Translation of Anti-CD22 Translation of Anti-CD22 Monoclonal Antibodies for the Monoclonal Antibodies for the

Treatment of LymphomaTreatment of Lymphoma

Joseph M. Tuscano, M.D.Joseph M. Tuscano, M.D.

Associate Professor of MedicineAssociate Professor of Medicine

Department of Internal MedicineDepartment of Internal Medicine

Division of Hematology and OncologyDivision of Hematology and Oncology

The Good, The Bad, and the UglyThe Good, The Bad, and the Ugly

OverviewOverview

• The GoodThe Good– The data and the RAID programThe data and the RAID program

• The BadThe Bad– UC Policy and PatentsUC Policy and Patents

• The UglyThe Ugly– Licensing, industrial partners, and the Licensing, industrial partners, and the ethicsethics

of it allof it all

Xenograft Trials/Mouse Numbers

Trial No Tx HB22.7 RIT

081500 5 4 9

101600 5 6 5

011601 _ 5 4

032701 _ 5 2

052401 3 _ 3

060401 5 5 _

071701 7 5 _

092101 4 _ _

102401 13 _ _

Total 42 30 23

0

100

200

300

400

500

600

700

800

900

1000

0 14 28 42 56 70 84

Da ys a fte r RIT

Tu

mo

r G

row

th (

Cu

bic

mm

.)

Untreated

anti-CD22 alone

RIT alone

0 14 28 42 56 70 840

200

400

600

800

1000

CD22 alone

RIT alone Untreated

Cu

bic

mm

.

Days after RIT

0 14 28 42 56 70 840

20

40

60

80

100

Untreated CD22 alone RIT alone

% S

urv

ivin

g

Day After RIT

Conclusions/SignificanceConclusions/Significance• CD22 ligand blocking mAbs have unique physiologic propertiesCD22 ligand blocking mAbs have unique physiologic properties

• CD22 ligand blocking mAbs are pro-apoptotic CD22 ligand blocking mAbs are pro-apoptotic

• They target lymphoma xenograftsThey target lymphoma xenografts

• They have independent lymphomacidal propertiesThey have independent lymphomacidal properties

• Augment the efficacy of RITAugment the efficacy of RIT

• Nontoxic alone and no additional toxicity with RITNontoxic alone and no additional toxicity with RIT

• mAb with therapeutic potential identified based on mAb with therapeutic potential identified based on targeting AND physiologytargeting AND physiology

Future StudiesFuture Studies• Additional xenograft studies with mAb (HB22.7) alone (increased Additional xenograft studies with mAb (HB22.7) alone (increased dose and schedule)dose and schedule)

• Xenograft studies with HB22.33Xenograft studies with HB22.33

• Additional signaling studiesAdditional signaling studies

• In vivo apoptotic studiesIn vivo apoptotic studies

• Humanization and human clinical trails with HB22.7Humanization and human clinical trails with HB22.7 via the Rapid Access and Intervention Drug (RAID) programvia the Rapid Access and Intervention Drug (RAID) program

• Licensing and support from Cellective TherapeuticsLicensing and support from Cellective Therapeutics

Types of Monoclonal AntibodiesTypes of Monoclonal Antibodies

Adapted fromAdapted from LoBuglio. LoBuglio. Crit Rev Oncol Hematol. Crit Rev Oncol Hematol. 1992;13:273.1992;13:273.

Human Murine Chimeric HumanizedHuman Murine Chimeric Humanized

What is RAID ?What is RAID ?RAID is a program designed to facilitate translation to RAID is a program designed to facilitate translation to the clinic of novel, scientifically meritorious the clinic of novel, scientifically meritorious therapeutic interventions originating in the academic therapeutic interventions originating in the academic community. It will do this by making available to the community. It will do this by making available to the academic research community, on a competitive academic research community, on a competitive basis, NCI resources for the pre-clinical development basis, NCI resources for the pre-clinical development of drugs and biologics. RAID is intended to remove of drugs and biologics. RAID is intended to remove the most common barriers between laboratory the most common barriers between laboratory discoveries and clinical trials of new molecular discoveries and clinical trials of new molecular entities. The goal of RAID is clinical "proof of entities. The goal of RAID is clinical "proof of principle" that a new molecule or approach is a viable principle" that a new molecule or approach is a viable candidate for expanded clinical evaluation.candidate for expanded clinical evaluation.

HB22.7 ChimerizationHB22.7 Chimerization

UC PolicyUC Policy

• Tech Transfer OfficeTech Transfer Office• Local vs. UCOPLocal vs. UCOP

• DisclosureDisclosure• When and WhyWhen and Why

• PatentsPatentsDifferent TypesDifferent Types

The Bayh-Dole ActThe Bayh-Dole Act

• What is the Bayh-Dole Act, what prompted it, What is the Bayh-Dole Act, what prompted it, and why is it important to university technology and why is it important to university technology transfer?transfer?

Enactment of the Bayh-Dole Act (P.L. 96-517), the "Patent and Enactment of the Bayh-Dole Act (P.L. 96-517), the "Patent and Trademark Act Amendments of 1980" on December 12, 1980 Trademark Act Amendments of 1980" on December 12, 1980 created created a uniform patent policy among the many federal agencies that a uniform patent policy among the many federal agencies that fund research. Bayh-Dole enables small businesses and nonprofit fund research. Bayh-Dole enables small businesses and nonprofit organizations, including universities, to retain title materials and organizations, including universities, to retain title materials and

products they invent under federal fundingproducts they invent under federal funding ..

The Bayh-Dole ActThe Bayh-Dole Act

• How has the Act influenced university technology How has the Act influenced university technology transfer over the last decade and what are the results?transfer over the last decade and what are the results?

Bayh-Dole gave universities control of their inventions. Bayh-Dole gave universities control of their inventions. By placing few restrictions on the universities' licensing By placing few restrictions on the universities' licensing activities, Congress left the success or failure of patent activities, Congress left the success or failure of patent licensing up to the institutions themselves.licensing up to the institutions themselves.

Tech Transfer OfficeTech Transfer Office

• The missionThe missionThe mission of university technology transfer/licensing offices The mission of university technology transfer/licensing offices is to transfer research results to commercial application for is to transfer research results to commercial application for public use and benefit.public use and benefit.

• Decides on patentabilityDecides on patentability• Markets patentsMarkets patents• Negotiates and administers licensesNegotiates and administers licenses• Oversight of patent prosecutionOversight of patent prosecution• Records incomeRecords income

Tech Transfer OfficeTech Transfer OfficeCont.Cont.

• InfluencesInfluences– a) a) the facultythe faculty--inventors, who often have expectations of research --inventors, who often have expectations of research

opportunities, income, public utilization and fame; opportunities, income, public utilization and fame; – b) b) the private sectorthe private sector, expectations of securing commercially viable , expectations of securing commercially viable

technology at a fair price; technology at a fair price; – c) c) the university administrationthe university administration, which expects the office to be self-, which expects the office to be self-

supporting and wants to prevent conflicts of interest; supporting and wants to prevent conflicts of interest; – d) d) the governing boardthe governing board, which needs assurance that the university's , which needs assurance that the university's

name and reputation are protected in its industrial relationships; name and reputation are protected in its industrial relationships; – e) e) the taxpayersthe taxpayers, with expectations that the office will manage state , with expectations that the office will manage state

and federal resources in an effective and nondiscriminatory manner; and federal resources in an effective and nondiscriminatory manner; and and

– f) f) the sponsoring agencythe sponsoring agency which insists on compliance with provisions which insists on compliance with provisions of the Bayh-Dole Act. of the Bayh-Dole Act.

PatentsPatents• Three typesThree types

– UtilityUtility– DesignDesign– PlantPlant

• DesignDesignUtility patentsUtility patents are granted for any new process, are granted for any new process,

methodmethod, machine, manufacture, or , machine, manufacture, or compositions of mattercompositions of matter, or any new and useful , or any new and useful improvement thereof.improvement thereof.

LicensingLicensing

(1)(1) What kind of licensing is most likely to lead to What kind of licensing is most likely to lead to rapid commercialization; and rapid commercialization; and

(2) What kind of licensing is in the public interest.(2) What kind of licensing is in the public interest.

(3) $$$(3) $$$

InfluencesInfluences

The Reality of Getting to Human The Reality of Getting to Human Clinical TrialsClinical Trials

• Composition of Mater patent held by DFCIComposition of Mater patent held by DFCI• Methods Patent held by UCD and DukeMethods Patent held by UCD and Duke• RAID subcontracted to Aires Biochemical companyRAID subcontracted to Aires Biochemical company

• Who owns the “right” to the humans antibodyWho owns the “right” to the humans antibody• Production issues have complicated translationProduction issues have complicated translation• My role as a university researcher and royalty recipient, principle My role as a university researcher and royalty recipient, principle investigator of human clinical trials, licensing company advisor investigator of human clinical trials, licensing company advisor and shareholder.and shareholder.

After ~ 15 years of development, so close yet so far from After ~ 15 years of development, so close yet so far from treating patients with cancertreating patients with cancer

JTJT

Clinical TrialsClinical TrialsGrant supportGrant support

Academic successAcademic success

$$$$

UCOPUCOP

LicensingLicensingPatent prosecution etcPatent prosecution etc

IndustryIndustry

$$$$$

LicensingLicensing

Partner/advisor Partner/advisor $$ + control$$ + control

DukeDuke

Patent/partnerPatent/partner

Collaboration/academicCollaboration/academicsuccesssuccess

$$$$$$$$$$****

LOST IN TRANSLATIONLOST IN TRANSLATION

Aeres/Aeres/ManufacturingManufacturing