Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 1 of 37 Page ID #:1
`Case 2:13-c-v--07909DOCRNB Document 1 Filed 04/26/13 Page 1 of 37 ”Page ID #:1
`
`
`UNITED STATES DISTRICT COURT
`
`FOR THE SOUTHERN DISTRICT OF NEW YORK CDX DIAGNOSTICS, INC. and
`
`SHARED NIEDICAL
`
`RESOURCES, LLC
`
`Plaintiffs,
`
`V.
`
`) ) ) ) ) ) )
`
`) ) ) g
`
`ECF CASE
`
`) ) )
`
`COMPLAINT
`
`HISTOLOGICS, LLC, POPLAR
`
`I-IEALTHCARE PLLC,
`MATTISON PATHOLOGY LLP
`
`and JOHN DOES 1-30
`
`Defendants.
`
`Plaintiffs CDX DIAGNOSTICS, INC, (“CDX”) and SHARED MEDICAL
`
`RESOURCES, LLC (“SMR”) (CDX and SMR jointly and severally known as
`
`“Plaintiffs”), hereby sue Defendants HISTOLOGICS, LLC (“HISTOLOGICS” ,
`
`POPLAR HEALTHCARE PLLC (“POPLAR”), MATTISON PATHOLOGY LLP
`
`(“MATTISON”) (DEFENDANTS I-IISTOLOGICS, POPLAR and MATTISON jointly
`
`and severally known as “Defendants”) and John Does 1—30 and alleges as follows:
`
`THE PARTIES
`
`1.
`
`Plaintiff CDX is a corporation of the State of Delaware having a principal
`
`place of business at 2 Executive Boulevard, Suffern, New York 10901.
`
`2.
`
`Plaintiff SMR is a limited liability company of the State of Delaware
`
`having a principal place of business at 190 Newport Center Drive, Suite 100, Newport
`
`Histologics, LLC
`
`Exhibit 1019
`
`

`

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`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 2 of 37 Page ID #:2
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`Beach, CA 92660.
`
`3.
`
`Upon information and belief, Defendant Histologics is a limited
`
`liability company of the State of Delaware having a place of business at 20409 Yorba
`
`Linda Boulevard, Suite 119, Yorba Linda, California 92886.
`
`4.
`
`Upon information and belief, Defendant Histologics is engaged in the
`
`business of manufacturing, offering for sale and selling biopsy brushes and conducts
`
`business throughout the United States, the State of New York, and the County of
`
`Rockiand and through the internet at www.kylon.com.
`
`5.
`
`Upon information and belief, Defendant POPLAR is a professional
`
`limited liability company of the State of Tennessee with a place of business at 3495
`
`Hacks Cross Road, Memphis, Tennessee 38125.
`
`6.
`
`Upon information and belief, Defendant POPLAR is engaged in the
`
`business of offering for sale and selling biopsy brushes, providing laboratory testing
`
`services and as a result conducts business throughout the United States, the State of New
`
`York, and the County of Rockland and through the internet at
`
`www.poplarhealthcare.con1.
`
`7.
`
`Upon information and belief, Defendant MATTISON is a limited liability
`
`partnership of the State of Texas with a place of business at 6221 Riverside Drive, Suite
`
`119, Irving, Texas 75039 and is doing business as AVERO DIAGNOSTICS.
`
`8.
`
`Upon information and belief, Defendant MATTISON is a company that
`
`offers pathology services and conducts business throughout the United States, the State of
`
`New York, and the County of Rockland and through the internet at wwwaverodxcom.
`
`9.
`
`Upon information and belief, Defendants JOHN DOES 130 are
`
`

`

`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 3 of 37 Page ID #:3
`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 3 of 37 Page ID #:3
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`individuais, corporations, associations, or other entities that, upon information and belief,
`
`caused, participated in, or are otherwise liable for, the infringement of Plaintiffs’ patent
`
`complained of herein, including but not limited to manufacturers, distributors, retail
`
`sellers, property owners, and/or individuals and entities that own and control these
`
`entities. Plaintiffs expect to amend the complaint to allege these JOHN DOES 1-30 and
`
`their capacities.
`
`JURISDICTION AND VENUE
`
`10.
`
`This action is a civii action arising under the patent laws of the United
`
`States.
`
`11.
`
`The jurisdiction of this Court arises under 28 U.S.C.§§ 1331 (federal
`
`question) and §§1338(a) and (b) (patent action).
`
`12.
`
`This Court has personal jurisdiction over Defendant Histologics
`
`because Histologics has established minimum contacts with the forum. Upon
`
`information and belief, Histologics manufactures (directly or indirectly through third
`
`party manufacturers) brush sample collection products that are and have been used,
`
`offered for sale, sold and purchased in New York which violates Plaintiffs’ patent rights.
`
`Upon information and belief, Histologics through its employees and agents offers for sale
`
`and/or sells its products in New York. In addition, Defendant Histologics regularly does
`
`andfor solicits business or engages in other persistent course of conduct or derive
`
`substantial revenue from goods used or consumer or services rendered in the State of
`
`New York that violate Plaintiffs’ patent rights or reasonably expect or should have
`
`expected the act of violating Plaintiffs’ patent rights to have consequences in New York,
`
`

`

`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 4 of 37 Page ID #:4
`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 4 of 37 Page ID #:4
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`and Histologics has derived substantial revenue from interstate commerce.
`
`13.
`
`This Court has personal jurisdiction over Defendant POPLAR because
`
`fOPLAR has established minimum contacts with the forum. Upon information and
`
`belief, POPLAR offers for sale and sells brush test products that are and have been used,
`
`offered for sale, sold and purchased in New York which violates Plaintiffs’ patent rights.
`
`Upon information and belief, POPLAR through its employees and agents offers for sale
`
`and/or sells its products in New York. In addition, upon information and belief,
`
`Defendant POPLAR has a clinical laboratory license issued by the State of New York
`
`authorizing it to offer its laboratory services and regularly does and/or solicits business or
`
`engages in other persistent course of conduct or derive substantial revenue from goods
`
`used and/or consumer services rendered in the State of New York that Violate Piaintiffs’
`
`patent rights or reasonably expect or should have expected the act of violating Plaintiffs’
`
`patent rights to have consequences in New York, and POPLAR has derived substantial
`
`revenue from interstate commerce.
`
`14.
`
`This Court has personal jurisdiction over MATTISON because
`
`MATTISON has established minimum contacts with this forum. Upon information and
`
`belief, MATTISON offers for sale and sells brush test products that are and have been
`
`used, offered for sale, sold and purchased in New York which violates Plaintiffs’ patent
`
`rights. Upon information and belief, MATTISON through its employees and agents
`
`offers for sale and/or sells its products in New York. In addition, upon information and
`
`belief, Defendant MATTISON has a clinical laboratory license to perform laboratory
`
`services and regularly does and/or solicits business or engages in other persistent course
`
`of conduct or derive substantial revenue from goods used and/or consumer services
`
`

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`Case 2:13-cv-O7909-DOC-RNB Document 1 Filed 04/26/13 Page 5 of 37 Page ID #:5
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`rendered in the State of New York that violate Piaintiffs’ patent rights or reasonably
`
`expect or should have expected the act of violating Plaintiffs’ patent rights to have
`
`consequences in New York, and MATTISON has derived substantial revenue from
`
`interstate commerce.
`
`15.
`
`Venue is proper in this district under 28 U.S.C. §§ 1391 (b), (c), and/or
`
`((1) and 28 U.S.C. §§ 1400(a) and/or (b), for the reasons, inter alia, that Defendants do
`
`business in this district and have committed acts of infringement in this district.
`
`16.
`
`On information and belief, Defendants’ activities constitute
`
`purposeful activities in New York in relation to the cause of action alleged.
`
`UNITED STATES PATENTS
`
`No. 6,258,044
`
`17.
`
`On or about Juiy 10, 2001, U.S. Patent No. 6,25 8,044 entitled
`
`APPARATUS AND METHOD FOR OBTAINING TRANSEPITHELIAL SPECIMEN
`
`OF A BODY SURFACE USING NON-LACERATING TECHNIQUE (the “‘044
`
`Patent”) was duiy and legally issued. Attached hereto as Exhibit 1 is a true and correct
`
`copy of the issued ‘044 Patent. Plaintiffs are currently the only owners of any and all
`
`rights and interests to the ‘044 Patent.
`
`18.
`
`Plaintiffs have the right to sue and recover for any and ail infringements of
`
`the ‘044 Patent.
`
`DEFENDANTS’ ACT OF INFRINGEMENT
`
`19.
`
`Upon information and beiief, on a date unknown to Plaintiffs, Histologics
`
`

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`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 6 of 37 Page ID #:6
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`began to manufacture, sell and continue to sell two products that infringe the ‘044 Patent
`
`throughout the United States and in this jurisdiction (the “Infringing Products”).
`
`Attached hereto as Exhibit 2 are printouts from Histologic’s website showing its
`
`Infringing Products. The infringing products are sample collection brushes which have
`
`bristles of sufficient stiffness to penetrate at least two layers of epithelial tissue in
`
`violation of the ‘044 Patent Claims, and Histologic’s instructions include use of the brush
`
`in the manner taught by the patent.
`
`20.
`
`Upon information and belief, on a date unknown to Plaintiffs, POPLAR
`
`began to offer for sale and sell the Infringing Products and still continues to offer for sale
`
`and sell the Infringing Products. Attached hereto as Exhibit 3 are examples of
`
`Histologic’s Infringing Products currently being offered for sale and sold by POPLAR.
`
`21.
`
`Upon information and belief, on a date unknown to Plaintiffs, Matfison
`
`began to offer for sale and sell the Infringing Products and still continues to offer for sale
`
`and sell the Infringing Products. Attached hereto as Exhibit 4 are examples of at least
`
`one of Histologic’s Infringing Products currently being offered for sale and sold by
`
`MATTISON.
`
`22.
`
`Despite due notice to Histologics of Plaintiffs’ rights, Histologics
`
`continues to infringe the rights of Plaintiffs, and such infringement is willful.
`
`FIRST CLAIM FOR RELIEF
`
`INFRINGEMENT OF ‘044 PATENT
`
`23.
`
`Plaintiffs repeat and reallege each allegation contained in paragraphs 1
`
`through 22 of this Complaint, as if again set forth at length.
`
`

`

`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 7 of 37 Page ID #:7
`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 7 of 37 Page ID #:7
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`24.
`
`Upon information and belief, Defendants have been making,
`
`using, and/or seiling without license or authority from Plaintiffs, in this district and
`
`elsewhere in the United States, the Infringing Products that embody the inventions
`
`claimed in the ‘044 Patent and are now infringing the ‘044 Patent under 35 U.S.C.
`
`271(a).
`
`25.
`
`Upon information and belief, Defendants have been manufacturing,
`
`offering for sale and selling products that embody the inventions claimed in the ‘044
`
`Patent.
`
`26.
`
`Upon information and belief, Defendants have and will continue to induce
`
`others, including but not limited to customers, to infringe the ‘044 Patent.
`
`27.
`
`Plaintiffs provided notice of its patent rights as set forth in the ‘044 Patent
`
`in fuli compliance with the provisions of 35 U.S.C. 287(3). Upon information and belief,
`
`Defendants will continue to infringe and induce infringement of the ‘044 Patent unless
`
`enjoined by this court.
`
`28.
`
`Plaintiffs have been damaged by the acts of infringements of the ‘044
`
`Patent committed by Defendants and will continue to be damaged by the infringements,
`
`unless the infringements by Defendants are enjoined by this court.
`
`29.
`
`Upon information and belief, Defendants have had actual knowledge of
`
`the specification and issued claims of the ‘044 Patent, and its continuing infringement of
`
`the “044 Patent is willful and deliberate.
`
`PRAYER FOR RELIEF
`
`WHEREFORE, Plaintiffs demand judgment against Defendants as follows:
`
`

`

`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 8 of 37 Page ID #:8
`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 8 of 37 Page ID #:8
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`(l)
`
`for Judgment that Defendants, their officers, agents, servants, employees,
`
`representatives, attorneys and all persons acting in active concert or participation with
`
`them, be found to have infringed the ‘044 Patent;
`
`(2)
`
`For an Order enjoining Defendants, their officers, agents, servants,
`
`employees, representatives, attorneys and all persons acting in active concert or
`
`participation with them from making, using, selling, or offering for sale products,
`
`services and/or product packaging which infringe the ‘044 Patent;
`
`(3)
`
`For an Order enjoining and restraining Defendants, their officers,
`
`agents, servants, employees, representatives, attorneys and ail persons acting in active
`
`concert or participation with them from inducing infringement of the ‘044 Patent;
`
`(4)
`
`That Plaintiffs be compensated for the damages caused by Defendants’
`
`infringement under 35 U.S.C. §284, in an amount to be precisely determined by an
`
`accounting, but not less than a reasonable royalty plus interest;
`
`a. That the award of damages for this exceptional case be trebled as
`
`provided by 35 U.S.C. §284;
`
`b. That Piaintiffs be awarded prejudgrnent interest, pursuant to 35 U.S.C.
`
`§ 284;
`
`c. That Plaintiffs be awarded its costs and attorneys fees incurred in
`
`prosecuting this action, including reasonably attorney’s fees, as
`
`provided for by 35 U.S.C. §285, (plus interest); and
`
`d. Such other and further relief as the court deerns just and equitable.
`
`(5)
`
`Ordering Defendants to turn over to the Court or to Plaintiffs or to destroy
`
`within ten (10) days from the entry of any Final Judgment or Preliminary Decree entered
`
`

`

`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 9 of 37 Page ID #:9
`Case 2:13-cv-O7909-DOC-RNB Document 1 Filed 04/26/13 Page 9 of 37 Page ID #:9
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`in this action, all property owned by Defendants which unlawfully violates the ‘044
`
`Patent, any infringing product literature owned by Defendants, and all other works owned
`
`by Defendants that infringe the ‘044 Patent, including an award of costs incurred by
`
`Plaintiffs for the destruction of said articles and product packaging.
`
`Plaintiffs demand a jury trial on all issues so triable.
`
`JURY DEMAND
`
`Dated: April 25, 2013
`
`LEVIS HN BERGER LLP
`By:
`
` Peter L. Berger (PB-012
`
`Tuvia Rotberg (TR-8787
`Jonathan Berger (JR—6448)
`11 Broadway, Suite 615
`New York, New York 10004
`Telephone (212) 486—7272
`Facsimile (212) 486—0323
`Email: Wan
`trotberg@llbl.com
`jberger@llbl.com
`
`Attorneys for Plaintiffs
`CDX LABORATORIES ENC. and
`SHARED MEDICAL
`
`RESOURCES, LLC
`
`

`

`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 10 of 37 Page ID #:10
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`
`
`
`
`10
`
`

`

`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 11 of 37 Page ID #:11
`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 11 of 37 Page ID #:11
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`I
`(12) United States Patent
`Lonky ct al.
`
`llllililmlllmllflllllllIHIIlllllllllllllllllllllilllIIIIIHIIIIIIHIH
`U8066258044B1
`
`(10) Patent No.:
`(45) Date of Patent:
`
`US 6,258,044 B1
`*Jul.10,2001
`
`(54) APPARATUS AND METHOD FOR
`OBTAINING TRANSEPI‘I‘HZELIAL SPECIMEN
`OFA BODY SURFACE USING A
`NON-MCERATING TECHNIQUE
`
`(75)
`
`Inventors: Nealm. Innkyflorba Linda, CA (US):
`Jeremy James Mlclmel Papndopoulos.
`Milwaukcc.W1(US)
`
`(73) Assignw: Omiswnm-ylon Joint Venlum.
`Sufl'am, NY(US)
`
`(*) Nance:
`
`This patent issued on a continued pros-
`eculiun applieaflon filed undcr 37 CFR
`153(0), and issubjecz [o the Iwenly war
`paienl
`term provisions of 35 U.S.C.
`154mm,
`
`Subjecl to any disclaimer, Ihe term of this
`patent is exlended or adjusted under 35
`U.S.C. 15403) by 0 days.
`
`(21) Appl. No: 09,660,425
`(22) Filed:
`“1.23, 1999
`Related 0.8. Application Data
`(60) vaisfoml application No. 60,093,910, filed on Jul. 23,
`1993.
`(51)
`Inl. Ch" IIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIIII.________ A6115 10100
`
`(52)
`13,3, (:1.
`__ 5001559,- 509/552
`(53) Field 01‘ Search ..................................... 5001552, 559,
`600/570; 604;“; 606/161; lSIDIG. 6, 206,
`207.2
`
`(56)
`
`Refemnces Cited
`
`US. PATENT DOCUMENTS
`
`411959 Nomiya 151164
`2,675,572 9
`611958 Macuan ........... 000/559
`2,039,049
`
`..... 600559
`1011950 Machan
`2,955,591
`
`4,227,531 - {011930 Suciue! 0.1.
`600569
`
`4,759,315 -
`711983 Siomby
`mrlss
`4,973,992 . 1011939 13959196001569
`
`511617.001
`5,067,195 ‘ 1311991 Sussman
`
`21'1993 Hicken ......
`5,104,626
`500/559
`5,251,182
`1011993 Luck u n].
`332/224
`5,623,941 " #1997 Hedbtrg e! sf.
`..................... 600/569
`5,713,369 '
`2:1998 Tao el al.
`.......
`600/569
`
`...... 15/206
`5,761,760 ’
`6/1998 Dumlerclal..
`011999 Gum: .................................. 1321213
`5,931,070 9
`
`9 cited by examiner
`
`Primary Exmnfner—Cary O’Conner
`[glisfimf Emufingrw-Chglwrinnorfil L
`no 1
`,
`e u, a
`‘
`'
`,
`£34333,” 2)! g a
`r m:
`owso n
`(57)
`ABSTRACT
`
`B
`
`,
`emer
`
`erger
`
`&
`
`A non-lacerational lcchniquc to coiled cells in an oral mouth
`cavity utilizes a bmsh with bdslles which have an abradjug
`surface and collect cells from the superficial, intermediate
`and basal 195m 05'1” ml “SSW-
`
`39 Clnlms, 8 melng Sheeis
`
`
`
`

`

`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 12 of 37 Page ID #:12
`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 12 of 37 Page ID #:12
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`US. Patent
`
`Jul. 10, 2001
`
`Sheet 1 of 8
`
`US 6,258,044 B1
`
`H “All
`
`

`

`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 13 of 37 Page ID #:13
`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 13 of 37 Page ID #:13
`
`U.S. Patent
`
`Jul. 10,2001
`
`Sheet 2 of8
`
`US 6,258,044 B1
`
`
`
`F76“. .3
`
`

`

`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 14 of 37 Page ID #:14
`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 14 of 37 Page ID #:14
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`US. Patent
`
`Jul.10,2001
`
`Sheet 3 of 8
`
`US 6,258,044 B1
`
`
`
`

`

`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 15 of 37 Page ID #:15
`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 15 of 37 Page ID #:15
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`US. Patent
`
`Jul. 10, 2001
`
`Sheet 4 of 3
`
`US 6,258,044 B1
`
`
`
`

`

`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 16 of 37 Page ID #:16
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`US Patent
`
`Jul. 10, 2001
`
`Sheet 5 of 3
`
`US 6,258,044 Bl
`
`
`
`

`

`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 17 of 37 Page ID #:17
`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 17 of 37 Page ID #:17
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`US. Patent
`
`Jui.10,2001
`
`Sheet 6 0f 8
`
`US 6,258,044'131
`
`70 v
`
`70
`
`80
`
`80
`
`72
`
`82
`
`F/G‘. 7
`
`[-76.8
`
`90
`A92
`kW):
`
`94
`
`H6. 9
`
`FIG. /0A
`
`26
`
`no
`
`96
`
`@112
`
`F/G. mt?
`
`

`

`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 18 of 37 Page ID #:18
`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 18 of 37 Page ID #:18
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`US, Patent
`
`Jul. 10, 2001
`
`Sheet 7 of8
`
`US 6,258,044 B1
`
`
`
`

`

`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 19 of 37 Page ID #:19
`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 19 of 37 Page ID #:19
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`US. Patent
`
`Jul. 10, 2001
`
`Sheet 8 of8
`
`US 6,258,044 B1
`
`
`
`

`

`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 20 of 37 Page ID #:20
`Case 2:13-cv-07909-DOC-RNB Document 1 Filed 04/26/13 Page 20 of 37 Page ID #:20
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`US 6,258,044 B1
`
`2
`surgically with either a scalpel or a laser so that a histologir
`cal section of the removed tissue can be prepared for
`microscopic evaluation. Histology can be generally defined
`as the microscopic inspection or other testing of a cross
`section of tissue. This prior art form of oral surgical biopsy
`is generally performed by a surgeon, and is often
`inconvenient, painful, and expensive. Furthermore, since the
`greatest number oforal cancers develop on the lateral border
`of the tongue and floor of the mouth,
`the difficulty and
`potential complications ofbiopsying these lesions, including
`pain, bleeding, and sear formation,-can be significant. Not
`infrequently, biopsy is delayed either by the patient due to
`fear of the procedure, or by the clinician due to technical
`difficulty in obtaining an adequate specimen.
`Since the majority of oral abnormalities detected clini-
`cally prove benign when tested microscopically, and given
`the limitations ofbiopsy, including cost, inconvenience, pain
`and potential for complications, relatively few oral lesions
`are subjected to biopsy. It is primarily for this reason that
`only oral lesions with clinical features strongly suggestiveof
`cancer or precancer are referred for biopsy as described in
`the prior art. As a result, many patients with ominous, but
`visually less suggestive lesions are allowed to progress to
`advanced oral cancer, with their condition undiagnosed and
`untreated.
`
`5
`
`JD
`
`15
`
`20
`
`25
`
`1
`APPARATUS AND METHOD FOR
`OBTAINENG TRANSEPITHELIAL SPECIEVIEN
`OFA BODY SURFACE USINGA
`NON-[ACERATENG TECHNIQUE
`
`This application claims the priority of U.S. provisional
`application Ser. No. 60/093,910 filed Jul. 23, 1993.
`FIELD OF THE INVENTION
`
`The present invention is directed to a method and apps-
`ratus for obtaining transepithelial specimens of body sur-
`faces using a non-lacerating technique. Specifically,
`the
`invention is directed to tools for sampling squamous epi-
`thelium from lesions found in the oral cavity and in similar
`body tissues. The invention is also directed to an improved
`method of testing all lesions that involve the epithelium of
`the oral cavity andfor similar body tissues.
`BACKGROUND OF THE [NVENTION
`
`Cancers of the oral cavity and pharynx are a major cause
`of death from cancer in the U.S., exceeding the U.S. death
`rates for cewical cancer, malignant melanoma and
`Hodgkin's diseaseAccording to the American CancerSoci-
`ety's Department of Epidemiology and Surveillance, an
`estimated 30,750 new cases of oral cancer were diagnosed
`in the U.S. during 1997, a ttgure which accounts for 2% to
`4% of all cancers diagnosed annually.
`Despite advances in surgery, radiation, and chemotherapy,
`the mortality rate of oral cancer has not improved in the last
`20 years. Ultimately, 50% of patients die from their
`malignancy, and 8,440 U.S. deaths were predicted for 1997.
`There are several reasons for the high mortality rate from
`oral cancer, but undoubtedly, the most significant factor is
`delayed diagnosis. Studies have demonstrated that the sur-
`vival and cure rate increase dramatically when oral cancer is
`detected at an early stage. For example, the 5-year survival
`rate for patients with localized disease approximates 79%
`compared to 19% for
`those with distant metastases.
`Unfortunately, approximately two thirds of patients at time
`of diagnosis have advanced disease, and over 50% display
`evidence of spread to regional lymph nodes and distant
`metastases.
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`in many body sites, but not the oral cavity, a technique
`known as cytology is commonly utilized as an alternative to
`performing a iacerating biopsy and histological evaluation.
`in these body sites, pro-cancerous and cancerous cells or cell
`clusters tend to spontaneously exfoliate, or "slough all"
`from the surface of the epithelium. These cells or cell
`clusters are then collected and examined under the micro-
`scope for evidence of disease.
`Since prior-art cytology is directed towards the micro-
`scopic examination of spontaneously exfoliated cells,
`obtaining the cellular sample is generally a simple, non~
`invasive, and painless procedure. Exfoliatcd or shed cells
`can often be obtained directly from the body fluid which is
`contiguous with the epithelium. Urine can thus be examined
`for evidence of bladder cancer, and sputum for lung cancer.
`Alternatively, exfoliated or shed cells may be obtained by
`gently scraping or brushing the surface of a mucus mem-
`brane epithelium to remove the surraunding murrus using a
`spatula or soft brush. This is the basis for the well known
`procedure known as the Pap smear used to detect early stage
`cervical cancer.
`
`Because of the ease by which a cellular sample can be
`obtained from these body sites, prior—art cytology is typi-
`cally utilized to screen asymptomatic populations for the
`presenceofearly stage disease. In the cervical Pap smear, for
`example,
`the entire surface area of the cervical regions
`where cancer generally occurs is gently scraped or brushed
`to collect and test the mucus from those regions. Abrasion of
`the underlying cervical epithelium is undesired, as it can
`cause bleeding and discomfort to the patient. This procedure
`is thus typically performed when no particular part of the
`cervix appears diseased, and when no suspect
`lesion is
`visible.
`
`”the design of prior art cytology sampling instruments
`reflects their use to sweep up cells which were spontane-
`ously exfoliated and present on the superficial epithelial
`surface. Since prior-art cytology brushes need only to gently
`remove surface material, they are designed of various soft
`materials which can collect the cervical mucous with mini-
`mal abrasion to the underlying epithelium. These cytology
`sampling instruments therefore either have soft bristles, soft
`
`Delay in the diagnosis of oral cancer is often the result of
`the limited diagnostic tools available in the prior art. The
`dentist or physician who detechr an oral lesion which is not
`clearly suggestive of a precancer or cancer clinically, and
`who is limited to the prior art tools and methods, is faced
`with a quandary. Approximately S—lfl'Zb of adult patients
`seen in a typical dental practice exhibit some type 'of oral
`lesion, yet only a small proportion (approximately 0.5% to
`1%) are precancerous or cancerous. These oral lesions are
`commonly evidenced as a white or reddish patch, ulceration,
`plaque or nodule in the oral cavity. The overwhelming
`majority of these lesions are relatively harmless; however,
`the multitude ofpoorty defined lesions in the oral cavity can
`be confounding to the clinician. A diverse group of oral
`lesions may be easily confused with malignancy, and
`conversely, malignancy may be mistaken for a benign
`,lcsion. Benign tumors, reactive processes, traumatic lesions,
`oral manifestations or systemic diseases, inflammatory oral
`disorders, and bacterial, viral and fungal
`infections all
`display similar oral features thereby impeding establishment
`of an accurate clinical diagnosis.
`The only reliable means currently available in the prior art
`to determine if a suspect oral lesion is pro-cancerous or
`cancerous. is to incise or exeise (in. tacerate) the lesion
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`US 6,258,044 B1
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`3
`flexible timhriated or fringed ends, or even, as in the case of
`the cotton swab or spatula, no bristles at all.
`Examples of prior art cytological sampling tools include
`the wooden, metal or plastic spatula. According to the
`traditional method of Pap smear sampling,
`the spatula is
`placed onto the surface of the cervix and lightly depressed
`or scraped across the surface of the cervix to pick up
`exfoliated cells.
`
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`all. Since priorvart cytology brushes only need to gently
`remove surface material, they are designed of various soft
`materials which can collect the cervical mucous with mini-
`mal abrasion to the underlying epithelium.
`While abnormal cells can spontaneously exfoliate to the
`epithelial surface and be gently removed by prior art instru-
`ments in the uterine cervix and other similar tissues, in many
`oral cavity lesions the abnormal cells never reach the surface
`because they are blockedby the keratin layer.Thls limitation
`is a major cause of the high false negative rate of prior art
`cytological testing to detect lesions of the oral cavity. 'llrat
`is, a large preportion of oral lesions found to be positive
`using lacerating biopsy and histology are found to be
`negative using cytology.
`In one major study,
`this false
`negative rate was found to be as high as 30%.
`It
`is largely due to this lack of correlation between
`histology and prior art oral cytology that there is currently no
`significant use of oral cytology in the United States or
`elsewhere to test questionable oral lesions. Since it is well
`known that dangerous, truly cancerous oral lesions may
`commonly be reported as “negative” using prior art cyto-
`logic sampling techniques, prior art cytologic techniques
`one: little as a reliable diagnostic alternative to the lacerat-
`lng biopsy and histology.
`SUMMARY OF THE INVENTION
`
`It is an object of the present invention to provide an
`apparatus and method for sampling epithelial cells from the
`anatomy without the pain or injury of lacerational biopsies.
`it is a further object of the present invention to provide an
`apparatus for sampling epithelial tissue in the oral cavity, the
`vulva, and similar keratinized epithelia.
`It is a bother object of the present invention to provide a
`non-lacerating apparatus for readily sampling cells from all
`levels of a surface epithelial lesion, including the basal,
`intermediate and superficial layers of the lesion.
`It is a further object of the present invention to provide an
`apparatus for sampling cells from the entire surface of a
`lesion, to completely sample a suspect lesion which may be
`multifocal.
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`Further examples of prior art cytological sampling tools
`include the Cytobrush®; a device which uses soft and
`tapered bristles to sample shed cells from the cervical canal.
`U.S. Pat. No. 4,759,376, which allegedly covers this
`product, likewise describes a conical tapered soft bristle
`brush (a mascara brush shape) which is placed into the
`cervical canal and rotated for endocervical sampling. U.S.
`Pat. No. 4,759,376 teaches that
`the bristles "are to be
`relatively soft such as that of a soil toothbrush to more
`readily bend and avoid damaging the tissues." By way of
`further example, physicians have long used the common
`swab, commercially known as the Q-Tip®,
`to perform
`endocervical sampling.
`Other prior art cytological sampling tools designed to
`obtain a cytological sample from the cervix may combine
`both cndorervical and exocervical sampling regions into one
`device. These devices swab the surface of mucous-covered
`tissue by soft brushing the mucous layer of the endocervix
`and exocervix at the same time, thereby collecting the cells
`contained in the mucous layer tissue of those surfaces. 'lhese
`devices include the Unimar®-Cervex Brush”, a brush that so
`has a contoured ital comb-litre head with a single layer of
`flexible plastic bristles (similar to a flat paint brush having
`only one row of bristles) in which the center bristles are
`longer than the bristles on the endsAccording to the method
`of use for the device, the center bristles are inserted into the
`cervical canal until the lateral bristles bend against
`the
`exoccrvix. The device is then removed and the cells are
`swabbed across a microscope slide similar to painting with
`a paintbrush.
`the Bayou Pap Brushm, which Medical
`Similarly,
`Dynamics,
`inc. represents is covered by 11.8. Pat. No.
`4,762,133, contains a center arm, made of soft DuPont
`bristles, running horizontal
`to the cervical canal and a
`second arm ofsol’t bristles at ninety degrees to the first arm,
`creating an L-sbape. 'Ihe center can is placed within the
`cervical canal and then rotated. Upon rotation,
`the soft
`bristles of thesccond arm automatically sweep the surface of
`the exocervix in a circular motion thereby sampling the
`exocervix along with the endocervix.
`Although cytology has been adopted [or use in several
`other body sites,
`it has not been found useful
`to test
`questionable lesions of the oral cavity. This is in large part
`due to the fact that the prior art devices and methods used to
`obtain a cellular sample for cytology are unsatisfactory
`when used to sample lesions of the oral cavity and similar
`epithelia. Unlike the uterine cervix, questionable lesions of
`the oral cavity and similar epithelia may be typically coated
`with multiple layers of keratiaizcd cells. This "keratin layer"
`forms a relatively hard "slain-like" coating over the surface
`of the lesion and may thus hide the abnormal cells lying
`underneath it and prevent their exfoliation from the surface.
`As noted above, the design ofprior art cytology sampling
`instruments reflect their use in tissues where spontaneously
`exfoliated abnormal cells are commonly present on the
`surface of an area of epithelium that harbors disease. These
`cytology sampling instruments therefore either have sol‘t
`bristles, soft flexible fimbriatcd ends, or even no bristles at
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`Further objects of the invention will become apparent in
`conjunction with the disclosure herein.
`In accordance with the present invention, an apparatus is
`provided for sampling all types of epithelium, particularly
`squamous epithelium, from lesions found in the oral cavity,
`the vaginal cavity, and other similar herallnized epithelia.
`Furth