURE:
`(A) NAME/KEY: mi5c_featu:e
`(B)
`IDCRTION: 20
`(D) OTHER INFORMATION: /note- "N is Pl
`
`(SEQ ID NO 1)"
`
`
`
`
`
`Page 5 of 23
`Page 5 of 23
`
`
`
`20
`
`20
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID N0:7:
`NGACATGCAC ATGCACATGN
`
`(2)
`
`INFORMATION FOR SEQ ID N0:B:
`
`(1) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 20 base pairs
`(B) TYPE: nucleic acid
`(C) STRANDEDNESS: single
`(9) TDPOLOGY:
`linear
`
`(ii) MOLECULE TYPE: DNA (genomic)
`
`(111) HYPOTHETICAL: N0
`
`(iv) ANTI—SENSE: N0
`
`(ix) FEATURE:
`(A) NAHE/KEY: misc_feature
`(B)
`IDCATION:
`1
`(D) OTHER INFORHATION:
`
`/note- "N is P2 (SEQ ID NO 2)"
`
`(ix) FEATURE:
`(A) NAME/KEY: misc_f:ature
`(B) LOCATION: 20
`(D) OTHER INFORMATION: /note- "N is El
`
`(SEQ ID NO 1)“
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID R0:B:
`NCACATGCAC ATGACGGTAN
`
`(2) INFORMATION FOR SEQ ID N019:
`
`(i) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 20 base pairs
`(3) TYPE: nucleic acid
`(C) SIRANDEDNESS: single
`(D) TOPOLDGY:
`linear
`
`(ii) MOLECULE TYPE: DNA {genomic}
`
`[iii] HYPOIHETICAL1 N0
`
`(iv) ANTI—SENSE: NO
`
`(1):) FEATURE:
`(A) NAME/KEY: misc_feature
`(15) LOCATION:
`1
`
`
`
`
`
`Page 6 of 23
`Page 6 of 23
`
`
`
`(D) OTHER INFORMATION: /nute- ‘N is P2 (SEQ ID NO 2)"
`
`( ix) FEATURE:
`(A) NAME/KEY: misc_feature
`(5) LOCATION: 20
`(D) OTHER INFORMATION:
`
`/nntB- “N is P1 (SEQ ID NO 1)”
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID No:9:
`
`NCAC£TGflCG GTACACATCN
`
`(2)
`
`INFORMATION FOR SEQ ID NUEIO:
`
`(1) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 20 base pairs
`(3) TYYEI nucleic acid
`(6) STRANDEDNESS: single
`(D) TDPOLDGY:
`linear
`
`(ii) MOLECULE TYPE: DNA (genomic)
`
`(iii) HYPOTHETICAL: NO
`
`(iv) ANTI-SENSE: NO
`
`20
`
`(ix) FEATURE:
`(A) NAME/KEY: mi5c_feature
`(5) LOCATION:
`1
`(D) OTHER INFORMATION:
`
`/notew “N is P2 (SEQ ID NO 2)"
`
`(ix) FEATURE:
`(A) NAME/KEY: miscwfeature
`(B) LOCATION: 20
`(D) OTHER INFORMATION: /note- "N is El {SEQ ID NO 1)"
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID NO:lO:
`
`NCACATGACG GTAACGGTAN
`
`20
`
`(2)
`
`INFORMATION FOR SEQ ID NO:11;
`
`(i) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 20 base pairs
`(B) TYPE: nucleic acid
`(C) STRANDEDNESS: single
`(D) TOPOLOGY:
`linear
`
`(ii) MOLECULE TYPE: DNA (genomic)
`
`‘-7-
`
`QSES
`
`.
`
`s
`
`(‘t.‘_,.‘
`
`""--..__‘}:J
`
`
`
`Page 7 of 23
`Page 7 of 23
`
`
`
`(111) HYPOTHETICAL: NO
`
`(iv) ANTLSENSE: no
`
`(ix) FEATURE:
`(A) NAME/KEY: misc_feature
`(B)
`IDCATION: 1
`(D) OTHER INFORMATION:
`
`/note- “N is P2 {SEQ ID NO 2)"
`
`(ix) FEATURE:
`(A) NAME/KEY: misc_feature
`(3) LOCATION: 20
`(D) OTHER INFORMATION: /note- “N is P1 (SEQ ID NO 1)"
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID NO:11:
`
`NACGGTACAC ATGCACATGN
`
`(2)
`
`INFORMATION FOR SEQ ID N0:l2:
`
`30
`
`(1) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 20 base pairs
`(B) TYEE: nucleic acid
`(C) STRANDEDNESS: single
`(D) TOPOLOGY:
`linear
`
`(ii) MOLECULE TYPE: DNA (genomic)
`
`(iii) HYPOTHETICAL: NO
`
`(iv) ANTI-SENSE: No
`
`(ix) FEATURE:
`(A) NAME/KEY: m1sc_feature
`(B) LOCATION:
`1
`(D) OTHER INFORMATION:
`
`/note- “N is P2 (SEQ ID NO 2)“
`
`(ix) FEATURE:
`(A) NAME/KEY: miscwfeature
`(3) LOCATION: 20
`(D) OTHER INFORMATION:
`
`/note— "N is F1 (SEQ ID NO 1)”
`
`(xi) SEQUENCE DESCRIFTION: SEQ ID NO:12:
`
`20
`
`NACGGTACAC ATGACGGTAN
`
`(2)
`
`INFORMATION FOR SEQ ID H0213:
`
`‘E’? [W 70
`
`
`
`Page 8 of 23
`Page 8 of 23
`
`
`
`(1) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 20 base pairs
`(E) TYPE: nucleic acid
`(C) STRANDEDNESS: single
`(D) TOPOLDGY:
`linear
`
`(ii) MOLECULE TYPE: DNA (genomic)
`
`(iii) HYPOTHETICAL: N0
`
`(iv) ANTI-SENSE: No
`
`(ix) FEATURE:
`(A) NAME/KEY: misc_feature
`(B) LOCATION:
`1
`(D) OTHER INFORMATION:
`
`/note- "N is P2 (SEQ ID NO 2)”
`
`(ix) FEATURE:
`(A) NAME/KEY: misc_feature
`(3) LOCATION: 20
`(D) OTHER INFORMATION:
`
`/noca- "N is P1 (SEQ ID NO 1)”
`
`(xi) SEQUENCE DESCRIFTION: SEQ ID NO:l3:
`
`20
`
`NACGGTAACG GTACACATGN
`
`(2)
`
`INFORMATION FOR SEQ ID NO:1fi:
`
`(i) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 20 base pairs
`(8) TYPE: nucleic acid
`(c) STRANDEDNESS: single
`(D) TOPOLOGY:
`linear
`
`(ii) MOLECULE TYPE: DNA (genomic)
`
`(111) HYPOTHETICAL: N0
`
`(iv) ANTI-SENSE: NO
`
`(u)Fmmmm
`(A) NAME/KEY: misc_feature
`(3) LOCATION:
`1
`(D) OTHER INFORMATION: /note- "N is P2 (SEQ ID NO 2}"
`
`(fl)FflflRE
`(A) NAME/KEY: misc_feature
`(B) LOCATION: 20
`(D) OTHER INFORMATION:
`
`/nDte- "N is Pl
`
`(SEQ ID NO 1)"
`
`‘I5 M 7/
`
`
`
`Page 9 of 23
`Page 9 of 23
`
`
`
`20
`
`30
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID NO:1h:
`
`NAGGGTAACG GTAACCCTAN
`
`(2)
`
`INFORMATION FOR SEQ ID NO:15:
`
`(i) SEQOENCE CHARACTERISTICS:
`(A) LENGTH: 30 base pairs
`(B) TYPE: nucleic acid
`(C) STRANDEDNESS: single
`(D) TOPOLDGY:
`linear
`
`(ii) MOLECULE TYPE: DNA (genomic)
`
`(iii) HYPOTHETICAL: NO
`
`(iv) ANTI—SENSE: NO
`
`(ix) FEATURE:
`(A) NAME/KEY: misc_feature
`(3) LOCATION:
`(lS”1E)
`(D) OTHER INFORMATION: /note- ‘Coding sequence located at
`indicated position“
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID NO:15:
`
`AGCTACTTCC CAAGGGGGCC CTATTCTTAG
`
`(2) INFORMATION FOR SEQ ID uo:15:
`(1) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 30 base pairs
`(5) TYPE: nucleic acid
`(C) STRANDEDNESS: single
`(D) TDPOLDGY: linear
`
`(ii) MOLECULE TYPE: DNA (genomic)
`
`(iii) HYPOTHETICAL: N0
`
`(iv) ANTI-SENSE: NO
`
`(ix) FEATURE:
`(A) NAME/KEY: miscwfeature
`(B) LOCATION:
`(15"16)
`/note- “Anticoding sequence located
`{D} OTHER INFORMATION:
`at indicated position“
`
`
`
`
`
`Page 10 of 23
`Page10of23
`
`
`
`10
`
`1h
`
`<1} snquzucz CHARACTERISTICS:
`(5) LENGTH: 10 base pairs
`(B) TYPE: nucleic acid
`(C) STRANDEDNESS: single
`(D) TOPOLDGY:
`linear
`
`(11) HOLECULE TYPE: DNA (genomic)
`
`(iii) HYPOTHETIGAL: N0
`
`(iv) ANTI-SENSE: ND
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID H0119:
`CTATTCTTAG
`
`(2)
`
`INFURMATIDN FOR SEQ ID N0:20:
`
`(i) SEQUENCE CHARACTERISTICS:
`(A) LENGTH:
`lfi base pairs
`(B) TYPE: nucleic acid
`(C) STRANDEDNESS: single
`(D) TOPOLDGY:
`linear
`
`(ii) MOLECULE TYPE: DNA (genomic)
`
`(iii) HYPOTHETICAL: N0
`
`(iv) ANTI-SENSE; NO
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID NU:20:
`
`CTAAGAATAG GGCC
`
`(2)
`
`INFORMATION FOR SEQ ID NO:21:
`
`(1) SEQUENCE CH&RACTERISTICS:
`(A) LENGTH:
`lb base pairs
`(B) TYPE: nucleic acid
`(C) STRANDEDNESS: single
`(D) TOPOLOGY:
`linaar
`
`(ii) MOLECULE TYPE: DNA (genomic)
`
`(iii) HYPOTHETICAL: NU
`
`(iv) ANTI-SENSE: NO
`
`
`
`
`
`Page 11 of 23
`Page11 of23
`
`
`
`30
`
`10
`
`10
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID N0:16:
`
`CTAAGAATAG GCCCCCCTTG GGAAGTAGCT
`
`(2)
`
`INFORMATION FOR SEQ ID NO:lT:
`
`(1) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 10 base pairs
`(B) TYPE: nucleic acid
`(C) STRANDEDNESS: single
`{D) TCPCLOCY:
`linear
`
`(ii) MOLECULE TYPE: DNA {genomic}
`
`(111) HYPCTHETICALZ N0
`
`(iv) ANTI-SENSE: NU
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID ND:1?:
`AG CTACTT C C
`
`(2)
`
`INFORMATION FOR SEQ ID NO:l8:
`
`(i) SEQUENCE CHARACTERISTICS!
`(A) LENGTH: 10 base pairs
`(B) TYPE: nucleic acid
`(C) STRANDEDNES5: single
`(D) TOPOLDGY:
`linear
`
`(ii) MOLECULE TYPE: DNA (genomic)
`
`(iii) HYPOTHETICAL: NO
`
`(iv) ANTI-SENSE: NO
`
`(ix) FEATURE:
`(A) NAME/KEY: misc_feature
`(3) LOCATION:
`(5"5)
`/note— "Coding sequence located at
`(D) OTHER INFORMATION:
`indicated position“
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID NC:1B:
`
`CAAGGGGGCC
`
`(2)
`
`INFORMATION FCR.SEQ ID N0:19:
`
`71;
`
`fig
`
`
`
`Page 12 of 23
`Page12of23
`
`
`
`(xi) SEQUENCE DESCRIPTION: SEQ ID NO:21:
`
`CTTGGGAAGT AGCT
`
`(2)
`
`INFORMATION FOR SEQ ID ND:22:
`
`(1) SEQUENCE CHARACTERISTICS:
`(A) LENGTH: 11 base pairs
`(3) TYPE: nucleic acid
`cc) STRANDEDNESS: single
`(D) TOPOLDGYI
`linear
`
`(ii) MOLECULE TYPE: DNA (genomic)
`
`(iii) HYPOTHETICAL: N0
`
`(iv) ANTI-SENSE: NO
`
`(xi) ssquamca DESCRIPTION: szq ID N0:22:
`AGCTACTTCC C
`
`1h
`
`11
`
`——H
`
`
`
`Page 13 of 23
`Page 13 of 23
`
`
`
`In the claims:
`X
`Please amend claims 24, 25, 26, 27, and 28 as follows:
`
`
`claim-gflitonce amended) A method for preparing a library
`[comprising] hazing a plurality of bifunctional molecules
`[according to claim 11] comprising the steps of:
`a} providing a linker molecule E having termini A’ and C‘
`according to the formula A‘-B—C' that is adapted for
`
`reaction with [a chemical] an_aminn_asid precursor unit X‘
`
`b)
`
`at [termini] terminus A‘ and with a nucleotide precursor 2'
`at [termini] terminus C‘;
`conducting syntheses by adding [chemical] ;he_am1nQ_a;id
`precursor unit X‘ o£_said_step_a to [termini] terminus 3' of
`said linker and adding [precursor unit identifier
`oliqonucle-otide]mm to
`
`[termini] terminus C"of said linker. to form a composition
`containing bifunctional molecules having the structure Xn-B-
`Znshere_n_hJL3msiIi9n_identiIier_£cr_x_and,ziandihesithe
`+.
`
`. E
`
`:
`
`repeating step {b} on one or more aliquots of the
`composition to produce aliquots that contain a product
`containing a bifunctional molecule;
`combining the aliquots produced in step (c) to form an
`
`6)
`
`admixture of hifunctional molecules,
`library.
`
`thereby forming said
`
`claim }£éZYonce amended) The method of claimfzf wherein said
`
`steps (c) and (d) are repeated on the admixture of step {d} to
`add an additional [chemical] amino_acid unit x and corresponding
`identifier oligonucleotide Z to the bifunctional molecules in the
`
`-.1‘...
`
`
`
`Page 14 of 23
`Page14of23
`
`
`
`admixture.
`
`fi\ rZ///
`
`(once amended) The method of claim In wherein said
`claim I‘.
`repetition of steps (c) and (d) are repeated on the admixture
`
`A IeHresented_hy_the_£9rmn1a_uQll on said hifunctional molecules
`
`[from 1 to 6 times] £zom_l_Lo_5fi_;1mee,
`
`thereby forming a polymer
`
`-;_J
`”
`
`such that a is an_inreger_Hhich_renIesents_the_length_o£_:he
`polxmer_A_Hith_a_xalne from [3 to 10] £_to_§Q-
`
`claim 1;? (once amended) An alternating parallel method for
`synthesizing a bifunctional molecule of a type represented by the
`formula 1-n-c, wherein:
`
`fig)
`
`I is a [chemical] oolypeofiide polymer including a sequence of
`
`[polymer] amino_acid subunits having a distal end and a
`distal [polymer] aminnrecid subunit,
`the distal end being
`
`the distal [polymer]
`distal from the linker molecule 3,
`amino_eoio subunit being the [polymer] emino_eoid subunit of
`the [chemical] polypeptide polymer at the distal end of the
`sequence of polymer units;
`
`3 is a linker molecule operatively linked to A and to o, and
`c is a genetic tag employing a sequence of unit identifier
`
`oligonucleotides for encoding and identifying the [chemical]
`polypeptide polymer 1,
`the sequence of unit identifier
`oligonucleotides having a distal end and a distal unit
`
`the distal end being distal from
`identifier oligonuoleotide,
`linker molecule B,
`the distal unit identifier
`
`oligonucleotide being the unit identifier oligonucleotide at
`the distal end of the sequence of unit identifier
`oligonucleotides;
`the method comprising the steps of:
`Step A: providing a first precursor bifunctional molecule
`
`having the formula L‘-B-G’, wherein:
`
`A‘
`
`is a first precursor [chemical] eolyoeotioe polymer
`
`v
`
`
`
`Page 15 of 23
`Page 15 of 23
`
`
`
`[polymer] amino_acid Bubunitfi Of
`having the sequence of
`[chemical] polypeptide polymer A without the distal
`[polymer] nminn_acid subunit, and
`c'
`is a first precursor genetic tag having the sequence
`of unit identifier oligonucleotidee of genetic tag o
`without the distal unit identifier oligonucleotide;
`then
`stop B: elongating the sequence of [polymer] amino_agid
`subunits of the first precursor [chemical] polypeptide
`polymer 3' by addition of the distal [polymer] amino
`acid subunit for producing [chemical] polypeptide
`polymer 1; and
`step C: elongating the sequence of unit identifier
`oligonucleotides of the first precursor genetic tag C’
`by addition of the distal unit identifier
`oligonucleotide for producing the genetic tag C;
`whereby completion of both said step B and Step C results in the
`synthesis of the bifunctional molecule A-B-c.
`5
`claim ‘f.(once amended} an alternating parallel method for
`synthesizing a bifunctional molecule of a type represented by the
`formula 3-3-c as described in claim%if wherein said Step A
`comprises the following substeps:
`substep A’: providing a second precursor bifunctional
`molecule having the formula n'—s-c", wherein:
`3' is a second precursor [chemical] pglxpetide polymer
`having the sequence of
`[polymer] aminn_ncid subunits of
`[chemical] polyngtide polymer 1 without both the distal
`[polymer] aming_acin subunit and [a polymer] gn_nm1ng
`acid subunit adjacent to the distal [polymer] amino
`acid subunit, and
`C” is a second precursor genetic tag having the
`sequence of unit identifier oligonucleotides of
`-16..
`\. .1‘\
`lg/C>
`
`
`
`Page 16 of 23
`Page 16 of 23
`
`
`
`genetic tag 0 without both the distal unit
`identifier oligonucleotide and a unit identifier
`
`oligonucleotide adjacent to the distal unit
`identifier oliqonucleotide; than
`
`‘
`
`\~_J
`
`suhstep B‘: elongating the sequence of [polymer] am1nQ_agifl
`subunits of the second precursor [chemical] polyyetide
`polymer 1' by [a] an addition of the [polymer] §m1ng_gg1fi
`
`subunit adjacent the distal [polymer] nmin9_1r:..i.n subunit for
`
`producing first precursor [chemical] polypeptide polymer 3';
`Substep C‘: elongating the sequence of unit identifier
`
`oligonucleotides cf the second precursor genetic tag 0' by
`addition of the unit identifier cligonucleotide adjacent to
`the distal unit identifier oligonucleotide for producing the
`first precursor genetic tag C‘;
`
`whereby completion of both said step 13' and step C' results in
`the synthesis of the first precursor hifunctional molecule h'-B-
`c' of said Step A.
`
`
`
`Page 17 of 23
`Page 17 of 23
`
`
`
`REMARKS
`
`Applicant wishes to express appreciation to Examiner for her
`careful review of the specification and claims and respectfully
`
`requests that the Examiner enter the above indicated amendments
`in order to ready this application for issue.
`
`The above indicated claim amendments are made to narrow the
`
`scope of the claims commensurate with that of the specification
`and clarify the subject matter of the invention.
`The amendments
`
`add no new subject matter and are supported by the specification.
`
`5eqsnce_Lieting:
`
`The instant diviional application was filed without the
`
`sequence listing from the parent.
`
`To bring the application into
`
`the CRF disk
`compliance with 3? CFR 1.821(a){1] and {a}[2),
`containing the sequence listing from the parent application has
`been incorporated into the instant application by amendment.
`
`Furthermore, a print out of the sequence listing from parent CRF
`disk has been added to the specification of the instant
`application by amendment.
`The incorporated CRF disk and paper
`print out are the same and contain no new matter.
`
`Rejections:
`
`The issues in this case can be divided into two groups,
`
`viz.:
`
`1. Claims 24-23 stand rejected under 35 U.S.C. 5112, first
`paragraph on the grounds that the specification does not
`support the recited claims; and
`
`2. Claim 24 stands rejected under 35 U.S.C. 5112, second
`paragraph for being indefinite.
`
`-13..
`
`
`
`Page 18 of 23
`Page 18 of 23
`
`
`
`In claim 24, Applicant has amended the claim by replacing
`the term ‘chemical' with the term ‘amino acid‘ and replacing the
`term ‘termini’ with the term ‘terminus' to narrow the scope and
`clarify the invention. Furthermore, Applicant has add the phrase
`I
`i
`I
`K
`.3
`if.
`:
`:
`1
`z
`3
`I
`I]
`J
`E
`
` LlmmLB to provide a
`definition for the variable Hf. Addition of the amendments are
`supported by the specification and add no new subject matter.
`
`In claim 25, Applicant has amended the claim by replacing
`the term ‘chemica1' with the term ‘amino acid‘ to narrow the
`Addition of the amendment is supported
`scope of the invention.
`by the specification and adds no new subject matter.
`
`In claim 26, Applicant has amended the claim by replacing
`the range from 1 to 6 times to l_to_££_iimes and adding the
`phrases: L and an_intesaJ':..£hich
` and extending
`the value of a from [3 to 10] 2 to 59.
`Addition of the
`amendment provides antecedent basis for ‘a' and is supported by
`the specification and adds no new subject matter.
`
`In claims 27-28 Applicant has amended the claims by
`replacing the term ‘chemica1‘ polymer with the term ‘polypeptide'
`polymer and the term “po1ymer‘ subunit(s) with the term ‘amino
`acid‘ subunitfs) to narrow the scope of the invention. Addition
`of the amendments are supported by the specification and add no
`new subject matter.
`
`..1g._
`
`
`
`Page 19 of 23
`Page 19 of 23
`
`
`
`.
`
`.
`
`_
`
`E.
`
`1:
`
`Claims 24-28 are rejected under 35 U.S.C. 5112, for not
`enabling the specification to be commensurate with the scope of
`the claims. Applicant's amendments to these claims should
`overcome these rejections.
`
`Claims 24-26 are directed to a method for synthesizing a
`libarary comprising a plurality of bifunctional molecules and
`claims 27-23 are directed to an alternating parallel method for
`synthesizing a bifunctional molecule.
`The Examiner takes the
`position that the disclosure of the specification provides a
`single working example using 5' BHC3 as a linker molecule
`operatively linked to a polypeptide and a polynucleotide which is
`too narrow for the claims. Furthermore,
`the Examiner points out
`that the specification provides no direction as to which types of
`linkers would be appropriate for use with which types of chemical
`moieties as claimed in the claims.
`
`Applicant agrees with the examiner that the claims are broad
`in scope.
`The specification provides a working example of a
`linker molecule operatively linked to a ‘polypeptide' and a
`polynucleotide but the claims recite a broader case wherein a
`linker molecule is adapted for a ‘chemical‘ precursor and a
`nucleotide precursor.
`To overcome this rejection, applicant has
`amended the claims 24-26 by replacing the term “chemical
`precursor unit‘ with the term ‘amino acid precursor unit‘ and
`amended claims 27-28 by replacing the terms ‘chemical polymer‘
`and ‘polymer subunit' with the terms ‘polypeptide polymer‘ and
`‘amino acid subunit‘, respectively.
`
`The above amendments narrow the claims to include only those
`bifunctional molecules which comprise of a polypeptide polymer
`.-.20-
`
`
`
`Page 20 of 23
`Page 20 of 23
`
`
`
`The
`and nucleotide polymer linked by a linker molecule.
`amendments narrow the claims by replacing the use of any chemical
`
`to those which are sns§i£i£_£Qr
`(x;)
`unit or chemical polymer
`amino acid units and polypeptide polymers.
`By narrowing the
`claims in this way, the invention is directed to bifunctional
`molecules or libraries therof, which comprise of amino acid units
`
`that make up a polypeptide polymer linked by a linker molecule
`which links a nucleotide polymer.
`
`By narrowing the claims to the use of amino acid units and
`polypeptide polymers, applicant does not need to provide further
`
`direction on the use of the myriad of possible chemical linkers
`which Examiner feels would be necessary if any chemical moiety
`
`were claimed. Applicant claims a specific linker molecule B
`
`having termini A’ and C‘ according to the formula A'eB-C‘ that is
`
`adapted for reaction with an amino acid precursor unit X‘ at
`terminus A‘ and with a nucleotide precursor 2' at terminus C‘.
`
`The working example in the specification uses 5'BMC3 as a linker
`molecule. This example is representative of all linkers which are
`adapted for amino acid and nucleotide precursors. Therefore,
`the
`
`identification of specific linkers appropriate for use with
`
`different types of chemical moieties is a moot point.
`
`Accordingly, Applicant requests that the 35 U.S.C. 5112
`enablement rejection be overcome by the above indicated
`amendments for the above stated reasons.
`
`.
`
`I:
`i
`1
`.
`J
`E
`I.
`Claim 24 is rejected under 35 U.S.C. 5112, second paragraph
`
`as being indefinite for failing to_particular1y point out and
`distinctly claim the subject matter which the applicant regards
`
`as invention. Applicant's amendments to these claims should
`
`overcome these rejections.
`
`
`
`Page 21 of 23
`Page 21 of 23
`
`
`
`Applicant has clarified claim 24 by replacing the word
`‘termini' with the word ‘terminus’
`in the respective places to
`indicate that there exists one terminus A‘ and one terminus C‘,
`which is in accordance with the specification.
`The replacement
`reflects a clerical error and adds no new matter.
`
`Examiner's position that it is not clear how a nucleotide
`can serve as a specific tag for a specific
`attached to C‘
`attached chemical moiety is moot point since the invention is
`directed to a method for synthesizing a bifunctional molecule and
`a library comprising a plurality of hifunctional molecules.
`since the invention is a method for making bifunctional molecules
`and not a method for identifying which chemical moiety is
`attached to which nucleotide, applicant traverses this rejection
`and respectfully requests that this rejection be withdrawn.
`
`claim 26 is rejected under 35 U.S.C. 5112 for failing to
`provide an antecedent basis for "a" in the claim. Applicant's
`amendments to these claims should overcome these rejections.
`
`Applicant has amended the claim by including the phrase
` .L. which provides an antecedent
`basis for the variable "a" and is defined by the added phrase an
`
`from 2_tn_5Q after repeating steps (c) and (d) £:gm_1_;g_5fi
`times. Applicant has retained the variable “a” to denote that
`the length of the polymer can be from 2 to 50 units.
`The
`amendments add no new matter and are supported by the
`specification on page 8,
`lines 11-19 and page 11, lines 4-6.
`
`_ 22 -
`
`
`
`Page 22 of 23
`Page 22 of 23
`
`
`
`Enmmflrfli
`
`applicant believes that claims 24-28, as amended, have the
`requisite definiteneas and particularity required under 35 Use
`5112, first and second paragraph.
`
`Applicant requests that the Examiner examine Claims 24-28 in
`View of the amendments and remarks indicated above.
`The Examiner
`
`is requested to withdraw the rejection of claims 24-28 and to
`provide the Applicant with a Notice of Allowance with respect to
`the amended claims.
`
`Respectfully submitted,
`
`UK)/QX/92-_‘.
`Donald G. Lewis
`Reg. No. 28,636
`The Scripps Research Institute
`10666 N. Torrey Pines Road TPC-B
`San Diego, CA 92037
`June 6, 1997
`(619) 784-2937
`
`_23_
`
`
`
`Page 23 of 23
`Page 23 of 23
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