Royalty Report: Drugs, Medical, Device – Collection: 282931

Selected Reagent means the Reagent that is selected by the Research Committee pursuant to the Research Program to be attached to the Therapeutic Agent by means of Pegylation.

Therapeutic Agent means human recombinant butyrylcholinesterase (BChE) having the amino acid sequence or having an amino acidsequence with 86% sequence identity to such human BChE sequence or a fragment of such a BChE and in each case which has activity of human recombinant butyrylcholinesterase (BChE).

Reagent means a PEG derivative used in the manufacture of a pharmaceutical or diagnostic product or medical device.

PEG means poly(ethylene) glycol or a derivative thereof.

Pegylation, with correlative meanings 'Pegylated' or to 'Peglate', means covalent chemical bonding of any Reagent (including Selected Reagent and including covalent chemical bonding through linking groups) with or to another material or materials. Such materials include, without limitation, proteins, peptides, oligonucleotides, other biomolecules, small molecules, therapeutic agents (including Therapeutic Agent), diagnostic agents, imaging agents and detectable labels. Additional materials that may be Pegylated include without limitation, polymers, liposomes, films, chemical separation and purification surfaces, solid supports, metal/metal oxide surfaces and other surfaces such as, by way of example but not limitation, those on implanted devices, and equipment, where a Reagent is covalently chemically bonded to one or more reactive molecules on the surface of such device or equipment. 'Pegylation' shall include the synthesis, derivatization, characterization, and modification of PEG for such purposes, together with the synthesis, derivatization, characterization, and modification of the raw materials and intermediates for the manufacture of Reagents (including Selected Reagent) or products (including Selected Product) incorporating such Reagent by means of covalent chemical bonding, and all methods of making and using each and all of the foregoing.

Licensor Patent Rights means all patents and patent applications (a) that are owned in whole or in part by Licensor, or licensed to Licensor, as of the effective date, (b) that become owned in whole or in part by Licensor at any time during the term, or (c) that are licensed to Licensor after the effective date, with the right to grant a sublicense, in each of the foregoing cases ((a), (b) and (c)), to the extent that such patents or patent applications are infringed (in the case of a pending patent application, would be infringed if granted) by making, having made, using, selling, offering to sell or importing Selected Product and/or the Selected Reagent in accordance with the terms of the license granted under this agreement.

Licensor Licensed Technology means, collectively, the Licensor patent rights and Licensor know-how.

Patent means: (i) any letters patent and utility models including any extension, substitution, registration, confirmation, reissue, supplemental protection certificate, re-examination or renewal thereof; and (ii) to the extent valid and enforceable rights are granted by a governmental authority thereunder, a patent application (and in each case any foreign counterpart thereto).

Patent Application means an application for letters patent, including a provisional application, converted provisional application, continuation application, a continued prosecution application, a continuation-in-part application, a divisional application, a re-examination application, and a reissue application (and in each case any foreign counterpart thereto).

The license granted under this Attachment is non-exclusive.

“Licensed Products” means Medical Products which are surface-treated with photo-reactive polyvinylpyrrolidone, photo-reactive heparin, diphoto diquat (photo-reactive crosslinking compound) or any combination of these photo-reactive reagents.

“Medical Products” means a single-use, temporary (less than 7 days) catheter placed within the vascular system that is designed, labeled and approved (as may be required by appropriate governmental authority prior to sale) for the purpose of in situ heating or cooling of blood. For the avoidance of doubt, such catheters shall not be designed, labeled or approved for the purpose of infusing or delivering any therapeutic or embolic agents or for the delivery or placement of permanently implantable therapeutic devices (including embolic devices), while the distal tip of such catheter resides at or above the common carotid artery. For purposes of this Attachment B1, saline solutions and contrast media (for placement or diagnostic purposes) are not considered therapeutic agents.

U.S. Patents
1.
METHOD OF IMPROVING THE BIOCOMPATIBILITY OF SOLID SURFACES

U.S.
Patent No. 4,973,493 issued 11/27/90

2.
BIOCOMPATIBLE COATINGS FOR SOLID SURFACES

U.S.
Patent No. 4,979,959 issued 12/25/90

3.
PREPARATION OF POLYMERIC SURFACES VIA COVALENTLY ATTACHING POLYMERS

U.S.
Patent No. 5,002,582 issued 3/26/91

4.
BIOMOLECULE ATTACHMENT TO HYDROPHOBIC SURFACES

U.S.
Patent No. 5,217,492 issued 6/8/93

5.
METHOD OF BIOMOLECULE ATTACHMENT TO HYDROPHOBIC SURFACES

U.S.
Patent No. 5,258,041 issued 11/2/93

6.
BIOCOMPATIBLE DEVICE WITH COVALENTLY BONDED BIOCOMPATIBLE AGENT

U.S.
Patent No. 5,263,992 issued 11/23/93

7.
RESTRAINED MULTIFUNCTIONAL REAGENT FOR SURFACE MODIFICATION

U.S.
Patent No. 5,414,075 issued 5/9/95

8.
SUBSTRATE SURFACE PREPARATION

U.S.
Patent No. 5,512,329 issued 4/30/96

9.
PREPARATION OF CROSSLINKED MATRICES CONTAINING COVALENTLY IMMOBILIZED CHEMICAL SPECIES AND UNBOUND RELEASABLE CHEMICAL SPECIES

U.S.
Patent No. 5,563,056 issued 10/08/96

10.
RESTRAINED MULTIFUNCTIONAL REAGENT FOR SURFACE MODIFICATION

U.S.
Patent No. 5,637,460 issued 6/10/97

11.
PHOTOACTIVATABLE WATER SOLUBLE CROSSLINKING AGENTS CONTAINING AN ONIUM GROUP

U.S.
Patent No. 5,714,360 issued 02/03/98

U.S. Patent Applications
1.
VIRUS INACTIVATING COATINGS

Filed 6/7/95
2.
METHOD AND IMPLANTABLE ARTICLE FOR PROMOTING ENDOTHELIALIZATION

Filed 5/26/95

Foreign Patents
1.
IMPROVEMENT OF THE BIOCOMPATIBILITY OF SOLID SURFACES

Canadian Patent No. 1305068, issued 7/14/92
Australian Patent No. 615637, issued 10/16/87
EPO Patent No. 0326579, issued 1/11/95
2.
BIOMOLECULE ATTACHED TO A SOLID SURFACE BY MEANS OF A SPACER AND METHODS OF ATTACHING BIOMOLECULES TO SURFACES

Canadian Patent No. 1335721, issued 5/30/95

Foreign Patent Applications
1.
BIOCOMPATIBLE COATINGS

Filed in Canada, Europe, Japan, Denmark, and Norway
2.
PREPARATION OF POLYMERIC SURFACES

Filed in Canada, Europe, Japan, Denmark, and Norway
3.
IMMOBILIZATION OF CHEMICAL SPECIES IN CROSSLINKED MATRICES

Filed in Canada, Europe, Australia, Japan
4.
IMPROVEMENT OF THE BIOCOMPATIBILITY OF SOLID SURFACES

Filed in Japan
5.
RESTRAINED MULTIFUNCTIONAL REAGENTS FOR SURFACE MODIFICATION

Filed in Canada, Europe, Australia and Japan

Licensor shall grant a sole license, with the right to grant sublicenses, under those rights Licensor has to the Enzon Patents, solely to develop, make, have made, use, import, offer for sale and sell in the territory that version of the Product that uses Reagent to covalently bond to the active molecule in Licensees-001 Product and has a branched backbone structure with two (2) arms and a molecular weight of 40K daltons.

Licensor shall grant, for the sole purpose of, and with respect to and only with respect to, the manufacture, use, sale, offer for sale, and importation in the territory of that version of the Product that uses Reagent to covalently bond to the active molecule in Licensees-001 and has a branched backbone structure with two (2) arms and a molecular weight of 40K daltons, a non-exclusive license under those rights Licensor has: to patents or patent applications ( other than the Enzon Patents) owned or controlled by Enzon or the Enzon affiliates; and all patent claims owned or controlled by Enzon or the Enzon affiliates that are not within the Enzon Patents;  issue from any patent application filed after January 7, 2002; and claim the composition, manufacture, or use of that version of the Product that uses Reagent to covalently bond to the active molecule in Licensees-001 and has a branched backbone structure with two (2} arms and a molecular weight of 40K daltons.

For the Manufacture and Supply of the Reagent Exclusivity, Licensor will manufacture and supply one hundred percent (100%) of Licensees, its affiliates and sublicensees purchase requirements of the Reagent for the manufacturing of the Product.  Licensee, its affiliates and sublicensees will purchase the Reagent exclusively from Licensor for the manufacture of the Product.

The license granted excludes patent claims owned or controlled by Enzon or the Enzon affiliates that claim the composition of matter of an un-pegylated active molecule, methods of making an un-pegylated active molecule, or methods of using an un-pegylated active molecule (other than a claim to a method of pegylating an unpegylated active molecule), even if such active molecule is contained in or is part of the Product.

PEG shall mean poly (ethylene glycol).  Pegylation / Pegylated, shall mean covalent chemical bonding of polyethylene glycol.

Product shall mean a product produced by linking Licensees-001 to the Reagent.  Licensees-001 is a vascular endothelial growth factor antagonist.

Reagent shall mean N-Hydroxysuccinimide ester of bis-<Methoxypoly(ethylene glycol} MW 20.0000}-modified lysine (mPEG2NHS 40K}.

Technology relates to the pegylation of Macugen that occurs by linking a reagent supplied by Licensor to the active pharmaceutical ingredient.

Licensor grant to Licensee an exclusive worldwide license, with a right to grant sublicenses, under their rights in and to the Licensor X-Patents and under their interests in Licensee X-Patents to make, have made, use, sell, offer for sale, have sold and import certain X-Compounds, which X-Compounds contain a para-C1-C4-alkoxy substituted phenyl or pyridyl group in the place of 'Ar' as in formula (I) of WO 98/03510 and formula (I) or WO 97/29109 where such phenyl or pyridyl group is otherwise freely substituted and which X-Compounds otherwise specifically do not include a total of ten (10) compounds which may be named by Licensor in writing to Licensee within six (6) months of the Effective Date and provided that said specifically named ten (10) compounds were not previously made by an employee of Licensee in a written record before said naming by Licensor or which  may be named by Licensor in writing to Licensee after six (6) months and before twelve (12) months of the Effective Date and provided that said specifically named ten (10) compounds were not previously named by an employee of Licensee in a written record before said naming by Licensor.

X-Compounds means compounds which, as compounds or chemical entities, are specifically or generically within  the published claims of WO 98/03510 or which are specifically or generically within the published claims of WO 97 /29109 and which is a pyrazolopyrimidine having a base structure.  For clarity and in accordance with the foregoing, an X-Compound is not and does not include those compounds described in WO 98/03510 as pyrazolotriazines wherein A in formula (I) therein is a nitrogen (N) atom.

Licensee X-Patents means the rights granted by any governmental authority under a Patent derived from from WO 98/03510 and any counterparts  thereof, and  additionally, the rights  granted by any governmental authority  under a Patent which claims an X-Compound as a novel compound or chemical entity, which Patent is owned or Controlled by Licensee at any time.

Licensee X-Patents licensed to Licensor under this Article will be considered by Licensor a Program Patent under the agreement between Licensor effective January 1, 1995 for the purpose of determining the rights therein and the obligations therefor as between Licensor only.

Patent means (i) valid and enforceable letters patent including any extensions, registration, confirmation, reissue,  continuation, divisional, continuation-in-part, re-examination, or renewal thereof, and (ii) pending applications for letters patent.

Product means any form or dosage of a compound for pharmaceutical use in humans or other animals or for use as a diagnostic tool that consists of an X-Product or N-Product, as the case may be.

N-Product means a Product comprised of an N-Compound.

N-Compounds means those compounds which, as compounds or chemical entities, are specifically or generically within the scope of the published claim number 4 of WO 98/35967 and includes those compounds as described in the disclosure of WO 98/35967 and shown as substructures (II) and as (Ila), (Ilb) and (lie).

This license granted for Laser Angioplasty Catheters is non-cancelable by Licensee during the period from the Effective Date through June 30, 2009.

This license granted for Non-Laser Functioning Catheters and Guidewires for use with Licensees Laser Therapy Systems is non-exclusive.

The Licensed Products means Medical Products that are surface-treated with photoreactive polyvinylpyrrolidone copolymer, non-photoreactive polyvinylpyrrolidone, photoreactive polyacrylamide copolymer, one or more of the photoreactive crosslinking agents known to the parties as PR01 and PR04, a compound for promoting polymer-to-metal adhesion known to the parties as TL03, or any combination of these compounds, for the purpose of providing a lubricious surface to the Medical Products.

MEDICAL PRODUCTS-B1 Laser Angioplasty Catheters:
The Medical Products means excimer laser angioplasty catheters specifically adapted for coronary and peripheral use. Medical Products includes Licensees chronic total occlusion laser angioplasty catheters.

MEDICAL PRODUCTS-B2 Non-Laser Functioning Catheters and Guidewires for use with Spectranetics Laser Therapy Systems:
The Medical Products means the following Licensee-labeled non-laser functioning catheters and guidewires for Licensees laser therapy system that are specifically designed and labeled for use solely with laser angioplasty catheters: (I) BIAS sheath, (ii) support catheters, (iii) cardiac lead locking device, and (iv) chronic total occlusion steerwires.  Medical Products does not include catheters for (I) infusion of diagnostic, therapeutic, or embolic agents in the neurovascular region, or (ii) insertion of therapeutic embolic devices in the neurovascular region. Medical Products does not include catheters used to deliver stents of any type.

Licensor grant to Licensee an exclusive worldwide license, with a right to grant sublicenses, under their rights in and to the Licensor X-Patents and under their interests in Licensee X-Patents to make, have made, use, sell, offer for sale, have sold and import certain X-Compounds, which X-Compounds contain a para-C1-C4-alkoxy substituted phenyl or pyridyl group in the place of 'Ar' as in formula (I) of WO 98/03510 and formula (I) or WO 97/29109 where such phenyl or pyridyl group is otherwise freely substituted and which X-Compounds otherwise specifically do not include a total of ten (10) compounds which may be named by Licensor in writing to Licensee within six (6) months of the Effective Date and provided that said specifically named ten (10) compounds were not previously made by an employee of Licensee in a written record before said naming by Licensor or which  may be named by Licensor in writing to Licensee after six (6) months and before twelve (12) months of the Effective Date and provided that said specifically named ten (10) compounds were not previously named by an employee of Licensee in a written record before said naming by Licensor.

X-Compounds means compounds which, as compounds or chemical entities, are specifically or generically within  the published claims of WO 98/03510 or which are specifically or generically within the published claims of WO 97 /29109 and which is a pyrazolopyrimidine having a base structure.  For clarity and in accordance with the foregoing, an X-Compound is not and does not include those compounds described in WO 98/03510 as pyrazolotriazines wherein A in formula (I) therein is a nitrogen (N) atom.

Licensee X-Patents means the rights granted by any governmental authority under a Patent derived from from WO 98/03510 and any counterparts  thereof, and  additionally, the rights  granted by any governmental authority  under a Patent which claims an X-Compound as a novel compound or chemical entity, which Patent is owned or Controlled by Licensee at any time.

Licensee X-Patents licensed to Licensor under this Article will be considered by Licensor a Program Patent under the agreement between Licensor effective January 1, 1995 for the purpose of determining the rights therein and the obligations therefor as between Licensor only.

Patent means (i) valid and enforceable letters patent including any extensions, registration, confirmation, reissue,  continuation, divisional, continuation-in-part, re-examination, or renewal thereof, and (ii) pending applications for letters patent.

Product means any form or dosage of a compound for pharmaceutical use in humans or other animals or for use as a diagnostic tool that consists of an X-Product or N-Product, as the case may be.

N-Product means a Product comprised of an N-Compound.

N-Compounds means those compounds which, as compounds or chemical entities, are specifically or generically within the scope of the published claim number 4 of WO 98/35967 and includes those compounds as described in the disclosure of WO 98/35967 and shown as substructures (II) and as (Ila), (Ilb) and (lie).