Applicants: Stavrianopoulos et al.
`
`Serial No.
`
`08/486,070
`
`Filed:
`
`June 7, 1995
`
`Title: COMPOSITION EMPLOYING CHEMIC-
`ALLY LABELED OLIGONUCLEOTIDE OR POLY-
`NUCLEOTIDE, AND APPARATUS AND ARRAYS )
`CONTAINING A COLLECTION 0R SET OF SAME)
` .?__j.i
`)
`
`._‘4‘¢‘—\,_._—_—.—
`
`New Group Art Unit: 1634
`
`Examiner: Ardin H. Marschel, Ph.D.
`
`527 Madison Avenue, 9th Floor
`New York, New York 10022
`July 30, 1999
`
`Honorable Commissioner of Patents and Trademarks
`The United States Patent and Trademark Office
`Washington, D. C. 20231
`
`COMMUNICATION
`
`[FOLLOWING APPLICANTS‘ MAY 18, 1998
`THIRD SUPPLEMENTAL AMENDMENT)
`
`Dear Sir:
`
`This is a Communication following Applicants’ May 18, 1999 Third
`
`_.
`
`l
`
`\D
`i
`
`("3
`
`<41
`l\u
`Q
`E
`(3
`M9%
`
`‘ Supplemental Amendment that was filed in the above-identified application. No
`extension or additional fee is believed due in connection with this Communication,
`
`a Request For An Extension Of Time (3 Months) and authorization for the fee
`
`having been previously paid with Applicants’ July 21, 1998 Amendment.
`
`Accordingly, this Communication is being timely filed.
`
`
`
`EXPRESS MAIL CERTIFICATE
`
`"Express Mail" Label No. EL369155362US
`Deposit Date
`July 30, 1999
`I hereby certify that this paper and the attachments
`herein are being deposited with the United States Postal
`Service "Express Mail Post Office to Addresses" service
`under 37 CFR 1.10 on the date indicated above and is
`addressed to the Commissioner of Patents and
`T
`marks,
`hington DC 20231.
`
`
`
`
`
`
`
`
`
`
`
`
`
`Ronald C. Fedus
`Reg. No. 32,567
`
`U'Ui:r 30 3 21
`Date
`
`Page 1 of 12
`Page 1 of 12
`
`E"""""°3’
`
`BD EXHIBIT 1030
`BD EXHIBIT 1030
`
`

`
`Stavrianopoulos et al.
`Serial No.: 08/486,070
`
`Filed: June 7, 1995
`
`REMARKS
`
`Claims 183-376 were previously presented in Applicants‘ May 18, 1999
`
`Third Supplemental Amendment. These claims continue to be presented for further
`
`examination in this application, no changes having been requested in this
`
`Communication.
`
`The purpose of this Communication is to present evidence bearing on the ‘
`
`commercial success of products manufactured and distributed by Enzo Diagnostics,
`
`|nc., the instant assignee of this application. Marketed under Enzo's tradenames,
`
`Enzo Bioarraym High Yield“ RNA Transcript Labeling Kit and BioArrayTM Terminal
`
`Labeling Kit, these products are being distributed by a major array or gene chip
`
`company, Affymetrix, Inc. of Santa Clara, California, for use in connection with
`
`Affymetrix GeneChip® arrays. Attached to this Communication as Exhibit A are
`product specification sheets for thetwo foregoing products. Further- attached as
`Exhibit B are product literature sheets for Enzo's aforementioned Bioarray-TM High
`
`-1-Yield” RNA Transcript Labeling Kit distributed by Affymetrix, Inc. in connection
`
`with its gene chips. A May 27, 1998 news release announcing the distributorship
`
`agreement between Enzo and Affymetrix in which the former will be the sole
`
`supplier of nucleic acid labeling and detection products for Affymetrix‘ GeneChip®
`
`arrays worldwide is also attached as Exhibit C.
`
`The instant Assignee is also the exclusive supplier of reagent products for
`
`labeling and detecting gene sequences in connection with Flow-thru Chip“ probe
`
`arrays manufactured and sold by Gene-Logic, Inc. of Gaithersburg, Maryland. A
`
`copy of a March 23, 1999 news release announcing Enzo's arrangement with
`
`Gene-Logic is attached as Exhibit D.
`
`Consideration to the information and'documents being submitted herewith in
`
`the form of Exhibits A-D is respectfully requested.
`
`*4!-***-ll-*
`
`Enz-7(P)(C3l
`
`Page 2 of 12
`Page 2 of 12
`
`

`
`\PEv
`
`9.
`a
`'3:
`Stavrianopoulos et al.
`‘"1 3‘_”~‘99 V
`Serial No.: 08/486,070
`'
`.5?
`Filed: June 7, 1995
`Page 3 [Communication (Following Applicants‘ May 18, 1999 Third
`Supplemental Amendment(- July 30, 1999)]
`
`
`
`- O
`
`.,
`
`SUMMARY AND CONCLUSIONS’
`
`Claims 183-376 continue to be presented for further examination.
`
`No other fee is believed due in connection with this Communication, a three
`
`month extension fee having been previously authorized in connection with '
`
`Applicants‘ July 21, 1998 Amendment Under 37 C.F.R. §1.115.
`
`In the event that
`
`any other fee or fees are due, however, either in connection with this
`
`Communication or with any of Appli-cants' previous filings, The Patent and
`
`Trademark Office is hereby authorized to charge the amount of any other such feels)
`
`to Deposit Account No. 05-1 135, or to credit any overpayment thereto.
`
`If it would be helpful to expediting the prosecution of this application, the
`
`undersigned may be contacted by telephone at 212-583-0100 during the daytime
`business hours.
`
`Early and favorable action on this application is respectfully sought.
`
`Respectfully s bmitted
`
`
`
`Ronald C. Fedus
`Registration No. 32,567
`Attorney for Applicants
`
`ENZO DIAGNOSTICS. INC.
`clo Enzo Biochem, Inc.
`527 Madison Avenue (9th Floor)
`New York, New York, 10022
`Telephone: (212) 583-0100
`Facsimile: (212)583-0150
`
`Enz—7(P)(C3)
`
`Page 3 of 12
`Page 3 of 12
`
`

`
`§Enza ‘
`
`B ioArray“‘
`High Yield”
`RNA Transcript Labeling Ki
`
`10 labeling reactions
`
`Distributed by Affymetrix, Inc.
`
`Part No. 900182
`
`For Research Use Only
`
`
`INTRODUCTION
`
`The ENZO BIoArray"‘ HIghYIeId'“ RNA Transcript Labeling Kit
`has been developed for the production of
`large amounts of
`hybridizable biotin-labeled RNA targets by in wire transcription from
`bacteriophage 17 RNA polymerase promoters.
`Using 17 RNA
`polymerase and biotin-labeled nucleotides, largearnounts of single
`stranded nonradioactive RNA molecules can be produced in vitro.
`Because of the nature of transcription reactions, many RNA copies of
`the template DNA are produced during a short incubation. Because
`FlNA—DNA hybrids
`have
`a
`higher melting
`temperature than
`corresponding DNA-DNA hybrids, single-stranded RNA targts offer
`higher target avidity and greater sensitivity than DNA probes. RNA
`targets offer selectivity unavailable with DNA targets—being single
`stranded,
`they are strand-specific and hybridize more effectivety to
`probes because the target population does not self-hybridze.
`RNA transcripts
`that
`are
`labeled
`with
`biotin-modified
`ribonucleotides are used effectively in microchip array assays. The
`biotin—labeled RNA targets that are hybridized to arrays of DNA probes
`can be detected by a reporter molecule linked to streplavidin, avidin or
`anti-biotin antibody. Such a complex can be detected drectly, e.g., by
`excitation of a fluorophore conjugated to streptavidin, or indirectly, e.g.,
`using an enzyme conjugate that can produce an insoluble colored
`precipitate.
`The ENZO BIoArray'" HlghYleId“ RNA Transcript Labeling Kit
`has been formulated and optimized for use with Afrymetrix GeneChip°
`assays. The kit contains all of the reagents required to perform 10
`reactions with approximately 1 pg of transcribable cDNA template such
`as the product of the Aftymetrix Expression Analysis Technical Manual
`sample preparation protocols, or a control such as plasmid template
`DNA (0.4 pmol).
`
`REAGENTS PROVIDED
`
`10X HY Reaction Butler, 40 pl
`
`10X DTT, 40 pl
`
`10X Biotin Labeled Rlbonucleotldes, 40 pl
`ATP, GTP, CTP, UTP with Bio-UTP and BioCTP
`
`20X 17 RNA Polymerase, 20 pl
`in Storage Buffer
`
`10X RNase Inhibitor Mix, 40 pl
`in Storage Buffer with enhancer
`
`EQUIPMENT AND REAGENTS REQUIRED BUT NO
`PROVIDED
`
`Preparation of RNA Transcripts
`o Water bath or heat block set to 37°C
`- DEPC-treated, sterile, deionized water
`
`STORAGE
`
`Store all reagents at -290, in a freezer that is not self-defrosting.
`
`RNA LABELING
`
`When preparing RNA for use with Arfymetrix Genechlp
`Expression Arrays, please refer to the Affymefrix Expression Analysis
`Technical Manua, Chapter 3, “Synthesis of Biotin-Labeled cRNA
`(lVT)" and Chapter 4, “Control cRNA Preparation".
`
`A. Template Preparation
`
`For control plasmid templates, linearize the plasmid DNA using
`appropriate restriction enzyme digestion or the template.
`
`a Linearized template DNA should be purified before adding to
`the reaction.
`
`leave a 3’ overhang should be
`a Restiction enzymes that
`avoided because T7 RNA polymerase may transcribe these ‘in
`a promoter independent manner.
`
`0 Use only RNase-tree water, buffers and pipette tips.
`
`B. RNA Transcript Labeling Reaction
`1. Add reaction components to RNase-free microtuge tubes.
`2. Make additions in the order indicated in the following table.
`
`NOTE: Keep reactions at room temperature while additions are
`made to avoid precipitation of DTT.
`
`Re
`nt
`Volume
`
`Tgmpme DNA
`
`Distilled or deionized water
`
`10X HY Reaction Butter
`10X Biotin Labeled Hibonucleotides
`10X DTT
`10X RNase Inhibitor Mix
`20X ‘l7 RNA Polymerase
`Total Volume
`
`variable to give I pg 01 cDNA or
`0.4 pmol (about 1 pg of a 3.8 kb
`plasmid}
`variable (to give a final reaction
`volume of 40 pl)
`4 ”|
`4 pl
`4
`I
`I!
`4 pl
`2
`I
`H
`40
`
`3. Careiully mix the reagents and collect the mixture in the bottom
`of the tube by brief (5 second) microcentrifugation.
`
`4.
`
`Incubate for
`Immediately place the tube in a 37°C water bath.
`4 to 5 hours, gently mixing the contents of the tube every 30-45
`minutes during the incubation. Longer reaction may increase
`yield, but the possibility of degradation by RNase increases‘.
`‘
`
`5. Approximately 50-100 pg of RNA product are usually produced
`in each standard reaction (40 pl reaction containing 1 pg or
`template DNA). Larger amounts or products can be prodrced
`by scaling up all components and volumes.
`in most scale-up
`syntheses, the amount or DNA template can be reduced to 0.5-
`0.8 pg per 40 pl of reaction mixture.
`
`6. Store at -20°C if not purifying RNA immediably.
`
` ©1998
`Aflymetrlx, Inc. 3380 Centml Expressway, Santa Clara, CA 95051
`Enzo Diagnostics, Inc. 60 Execufive Boulevard, Farmingdale, NY 11735
`
`Page 4 of 12
`Pae 4 of 12
`
`

`
` .BioArray"‘ HighYieldm RNA Transcripthzbeling”
`
`PURIFICATION OF LABELED RNA TRANSCRIPTS
`
`recommend RNeasy spin
`We
`purification of labeled RNA.
`
`columns
`
`from QIAGEN for
`
`For Research Use only
`
`Afiymarix probe arrays.
`
`is manutactured by ENZO DIAGNOSTICS, INC. for
`This product
`distribution by Afiymetrix, Inc. for research purposes only by the end~user
`and "s not intended fordiagnostic or therapeutic use. Purchase does not
`include a icense or the right to utilize this product except lor research
`purposes. Purchase does not include the right to diflribute or sell this
`product commercially. As distributed by Affymetrix, Inc., this product may
`be used only in conjunction with and is pennitted ior use only with
`
`For Technical Assistance call ENZO:
`Toll free from the U.S. and Canada: 1-800-221-7705
`All others: 516-694-7070
`Fax: 516-694-7501
`
`Aflymetrix, Inc.
`3380 Central Expresswa
`Santa Clara, CA 95051
`
`Enzo is a registered trademark oi Enzo Bicchem, Inc. and BioArray is a trademark of Enzo
`Biochom, Inc.
`Atfymetrix and Genechip are registered trademarks oi Atty matrix, Inc.
`
`This product or the use 01 thls product is covered by one or more claims 01 Enza
`patents Includlng, but not llmlted to. the Iolloulngz u.s. Patent Nos. 5,328,824
`5,449,767; 5A16,928; 4,111,955 and 4,994,373; EP 0 063 879 B1; EPO:-In 198 B1
`DK 111 an 8; Canadian Patent Nos. 1.219524 and 1,309,672: Japanese Patent Nos.
`2,131,226: 1A16,584 and other patents pending.
`
`900 182-00-98 12
`7- 1236
`
`REV. 1
`
`___
`Affymetrlx, Inc. 3380 Central Expressway, Santa Clara, CA 95051
`© 1993
`Enza Diagnostics, Inc.
`60 Executive Boulevard, Farmingdale, NY 11735
`
`Page 5 of 12
`Page 5 of 12
`
`

`
`§Enza .
`
`BioArray"‘
`Terminal Labeling Kit
`with Biotin-ddUTP
`
`for DNA Probe Array Assays
`
`25 labeling reactions
`
`Distributed by Affymetrix, Inc.
`
`Part No. 900181 Rev. 1
`
`For Research Use Only
`
`
`INTRODUCTION
`
`The ENZO BioArray"‘ Terminal Labeling Kit (with Biotin-
`ddUTP) for Affymetrix GeneChip® DNA Probe Arrays has been
`developed by Enzo specifically for use with the array. The method of
`labeling uses biotin-ddUTP and terminal deoxynucleotid transterase
`to catalyze the addition of a single biotin ddUMP to the 3'-OH terminus
`of the amplified and fragmented target DNA. A standard reaction will
`label up to 100 picomoles (1 pg of a 30-nucleotide sequence). When
`DNA fragments are labeled at the 3’-OH terminus, the sequence bias
`that occurs with either nick translation or random priming is eliminated.
`
`This labeling kit has been formulated and optimized for use with
`Affymetrix GeneChip® assays.
`
`REAGENTS PROVIDED
`The ENZO Bio/trrayi“ Terminal Labeling Kit (with Biotin-
`ddUTP)
`for Affymetrix DNA Probe Arrays contains
`sufficient
`reagents for 25 labeling reactions of 100 picomoles of fragmented
`DNA, corresponding to 25 x tpg of a 30-nucleotide sequence.
`
`Biotin-ddUTP (1oox), 25 pl
`
`5X Reaction Buffer, 500 pl
`Potassium cacodylate buffer, pH 7, containing B-mercaptoethanol
`and stabilizer
`
`10X cocr, Solution, 250 pl
`
`Terminal Deoxynucleotlde Transferase (50X), 50 ul
`in storage buffer
`
`WARNING: The 5X Reaction Buffer and Terminal Deoxynucleotlde Transferase contain
`potassium cacodylafe which contains arsenic.
`It is toxic. Use gloves dur’ng the handling of
`mass reagents. Dispose of these reagents and the individual labeling reaction waste materials
`according to local regulations.
`
`Enzo is a registered tradenark ol Enzo Biochem, Inc. and BioArray is a trademark of Enzo
`Biochern, Inc.
`Attyrnetrix and Genechip are registered trademarks cl Affymetrix, Inc.
`
`This product or the use orthis product is covered by one or more claims of Enzo
`patents Including. but notllrnlted to, the following: U.S. Patent Nos. 5,328,&4
`5,449,167; 5,476,928; 4,711,955 and 4,994,373; EP 0 063 879 81: EP 0 329198 B1:
`EP 0122 614 B1; DK 171 822 8; Canadian Patentllos. 1,219,824; 1,254,525 and
`1,309,672; Japanese Patent Nos. 2,131,226; 1,416,584 and 2,595,201 and other patents
`pending.
`
`REAGENTS AND MATERIALS REQUIRED
`
`Preparation and Analysis of Labeled DNA Fragments
`o 37°C Water Bath
`
`- Agarose gel (e.g., 4%) - optional
`- UV Transilluminator- optional
`
`Termination of Labeling Reaction
`o 0.2 M EDTA, pH 8
`
`STORAGE
`
`Upon receipt, store all reagents at -20 °C,
`self defrosting.
`
`in a freezer that is not
`
`PROCEDURE FOR TARGET LABELING
`
`Refer to Affymetrix package insert
`fragmentation procedures.
`
`for
`
`target amplification and
`
`the indicated order) to a
`(in
`reagents
`the following
`1. Add
`microcentrifuge tube, keeping the tube at room temperature while
`additions are made:
`
`
`Volume
`Reagm
`20 pi
`5X Reaction Butler
` _a__
`
`10X CoCi2 10 in_:
`
`variable (as specified in Affymetrix
`Amplified and fragmented target
`target amplification and fragmentation
`pad<age insert)
`
`Biotin-ddUTP 1 pl
`Terminal Deoxynucleotide
`2 pi
`Transferase __?m:
`Distriied or deionized water
`variable (to give a final reaction
`volume
`of 100 pl)
`
`Total Volume 100 pl
`
`2. Carefully mix the reagents in the tube and collect the mixture in the
`bottom of
`the microcentriiuge
`tube
`by
`brief
`(5
`seconds)
`microcentrifugation.
`
`3.
`
`4.
`
`incubate the tube for 15 minutes in a37 °C water bath. The
`reaction may be allowed to proceed for up to 1 hour.
`
`If desired, transfer the tube to ice water (2-4’C), remove 2 pi and
`analyze on an agarose or acrylamide gel.
`
`5. Stop the reaction by adding 5 pl of 0.2 M EDTA.
`
`6. Store the labeled DNA fragments at -20°C. Do not freeze and
`thaw repeatedly.
`
`For Research Use Only
`inc. for
`is manutactured by Enzo Diagnostics.
`This product
`distribution by Affymetrix, inc. for research purposes only by the end
`user and is not Intended for diagnostic or therapeutic use. Purchase
`does not Include a license or the rlht to utilln this product except for
`research purposes. Purchase does not include the right to distribute
`or sell this product commercially. As distributed by Affymetrix, Inc..
`this product may be used only in conjunction with and is permitted for
`
`use only with Atfyrretrlx probe arrays.
`
`TECHNICAL SUPPORT INFORMATION
`
`Enzo Diagnostics, Inc.
`60 Exemrtive Boubvard
`Farmingdale, NY 11735
`Toll free number. 1-800-221-7705
`Outside US: 516-694-7070
`Fax 516-694-7501
`
`900181-00-9811
`
`Affymetrix, inc.
`3380 Central Exprewrra
`Santa Clara, CA 95051
`
`
`©1998
`Affymetrix, Inc. 3380 Central Expressway, Santa Clara, CA 95051
`Enzo Diagnostics, Inc. 60 Executive Boulevard, Farmingdale, NY 11735
`
`Page 6 of 12
`Page 6 of 12
`
`

`
`GENE EXPRESSION MONIT-ORING
`
`GeneChip®
`Enzo Bioarraym HighYieldm
`RNA Transcript Labeling Kit
`
`
`
`An Essential
`Reagent Kit for
`Preparing Your
`Gene Expression
`Samples
`
`I
`
`Use the Enzo BioArray HighYield
`RNA Transcript Labeling Kit to
`produce biotin-labeled RNA
`targets by in vitro transcription
`from bacteriophage T7 RNA
`polymerase promoters. Using T7
`RNA polymerase and biotin-
`labeled nucleotides, single-
`stranded, non—radioactive RNA
`
`molecules can be produced
`
`m mm
`In vitro transcription reactions
`can now be "performed using a
`single, convenient, high—
`performance kit that was
`developed epeeifiee-‘“Y fer use with
`. Q
`.
`Affymetrix GeneChip expression
`analysis probe arrays.
`_.
`AffY’.“et“" highly recommends
`using this labeling kit in
`Conjunction with the Genechip
`expression analysis probe arrays
`for accurate and high yield results.
`
`@5720
`BioArray“‘
`
`Page 7 of 12
`' Page 7 of 12
`
`
`
`Contact Afljlmetrix today for
`more information on how to
`place your order.
`Us and Canada
`Tel: 8002235281
`Fax: 408.481.9442
`Euro
`9°
`Tel: +44 (0)7000.785.803
`Fax: +44 (0)7000-785-804
`
`www.affymetrix.com
`
`§The BioArray HighYield
`Transcript Kit contains the
`following reagents:
`I 10X Biotin Labeled
`Ribonucleotidag
`- 20x T7 RNA Polymerase
`I 10X HY Reaction Buffer
`I 10X DTT
`I 10X RNase Inhibitor
`
`Complete technical information
`regarding the use of this labeling
`kit is included in the Genechip
`Expression Analysis Technical
`Manual.
`
`A F F Y M E T R I X
`
`/OCH‘:
`GeneChip°
`
`

`
`GeneChip Expression Analysis
`
`g
`
`~_ 1 http://wwwaffymetrix.oom/products/genomics.l1tml
`i1:
`
`
`
`
`
`apuplication areas
`
`
`
`L Expression Analysis
`
`Expression Analysis
`
`
`
`A. GeneChip expression
`arrays simultaneously and
`quantitatively interrogate
`thousands of mRNA
`transcripts (genes or ESTS),
`simplifying large genomic
`studies.
`
`B. Each transcript is
`represented on a probe
`array by multiple probe
`pairs so that you can
`differentiate among closely
`related members of gene
`families.
`
`C. Each probe cell contains
`millions of copies of a specific
`oligonucleotide probe,
`permitting the accurate and
`sensitive detection of
`low-intensity mRNA
`hybridization patterns.
`
`D ifferential expression data can provide a clear understanding of cellular
`pathways and help identify valuable candidates for drug discovery - but only if
`you can trust the data. GeneChip expression analysis enables you to generate
`dependable data on demand.
`
`GeneChip expression probe arrays simplify genomics research by
`quantitatively and simultaneously monitoring the expression of thousands of
`genes. Sensitive and specific, GeneChip probe arrays identify mRNA
`expression level changes of greater than twofold between experiments and are
`able to detect mRNA transcripts from the level of only a few copies per cell to
`more than several hundred thousand copies per cell.
`
`In contrast to spotting methods in which a single clone is used to analyze each
`mRNA, GeneChip expression arrays use approximately 20 pairs of specific
`oligonucleotide probes to interrogate each transcript. This probe pairing
`strategy helps identify and minimize the effects of non—specific hybridization
`and background signal so that you can recognize low-intensity hybridization
`patterns from mRNAs sensitively and accurately. GeneChip expression arrays
`make it possible to specifically detect individual gene transcripts and splice
`variants and even differentiate among closely related members of gene
`families.
`
`lof2
`
`Page 8 of 12
`Page 8 of 12
`
`7/29/99 4:38 PM
`
`

`
`Affyrnetrix Gen_eChip Expression Analysis
`.
`.
`
`, http://wiww.affymetrix.oom/products/genomicshtml
`I}
`
`Each GeneChip expression array contains probes corresponding to a number
`of reference and control genes. Using reference standards, you can normalize
`data from different experiments and compare multiple experiments on a
`quantitative level.
`
`Want more information?
`The following documents are available in Adobe Acrobat (PDF) Format
`(requires Ad9b.e.Asml1a1)
`
`. Product Catalog
`
`. GeneChip Expression Analysis Overview
`
`, Expression Analysis Product Line
`
`. GeneChip Custom Arrays
`
`. GeneChip HuGeneFL Set
`
`. GeneChip Mu6500 Set
`
`, GeneChip Ye6100 Set
`
`. GeneChip Testl
`
`. Enzo BioArrayTM High Yield” RNA Transcript Labeling
`Kit
`
`Relevant Publications
`View a complete bibliographic listing of relevant sgientifig pppligagons.
`
`
`
`Copyright © 1998 Affymetrix, Inc. All rights reserved.
`Legal disclaimer mg ggdemark infgnngjgp,
`
`Last updated July 15, 1999
`
`2 of 2
`
`Page 9 of 12
`Page 9 of 12
`
`7/29/99 4:38 PM
`
`

`
`Enzo
`
`For Immediate Release
`Contact: Barry Weiner
`(212) 583-0100
`
`news
`release
`
`
`
`Enzo Biochem, Inc.
`527 Madison Avenue
`
`New York, NY 10022
`
`ENZO BIOCHEM ANNOUNCES AGREEMENT WITH AFFYMETRIX
`TO BE SOLE SUPPLIER OF LABELING AND DETECTION PRODUCTS
`FOR GENECH|P® ARRAYS
`
`
`FARMINGDALE, NY, May 27, 1998 — Enzo Biochem, Inc. (ASE:ENZ) today
`announced that Enzo Diagnostics, its wholly owned subsidiary has entered into an
`agreement with Affymetrix, Inc. under which Enzo will be the sole supplier of
`specified proprietary nucleic acid labeling and detection products for Affymetrix’
`GeneChip® arrays worldwide.
`
`Under the terms of the agreement, Affymetrix becomes a nonexclusive
`worldwide distributor of Enzo nucleic acid labeling and detection kits to be sold
`together and used with the Affymetrix GeneChip arrays. Enzo manufactures
`customized kits, based on its patented technology, that meet the specifications of
`various Affymetrix GeneChip array products for sale to the research market.
`Affymetrix will package and ship these Enzo products in association with
`GeneChip arrays.
`
`Enzo's products are used to label and detect the nucleic acid sequences
`that are being analyzed with the GeneChip® array.
`
`In addition, Affymetrix will be allowed to use certain Enzo proprietary
`products and technology to optimize existing GeneChip products, and to develop
`new GeneChip products. Certain rights from these developments will be retained
`by each company.
`
`Affymetrix has developed and intends to establish its GeneChip system as
`the platform of choice for analyzing and managing complex genetic information in’
`order to improve the diagnosis, monitoring and treatment of disease. The
`GeneChip system consists of disposable DNA probe arrays containing gene
`sequences on a chip, reagents for use with the probe arrays, a scanner and other
`instruments to process the probe arrays and software to analyze and manage
`genetic information.
`'
`
`Enzo Biochem, a pioneer and leader in the development of nonradioactive
`nucleic acid labeling and detection technologies, holds more than 100 worldwide
`-more-
`
`Page 10 of 12
`Page 10 of 12
`
`

`
`Enzo Biochem, Inc. — Page 2
`
`patents and produces a wide range of proprietary products, that are used in the
`global medical research market and are expected to have broad application in the
`clinical diagnostic market.
`
`"This agreement is further recognition of Enzo’s position as the leading
`developer of nucleic acid labeling and detection systems,” said Elazar Rabbani,
`Ph.D., Chairman and CEO of Enzo Biochem. "We believe that a combination of
`Enzo’s labeling and detection products together with Affymetrix’ GeneChip arrays
`will provide a compelling combination in the rapidly developing area of gathering
`and analyzing genetic information, and we are pleased to be part of this
`development.”
`
`Enzo Biochem is engaged in the research, development and manufacture of
`innovative health care products based on molecular biology and genetic
`engineering techniques, and in providing diagnostic services to the medical
`community.
`
`Except for historical information, the matters discussed in this news release
`may be considered "forward—looking" statements within the meaning of Section
`27A of the Securities Act of 1933, as amended, and Section 21 E of the Securities
`Exchange Act of 1934, as amended. Such statements include declarations
`regarding the intent, belief or current expectations of the Company and its
`management. Prospective investors are cautioned that any such forward—looking
`statements are not guarantees of future performance and involve a number of
`risks and uncertainties that could materially affect actual results.
`
`###
`
`Page 11 of 12
`Page 11 of 12
`
`

`
`I‘
`
`Q" EIIZ
`
`~
`
`.
`
`For Immediate Release
`
`Contact: Barry Weiner
`(212) 583-0100
`
`1.15
`release
`
`
`
`Enzo Biochem, Inc.
`527 Madison Avenue
`
`New York, NY 10022
`
`ENZO DIAGNOSTICS TO SUPPLY REAGENTS
`FOR USE WITH GENE LOGIC FLOW-THRU CHIPSTM
`
`COMPANY ANNOUNCES LIMITED USE AGREEMENT
`
`FARMINGDALE, NY, March 23, 1999 — Enzo Diagnostics, Inc. (ASE:ENZ) announced that it has
`concluded an agreement with Gene Logic, Inc. (NASDO:GLGCl under which Enzo will be the
`exclusive supplier of its patented reagent products for labeling and detecting gene sequences with
`Gene Logic F|ow—thru ChipT"" probe arrays. Under the agreement Gene Logic will be afforded limited
`access to Enzo's patented and proprietary products and technology for internal use in developing
`gene expression data, profiles and genetic databases for research purposes.
`
`"Gene Logic is a genomics company with a significant position in biodata, particularly gene
`expression information,” commented Dr. Dean L. Engelhardt, Enzo's Senior Vice President.
`"Clearly,
`our proprietary nonradioactive nucleic acid labeling, hybridization and detection technology and
`products complement quite well with Gene Logic's efforts in this area. This is an important first
`step in building a working relationship between the two companies. We are presently exploring
`other areas of mutual interest."
`
`"The relationship with Enzo Diagnostics will facilitate the development of Gene Logic's chip-
`based programs," said Larry Tiffany, Gene Logic's Director for Technology and Intellectual Property
`Development.
`
`Enzo Biochem is engaged in the research, development and manufacture of innovative health
`care products based on molecular biology and genetic engineering techniques, and in providing
`diagnostic services to the medical community. The Company currently manufactures over 200
`products utilized in various aspects of molecular biological research.
`It's proprietary ‘non-radioactive
`labeling and detection technologies are being utilized by researchers and companies worldwide.
`
`Gene Logic combines genomic technologies and bioinformatic expertise to provide
`pharmaceutical companies with products designed to reduce the time, cost, and risk associated with
`drug discovery and development. These products include proprietary databases of gene expression
`for drug target discovery and toxicology, a novel screening technology for identifying new drug
`leads, and a pharmacogenomic technology for improving drug effectiveness. Gene Logic's Data
`Logic division, based in Berkeley, CA, develops and markets bioinformatic software for managing and
`integrating genomic data.
`
`Except for historical information, the matters discussed in this news release may be
`considered '’forward—looking’’ statements within the meaning of Section 27A of the Securities Act of
`1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. Such
`statements include declarations regarding the intent, belief or current expectations of the Company
`and its management. Prospective investors are cautioned that any such forward—looking statements I
`are not guarantees of future performance and involve a number of risks and uncertainties that could
`materially affect actual results.
`
`*****-)I-*
`
`Page 12 of 12
`Page 12 of 12