Document:

Agreement , dated July 6, 2001, between Da Vinci Biomedical & Phage Biotechnolog

 Exhibit 10.10 
  

			
	DaVinci Biomedical Research Products, Inc.	 	[LOGO]
	 PO BOX 1125
	 
	 SOUTH LANCASTER, MA 01561
	 

  

			
	 TO:
	  	 SHIP TO:

		
	 Phage Biotechnology
	  	 Phage Biotechnology

	 Att. Accounts Payable
	  	 Dr. Jack Jacobs

	 18300 Von Karman Ave. Suite 440
	  	 14270 Franklin Ave. Suite 110

	 Irvine, CA 92612
	  	 Tustin, CA 92780

  
 INVOICE -PH1000

  

											
	 CUSTOMER ORDER NO.
	  	INVOICE DATE	  	DATE SHIPPED	  	SHIPPED VIA	  	 F.O.B.
	  	TERMS
	 6005
	  	7-6-01	  	N/A	  	N/A	  	 50%prior/50%.upon comp

	 QUANTITY
                    DESCRIPTION
	  	 	  	UNIT PRICE	  	 TOTAL AMOUNT

  

	
	This regard previous invoice!!!
	
	Adjusted quote per Dr. Jacobs on 7-6-01. An addictional 10 of 12 animals will be used of which will increase the total number of animals to 37 of which 31 would be the minimum number of
canine used! I altered our original GLP quote to the price of $160,578. A reduction of 12.56%. If we take $180,578 (original price) and increase by 48%( 12 addictional canines) then we would get $267,255.44. If I give you the same decrease as
before, -12.56%, we get $237,433.75. ( As a reference; a reduction of $29,821.69).

  
  
 Total Revised GLP: $237,433.75 
  
 50% due prior to ordering of Canine. $118,716.87 
 50% due upon completion. $118,716.87 
  
 Any
questions... call or fax us at Tel. 978-368-3477 or Fax. 978-368-3579 

 Total Revised GLP: $237,433.75 
  
 TERMS & CONDITIONS 
  

			
	Comments:	 	For Pathology: If you would like Digital or standard pictures, for future reference, please, advice. Pathology will be conducted on all abnormal findings when other organs are viewed during
necropsy. This may increase costs!
		
	Charges:	 	1) A change in procedure, quantities, protocol, abnormalities and time needed, et may also change costs. We normally do not change cost for minor changes. They would have to be
significant!
		
	Time:	 	Per discussion and agreement between Mr. J. Villani of DaVinci and Dr. Jack Jacobs. Note: The sooner it is known, when the project will begin, the better it will be to schedule canines to be
delivered and set-up in there own holding room!
		
	Terms:	 	Payment of 50% prior to procedures and 50% upon completion.
		
	Cancellation
Policy:	 	In the event that the sponsor can not perform the project on the day scheduled and needs to cancel the date, a cancellation fee of $1,500 per day will be charged to the sponsor unless
cancellation of day is conveyed two weeks in advance. In the event that the project is canceled, all Animals, material purchased for project, labor, et, will be charged to client.

  

					
	Da Vinci Biomedical Research Products, Inc.
			
	 Mr. Joseph Villani:
 Sales Executive
	  	  

	 	  

	  	Signature	 	Date
			
	 Mr. Mario Pio Villani:
 Surgical Specialist
	  	  

	 	  

	  	Signature	 	Date
			
	 Dr. Jack Jacobs:
 Project MGR
	  	  

	 	  

	  	Signature	 	Date

 DaVinciTM 
 Biomedical research Prod.

  
 PROTOCOL 
  
 ACTIVITY INVOLVING VERTEBRATE ANIMAL MODELS 
  
 Cardiotoxicity Study of Fibroblast Growth Factor (FGF-1) in Dogs 

 
 DaVinci Study Number: DB-19 
  

					
	Sponsor:	 	 Cardio Vascular Genetic Engineering Corp.
 Phage Biotechnology Corp.
 14270 Franklin Ave. Suite 110
 Tustin, CA 92780

		
	 	 	 Telephone Number: 714-368-1520, ext.15
 Fax
Number: 714-368-1517

		
	Sponsor Contact:	 	Jack Jacobs
		
	e-mail Address:	 	jjacobs@phagebiotech.com
		
	Project Site:	 	DaVinci Biomedical Research Products
	 	 	40 Maple Ave
	 	 	So. Lancaster, MA 01561
			
	 	 	Telephone Number:	 	 (978) 368-3477

	 	 	Fax Number:	 	 (978) 368-3579

		
	Facility Contact Person:	 	Mario Pio Villani
		
	Protocol Issue Date:	 	July 13, 2001

  

			
	 DaVinci Biomedical Research ProdTM
	  	 
	Cardiotoxicity Study of Fibroblast Growth Factor (FGF-1) in Dogs	  	 July 13, 2001

	 Study Number: DB-19
	  	 Page 2 of 11

  
 1. OBJECTIVE/LAY SUMMARY: The
objective of this study is to evaluate the toxicity that may occur during a 3-28 day post-dosing period following the acute administration of FGF-1 directly into the ischemic heart of a dog. 
  
 2. REGULATORY REFERENCE: This study will be performed under Good Laboratory Practice
Regulations; The Standard Operating Procedures of the test facility will be followed, and all appropriate study documentation’s will be maintained in the study file. 
  
 3. STUDY DESIGN: During the ischemic insult and dose administration procedure the following values will be obtained every 10-15
minutes: electrocardiograms (ECG’s), heart rate (HR), systolic arterial pressure(SAP), diastolic arterial pressure(DAP), and mean arterial pressure(MAP) will be monitored and recorded, BP and ECG changes occur during ischemic insult, or any
time thereafter including dose administration, values will be monitored until baseline values are established, but not to exceed 30 minutes post. A printout of ECG’s will be performed when values change and every 10-15 minutes, thereafter.

  
 The following groups of animals will be used on study: 
  

							
	 Group 1
	  	 Vehicle
	  	 5 dogs (3male and 2female)
	  	 28 day post-dosing necropsy

	 Group 2
	  	 0.02 mg/kg FGF
	  	 5 dogs (3male and 2female)
	  	 28 day post-dosing necropsy

	 Group 3
	  	 0.2 mg/kg FGF
	  	 5 dogs (3male and 2female)
	  	 28 day post-dosing necropsy

	 Group 4
	  	 Vehicle
	  	 3 dogs (2male and 1female)
	  	 3 day post-dosing necropsy

	 Group 5
	  	 0.2 mg/kg FGF
	  	 3 dogs (2male and 1female)
	  	 3 day post-dosing necropsy

  
 Treatment Regimen: 

 
 Each dog will receive an ischemic insult to the heart, using a balloon-tipped catheter,
where injury and thrombus formation are directed at the left circumflex coronary artery. The ischemic insult will be monitored angiographically and by electrocardiograms. The animals will have a 7 day recovery period prior to dosing with the test
article or vehicle. The total dosage is given. Each animal will receive two injections of FGF-1, one injection in the general area of the ischemic insult and one injection in healthy heart tissue, Group 2 will receive two injections of 0.02 mg/kg
FGF-1 and group 3, two injections of 0.2 mg/kg FGF-1. The injections of the vehicle or test article will be made directly into the cardio-ventricular wall via a mini-thoracotomy. The volume of each injection will be 0.25 ml and will contain the
growth factor and heparin in a physiologic salino solution. The amount of heparin in each injection will at a fixed ratio of 1000 IU heparin/mg FGF-1, the same as will be used in the proposed clinical trial. The Sponsor will include the heparin in
each dose and in the vehicle. Both the high and low dose of heparin will be represented in the vehicle groups. 
  
 Cardiovascular Measurements: 
  

	1.	Angiograms: A total of 4 angiograms will be performed on each dog including a base-line angiogram, one after the ischemic insult, one after dosing of vehicle or test substance and
one prior to necropsy. 

			
	 Davinci Biomedical Research ProdTM
	  	 
	Cardiotoxicity Study of Fibroblast Growth Factor (FGF-1) in Dogs	  	 July 13, 2001

	 Study Number: DB-19
	  	 Page 3 of l1

  

	2.	Electrocardiograms (ECG’s): Baseline prior to procedure, post coronary occlusion, prior to dose administration, and post administration 3-5 days, and prior to necropsy.

  
 Blood Draws For Assays: Blood will be drawn at the
following times to permit measurement of assays to assess cardiac damage and for PK studies by the Sponsor. Pre-ischemic time point, post-ischermic time points at 7 days, and post-dosing time points of: 30 min, 1, 3, 6, 24 hours, day 3 and 7 and
then weekly during the post-dose observation period. Blood will be obtained via the jugular or other suitable vein and shipped on dry or wet ice to 1) contract lab to perform the cardiac enzyme as says, and 2) Sponsor. A 2.5 ml sample in serum
separator tube. The Sponsor will be notified before any samples are shipped to verify the number of samples to be analyzed. 
  
 The following cardiac enzyme assays will be diagnosed: 
  

			
	 1. Creatine phosphokinase
 (CK)
	  	 Shipped frozen to Ani-Lytics

	     Total [creatine kinase]
     Cardiac [CK(MB)]
	  	 
		
	 2. Lactate Dehydrogenase
	  	 
	 (LDH)
	  	 Shipped on wet ice to Ani-Lytics

	     Total                 [Lactate
Dehydrogenase]
	  	 
	 	  	 
	     Cardiac [LDH(CH4)]
	  	 

  
 Clinical Blood Draws:

  
 The following blood samples will be
collected: 
  
 CBC, Clinical Chemistry. 1.8ml serum separation, and 0.5ml EDTA
sample will be taken. 
  
 Timepoints: Prior to surgery, post ischemia, day
1 post test article administration, and pre-necropsy. 
  
 Parameters:
Kidney- BUN, and Creatinine, Liver- ALT, AST, Alkaline phosphatase, and total Bilirubin, 
  
 Eye examinations: The eyes of all animals will be examined using an indirect ophthalmoscope and slit lamp microscope to check for any signs of angiogenesis in the eyes. The examinations will be performed
prior to dosing and prior to necropsy. 
  
 Rationale for using animals:

  
 Written Narrative Description for Alternatives to Painful
Procedures. References: Animal Welfare Act section 3(a)(B) and 9CFR, and Part 2 section 2.31(d, 1, and ii). 
  
 a. Animal Species: 
  
 This product requires evaluation of using in vivo model, as its anticipated use will be in humans. Dogs are an established animal species for
cardiovascular and pharmacokinetic studies. There are no alternatives to intact animal models in conducting myocardial infarction studies such as these. A MedLine search of over 11 million citations revealed no similar studies have been performed in
the past. pharmacokinetic studies. There are no alternatives to intact animal models in conducting myocardial infarction studies such as these. 

			
	 DaVinci Biomedical Research ProdTM
	  	 
	Cardiotoxicity Study of Fibroblast Growth Factor (FGF-1) in Dogs	  	 July 13, 2001

	 Study Number: DB-19
	  	 Page 4 of 11

  

	 	b.	Number of Animals: Thirty seven animals is the minimum needed to show statistical significance, and allows 6 additional animals for experimental error associated with this
model. 

  

	 	c.	Level of Discomfort and/or Pain: Please check one of the following, 

  
  ̈ B. very low, temporary
pain or discomfort 
  
 x
C. Short term pain and/or discomfort(surgical procedure-use of analgesic, anesthetic and tranquilization drugs to eliminate or minimize discomfort and pain) 
  
  ̈
D. chronic pain (anesthetics and analgesic to be provided) 
  
  ̈ E. procedures with the involvement of pain (where pain can not be eliminated) 
  

	 	d.	If C,D&E of section c are chosen have you looked at alternatives and if no alternatives give explanation?( Narrative Description Needed) 

  

	4.	TEST SYSTEM: The procedure described will be performed in accordance to the Standard Operating Procedure of the Test Facility. 

  

	 	A.	Animals: Animals may be referred to by tattoo, species, or animal number in study file. 

  
 Common Name: Dog (beagle) 
 Species: Canis familiaris 
 Number of Males: 21 
 Number of Females: 16

 Age of Onset: Documented on file 
 Weight at Onset: Documented on file 
  

	 	B.	Source: Animals will be obtained from test facilities certified vendors and will be documented on study file. 

  

	 	C.	Quarantine: Animals will be quarantine for seven days, and released by the veterinarian after physical exam. 

  

	 	D.	Randomization: Randomization of animals for treatment will be done by random number selection. 

  

	 	E.	Identification: Each animal will be identified tattoo. That will also be posted outside the animals cage and/or enclosure. 

  

	 	F.	Disposition of Animals: At the conclusion of the study the animals be euthanized in accordance with the AVMA panel on Euthanasia,218 (5): 668-696, 2001.

			
	 DaVinci Biomedical Research ProdTM
	  	 
	Cardiotoxicity Study of Fibroblast Growth Factor (FGF-1) In Dogs	  	 July 13, 2001

	 Study Number: DB-19
	  	 Page 5 of 11

  

	5.	ANIMAL CARE PROCEDURE: The procedures described and performed below will be conducted in accordance with the Guide for the Care and Use of Laboratory Animals, USDA, APHIS,
Animal Welfare Act and/or in accordance with the Standard Operating Procedures of DaVinci Biomedical Research Prod. 

  
 A. Animal Husbandry and Maintenance: Animals will be individually housed during the test period. During the holding and testing period husbandry
maintenance and environmental conditions will be maintained as in the quarantine period, unless changes are needed which will be noted in the protocol. 
  
 B. Environmental Conditions: The conditions in the room will be maintained as follows: room temperature will be maintained 64-84deg F and the
humidity will range 30-70%, and the room will have 12/12 light/dark cycle. 
  
 C. Water: Tap water will be provided to the animals ad libitum (unless the animal is being fasted. Water analysis will be performed biannually and made available for the study file. Water will be analyzed by an
independent contract facility. The results will include the following: heavy metals, chlorinated hydrocarbons, organophosphates, nitrates, nitrites, total trihalomethanes, dissolved minerals, and a standard plate count. 
  
 D. Diet: LabChows, Lab Diet. Certified Canine Chow Brand will be fed
to the animal daily. The lot and expiration will be documented and recorded on file. Chow may differ if specified by sponsor. 
  

	6.	TECHNICAL PROCEDURES: The procedures described will be performed in accordance will the Standard Operating Procedures of DaVinci Biomedical Research Prod. Data collected will
be documented manually. 

  
 A. Body Weights:
Individual body weights will be recorded prior to surgery on the surgery form and prior to necropsy. 
  
 B. Fasting of Animals: All animals will be fasted at least 12-24 hours prior to surgery((NPO) no food or water). 
  
 C. Preoperative Procedure: 
  
 Anesthesia: Each animal will be anesthetized with butorphenol
(0.2mg/kg), acepromazine (0.1mg/kg), and atropine (0.02 mg/kg) IM as a pre-medicated cocktail and then Propofol will be administered at 4 mg/kg IV for anesthesia at a rate of 1ml/10kg/min prior to surgery preparation. The animal will be immediately
intubated and maintained under anesthesia with inhalant isoflurane anesthetic at 2.5%-4% for induction and 0.5-2.5% for maintenance delivered through either a volume-regulated respirator or rebreathing apparatus. An intravenous catheter will be
placed in a peripheral vessel for 

			
	 DaVinci Biomedical Research ProdTM
	  	 
	Cardiotoxicity Study of Fibroblast Growth Factor (FGF-1) in Dogs	  	July 13, 2001
	 Study Number: DB-19
	  	Page 6 of l1

  
 drug administration
if needed, and Lactated Ringer solution to be administered at l0ml/kg/hr. If emergency drugs are needed they will be administered through this line and the drug, dose, route, and site of administration will be documented in the surgical file.

  
 Surgical Preparation: The animal will be clipped over
the femoral artery and will be positioned supine. The operative area will be cleaned with a three alternating scrubs of povidone-iodine scrub and 70% alcohol, once the alternating scrubs are done a final application of povidone-iodine solution will
be applied and allowed to dry. (the area will be draped for aseptic surgery). 
  
 D-1. Surgical Procedure: 
  
 Induced myocardial ischemia: Once the surgical site has been aseptically draped and is prepared for surgery a Slazenger needle will be used to make an arteriotomy into the femoral artery, upon successful insertion into the artery a
guide wire will be introduced through the needle into the artery, the needle will be removed and the introducer will be placed over the guide wire into the artery. With the use of an Angio-catheter and fluoroscopic guidance the catheter will be
advanced up and over the aortic arch and into the ostia and placement will be confirmed by coronary arteriogram with contrast media (MD-76, Mallinkrodt Medical) of the left coronary artery. A guide-wire will be used to advance into the circumflex
artery and an appropriate sized balloon will be used to advance over the guidewire to the position of choice. The balloon will be expanded and the intimal layer of the artery will be injured, this will be performed by push-pull mechanism. Post
injury the balloon will be deflated and withdrawn from the injury site, and will be inflated distally to acquire stasis. Occlusion will occur quickly and a pre and post ischemic image will be taken. 
  
 E. Postoperative Procedures: Post surgery the surgical sites will be
monitored and checked once daily for any evidence of infection, bleeding dehiscence, or swelling. 
  

	 	1)	Recovery: The animal will be allowed to recover from anesthesia, and the animal will be extubated when the swallowing reflex has returned. 

  

	 	2)	Postoperative Analgesia: If needed, post ischemia insult analgesia will be given. Analgesia will be given post dose administration. In addition to the preoperative
administration of Butorphenol (0.2 mg/kg,IM), a 3 day post surgery regimen of Buprenorphine @0.02 mg/kg BID SC will be given. In some cases additional doses may be needed at the discretion of the facility veterinarian. 

  
 D-2. Route and Rationale of Test Article Administration: 

 
 The route of administration of the FGF-l will be by two direct injections
into the cardio-ventricular wall; one injection will be administered in 0.25 ml of a heparin/saline solution in the general area of the heart that has suffered an ischemic injury. The second injection of 0.25 ml will be in healthy heart tissue. The
site of both injections will be marked with a suture. This route of administration was selected because the test article is intended to be injected directly into the heart of human patients in order to stimulate new blood vessel formation.

			
	 DaVinci Biomedical Research ProdTM
	  	 
	Cardiotoxicity Study of Fibroblast Growth Factor (FGF-1) in Dogs	  	July 13, 2001
	 Study Number: DB-19
	  	Page 7 of l1

  
 F. Follow-up Dose
Administration: 
  
 Approximately seven days
after ischemic insult, the animal will be Anesthetized in accordance to section 6. C, and either femoral site, and left lateral rib cage will be clipped and prepped for aseptic surgery. Upon surgical preparation and aseptic draping of the animal, an
introducer and guide catheter will be placed as in the initial surgery, a angiogram will be taken of the circumflex artery. Upon completion of the angiogram a thoracotomy will be made between the 4-5 intercostal space to expose the pericardium
(prior to thoracotomy bupivacaine will be administered IM intercostal at a dose of 2mg/kg). The pericardium will be incised and 2-0 suture will be used to harness and elevate heart. The area of insult will be located and the test article or vehicle
dose will be administered by needle puncture into the myocardium. A thoracic catheter will be placed and the intercostal space will be closed with 2-0 non absorbable suture. The catheter will be exteriorized from a separate intercostal space to the
subcutaneous space and the air from the thoracic cavity will be removed using a 60cc syringe. Upon removal of all air the catheter will be removed and the exit site will be closed. 
  
 G. Post operative Observations: Post surgery the animal will be observed once daily for 3-5 days for any
‘abnormalities. The animal will be observed for any abnormalities in: skin, hair, respiratory, lethargy, fecal output, food consumption, dehiscence of surgical sites, edema, infection, and vocalization. All observations will be documented in
the study file. If abnormal observations are evident the study director or the attending veterinarian will be notified immediately. 
  
 H. Animals Found Dead or Moribund: Any animals found with life threatening signs which would indicate that they would not survive until the
next observation day will be immediately reported to the study director or the attending veterinarian. The time of death if applicable will be documented appropriately, and a full necropsy will be performed to evaluate the cause of death.

  

	7.	Animal Observations: 

  

	 	1)	Cageside observations: Cageside observations will be performed twice daily for mortality and moribundity. 

  

	 	2)	Monitoring Procedures: 

  
 a). Electrocardiogram: Electrocardiogram (ECG) tracings (lead II) will be obtained using the Datascope Passport II. 
  
 b). Direct Blood Pressure and Heart Rate: Heart
rate, and direct blood pressure parameters for MAP, SAP, and DAP will be monitored on day -7 pre and post ischemia formation on day 0 pre and post treatment, and at necropsy pre euthanasia. 

			
	 DaVinci Biomedical Research ProdTM
	  	 
	Cardiotoxicity Study of Fibroblast Growth Factor (FGF-1) in Dogs	  	July 13, 2001
	 Study Number: DB-19
	  	Page 8 of 11

  
 A. Euthanasia:
If animals are to be euthanized at the conclusion of the project the animals will be injected with sodium pentobarbital to cause euthanasia, which will be performed in accordance to the American Veterinary Medical Association (AVMA) Panel of
Euthanasia, and Journal of the American Veterinary Medical Association, 218 (5): 668-696, 2001. 
  

	 	11.	PROTOCOL CHANGES: If necessary to change an approved study protocol, changes must be made in writing between the study director and the sponsor. The changes and the
justification for the changes must be included in the section which will be replaced, and the new application must be approved by the study director and the sponsor, of which both parties must sign and date. The amendment will be attached to the
protocol. 

  

	 	12.	STUDY DEVIATIONS: In the case which a deviation from the protocol, and Standard Operating Procedure occurs, the reason for the deviation, the action taken, and the impact on
the study(if any) will be reported by the study director to the sponsor as soon as possible(if a significant impact is evident). 

  
 SPONSOR INFORMATION REQUIRED 
  
 SHIPPING: 
  

									
	 Sample Shipping Information

	 Type of Sample

	 	When

	 	Conditions-1

	 	Method

	 	Advance Notification-2 Y/N

	 Blood samples
	 	TBD	 	dry ice	 	o/n	 	y

  
 -1Specify condition of shipping, dry
ice, wet ice, cold packs, ambient temperature etc. 
 -1Specify courier©, overnight service (o/n), or standard (std) 
  
 -2Notification of person to receive package specified below. 

			
	 DaVinci Biomedical Research ProdTM
	  	 
	Cardiotoxicity Study of Fibroblast Growth Factor (FGF-1) in Dogs	  	July 13, 2001
	 Study Number: DB-19
	  	Page 9 of 11

  
 Samples shipped to: 

 

			
	Name:	 	Jack Jacobs, Ph.D.
		
	Company:	 	Phage Biotechnology Corp
		
	Address:	 	14272 Franklin Ave
		
	 	 	Suite 110
		
	 	 	Tustin, CA 92780
		
	Phone:	 	714-368-1520
		
	Fax:	 	714-368-1517

  
 Records Maintained: 

 
 Facility Records: 
  
 Animal room temperature and humidity 
 Water Analysis 
 Feed identification
and usage  
 In-Vivo Phases: 
  
 Animal receipt and disposition 
 Quarantine Data 
 Animal
Randomization 
 Fasting 
 Body Weights 
 Surgical Procedures 
 Treatment 
 Animal Observation 
 Monitoring Procedures 
 Sample
collection 
  
 Clinical Pathology: 
  
 Clinical Pathology Data 
  
 Pathology Records: 
  
 Pathology data 

			
	 DaVinci Biomedical Research ProdTM
	  	 
	Cardiotoxicity Study of Fibroblast Growth Factor (FGF-1) in Dogs	  	July 13, 2001
	 Study Number: DB-19
	  	Page 10 of 11

  
 PROTOCOL APPROVAL

  
 Cardiotoxicity Study of Fibroblast Growth Factor (FGF-1)
in Dogs 
  
 DaVinci Protocol Number: DB-19 
  

			
	 Sponsor:
	 	 Cardio Vascular Genetic Engineering / Phage Biotechnology Corp

	 	 	 14272 Franklin Ave Suite 110

	 	 	 Tustin CA 92780

  

					
	 /s/    JACK JACOBS

	  	 	 	  

	 Signature
	  	 	 	Date
			
	 Sponsor Representative
	  	 Jack Jacobs, Ph.D.
	 	 
			
	 Facility Performing
 Project:
	  	 DaVinci Biomedical Research ProdTM
 40 Maple Ave
 So. Lancaster, MA 01561
	 	 
	 /s/    MARIO PIO VILLANI

	  	 	 	  

	 Signature
 Mario Pio Villani
 Study Director
	  	 	 	Date

  

  

			
	 DaVinci Biomedical Research ProdTM
	  	 
	Cardiotoxicity Study of Fibroblast Growth Factor (FGF-1) in Dogs	  	July 13, 2001
	 Study Number: DB-19
	  	Page 11 of 11

  
 COMMITTEE REVIEW: 

 

			
	CHAIRMAN:_____________________________________________	 	TODAY’S DATE:_________________
		
	VETERINARIAN:_________________________________________	 	TODAY’S DATE:_________________
		
	 THIRD COMMITTEE
 MEMBER:_______________________________________________
	 	TODAY’S DATE:_________________
		
	 FOURTH COMMITTEE
 MEMBER:_______________________________________________
	 	TODAY’S DATE:_________________Agreement, dated June 23, 2004, between Catheter & Disposable Technology Inc.

 Exhibit 10.11 
  
 Catheter and Disposables 
 Technology Inc., 
 A division of CardioTech International 
  
 13845 Industrial Park Blvd., Plymouth, MN 55441 
 Phone: 763-557-1024 Fax: 763-557-0920 
  

			
	Date:	  	6/23/04
	Quotation:	  	#724 Rev. 2
		
	To:	  	Jack Jacobs
	Company:	  	CardioVascular BioTherapeutics 14272 Franklin Avenue #110 Tustin, CA 92780
		
	Telephone:	  	714-368-1520
	Fax:	  	714-368-1517

  
 Introduction: 
  
 Catheter and Disposables Technology, Inc. (CDT) a division of CardioTech International, is a
full-service medical device product development and manufacturing company focusing on catheters and medical disposable products based on molded and extruded components. CDT has assembled an industry-recognized team of technical experts with the
experience, expertise, and tools to develop and manufacture your products. 
  
 CDT
offers you turnkey solutions for your disposable product needs from idea generation and product specification to clinical prototyping, development, qualification testing, manufacturing, sterilization, and shipment of packaged product. 
  
 CDT is a FDA registered medical device manufacturer, ISO 9001, ISO 13485 and EN46001
certified, with a proven history of creating successful products that solve technical, time-to-market, quality, and regulatory compliance issues in a wide range of medical specialties. 
  
 As a partner with CDT, you gain a team of experts with experience providing products for many medical specialties. We’ve forged
relationships with many successful medical device companies both small and large. At CDT, we understand the products you want and can employ the processes you need to he successful. 
  
 Project Scope: 
  
 CardioVascular BioTherapeutics has an idea concept for a new non-invasive targeted drug delivery catheter for the cardiovascular market. CDT conducted a workshop yielding
4 specific designs of potential drug delivery catheters. From the workshop presentation, CardioVascular BioTherapeutics has selected two of the designs to be fabricated as first iteration prototypes. Specifically, CardioVascular BioTherapeutics is
requesting CDT to design, develop and fabricate prototypes for the “Drug Delivery Catheter w/Braided Anchor” and “Drug Delivery Catheter w/o Anchoring System” designs. 
  
 The project initiation will be as follows: 
  

	1.	CDT will work concurrently with CardioVascular BioTherapeutics to finalize the catheters designs. 

  

	2.	CDT will work concurrently with CardioVascular BioTherapeutics to create individual component engineering drawings. 

  

	3.	CDT will procure the following tooling and materials; 

  

	 	•	Proximal Shaft: One 3-Lumen, 8F PU extrusion (higher durometer) 

	 	•	Distal Shall: One 3-Lumen, 8F PU extrusion (lower durometer) 

	 	•	Fusing Dies and Fusing Jaws 

	 	•	Distal Marker Bands 

	 	•	Inner Shaft: One Single Lumen Extrusion 

  

 Page 1 of 8 

	 	•	50 27 Gauge Needles 

	 	•	20 Braided Stents 

	 	•	Mold for over-molding: inner Shaft/Needle/Braided Stunt 

	 	•	Deflection Wires 

	 	•	Assembly Mandrels 

	 	•	Machined handle components 

  

	4.	CDT will develop preliminary processes to fabricate the catheters. 

  

	5.	CDT will ship a minimum of 3 of each catheter design (6 total) to CardioVascular BioTherapeutics for evaluation. 

  

	6.	CardioVascular BioTherapeutics will provide feedback to CDT. 

  

	7.	Based on results of the first iteration of prototypes, CardioVascular BioTherapeutics will either request changes to the mutually agreed to design using the same materials and/or
with making minor modification to the tooling and CDT will fabricate a minimum of 3 additional of each catheter design (6 total) for a second iteration of prototypes. AND/OR 

  

	8.	CDT will deliver a minimum of 10 of one of the two designs based on the approval by to CardioVascular BioTherapeutics. 

  
 Key Assumptions: 
  

	•	The catheters will fall under CDT’s Phase 0 design controls. 

  

	•	The catheters are considered to be non-qualified and are not acceptable for human use or regulatory submission. 

  

	•	This quotation was formulated using a non-braided reinforced extrusion for the catheter shaft. 

  

	•	Given the current conceptual design, the prototype iterations may very slightly from the workshop drawings as unique specifications are defined. 

  

	•	CDT will perform functional integrity testing to ensure non-statistical reliability. 

  

	•	CardioVascular BioTherapeutics owns any tooling, molds and/or materials purchased per this contract. CDT will ship any remaining inventory of materials purchased by CardioVascular
BioTherapeutics provided there are no outstanding account receivables. 

  

	•	In the event of cancellation, CardioVascular BioTherapeutics shall be obligated to pay CDT for services performed, or for any outstanding periodic payments due and the cost of
materials, which CDT has committed, to purchase that cannot be cancelled or cancelled without penalty. The deposit set forth in this contract shall be first used to satisfy these amounts with any balance returned to CardioVascular BioTherapeutics.

  

	•	If CardioVascular BioTherapeutics provides CDT with its shipping carrier’s account number and preferred method of shipment, CDT will not hill CardioVascular BioTherapeutics for
shipping and CDT’s standard 15% handling charge. 

  

	•	CardioVascular BioTherapeutics will be open to negotiating mutually agreeable materials and design selections. 

  

	•	CardioVascular BioTherapeutics will respond to CDT in a timely manner to prevent any delays in the project schedule, 

  

	•	CDT will ship the product bulk non-sterile. 

  

	•	CDT understands that Jack Jacobs will act as a point of contact for project questions and information delivery. 

  

 Page 2 of 8 

 Deliverables: 
  

	•	CDT will provide CardioVascular BioTherapeutics with minimum of 3 of the “w/Braided Anchor” design for the first iteration. 

  

	•	CDT will provide CardioVascular BioTherapeutics with minimum of 3 of the “w/o Anchoring System” for the first iteration 

  

	•	CDT will provide CardioVascular BioTherapeutics with minimum of 3 of the “w/Braided Anchor” design for the second iteration (if necessary). 

  

	•	CDT will provide CardioVascular BioTherapeutics with minimum of 3 of “w/o Anchoring System” design for the second iteration (if necessary). 

  

	•	CDT will provide CardioVascular BioTherapeutics with minimum of 10 of one of the two designs (“w/Braided Anchor” or “w/o Anchoring System”) for the final
iteration. 

  
 Price: 
  
 CDT estimates that it will be $69,613 for labor and expenses to complete Steps 1 through 8
as outlined in the Project Scope. 
  

								
	 Engineering Fees:
	  	 	 	 	 	$	37,500
			
	 Expenses: Proximal Shaft: One 3-Lumen, 8F PU extrusion
	  	$	2,500	 	 	 	 
	 Distal Shaft: One 3-Lumen, 8F PU extrusion
	  	$	2,500	 	 	 	 
	 Fusing Dies
	  	$	250	 	 	 	 
	 Fusing Jaws
	  	$	175	 	 	 	 
	 Distal Marker Bands
	  	$	150	 	 	 	 
	 Inner Shaft; One Single Lumen Extrusion
	  	$	1,100	 	 	 	 
	 27 Gauge Needles (50 units)
	  	$	400	 	 	 	 
	 Braided Supports (20 units)
	  	$	7,350	 (estimated)	 	 	 
	 Mold (Over-molding inner Shaft/Needle/Braided Stent)
	  	$	900	 	 	 	 
	 Deflection Wires
	  	$	325	 	 	 	 
	 Assembly Mandrels
	  	$	275	 	 	 	 
	 Handle components
	  	$	12,000	 (30 units x $400)	 	 	 
			
	 Total expenses
	  	$	27,925	 	 	 	 
	 Plus 15% handling
	  	 	 	 	 	$	32,113
	 	  	 	 	 	 	
	

	 Total Project Price
	  	 	 	 	 	$	69,613

  
 Delivery: 
  
 CDT will commence the project within three days after receiving a purchase order and
deposit. CDT is forecasting to ship the first iteration prototypes in 12 to 14 weeks. 
  
 Billing Terns: 
  
 A purchase order for $69,613 and a deposit of
$20,000 is required to initiate this project. Billing will be invoiced monthly, at current billing rates, for work performed. CDT will itemize labor and expenses monthly. Expenses, billed at cost plus 15%, are invoiced monthly and include, but are
not limited to materials, extrusions, tooling, fixtures and molds. Expenses and labor will not exceed $69,613 without prior customer approval. The actual amount may be higher or lower than the estimate. If the work requires funding in excess of
$69,613 additional funding will be requested. The deposit will be applied to the last invoice(s). In the event, after all invoices have been applied to the customer deposit, a remaining deposit amount exists, CDT will return the amount due, provided
all outstanding invoices have been paid in full. Standard Terms and Conditions enclosed. 
  
 This quote is valid for 60 days. 
  

 Page 3 of 8 

 Agreement: 
  
 IN WITNESS WHEREOF, the parties have caused this Agreement to be executed as of the initiation of the purchase order: 
  

					
	 CATHETER AND DISPOSABLES TECHNOLOGY, INC.
	 	 	 	 CARDIOVASCULAR BIOTHERAPEUTICS

			
	 /s/    Laim M. Johnson        
	 	 	 	 /s/    Jack Jacobs        

	 Signed
	 	 	 	 Signed

			
	 Liam M. Johnson
	 	 	 	 Jack Jacobs

	 Print Name
	 	 	 	 Print Name

			
	 General Manager
	 	 	 	 VP & COO

	 Title
	 	 	 	 Title

			
	 6/23/04
	 	 	 	 7/13/04

	 Date
	 	 	 	 Date

  

 Page 4 of 8 

 CDT Terms and Conditions, D & D and Mfg 
  
 This agreement shall apply to all work and projects performed by Catheter and Disposables
Technology, Inc., a Minnesota corporation having an address at 13845 Industrial Perk Blvd Plymouth, Minnesota 55441 (hereinafter called CDT), for Its Clients (hereinafter called CLIENT). 
  
 I.    GENERAL TERMS 
  
 A.    Project, definition statement, purchase orders or contracts shall define the work to be performed on a best effort basis by CDT. This agreement
outlines the terms that apply regarding tacit work. In the absence of a separate written contractual agreement specifically amending or intended to substitute for this agreement the terms outlined in this agreement shall apply. In the event of terms
that are not specifically defined in amending or substituting agreements, the term in this agreement shall govern. 
  
 B.    Initial payment of fees which may be made in advance of work being performed are nonrefundable. Advances against expenses in which CDT has not
made commitments or purchase orders or otherwise are unused will be refunded within sixty (60) days. 
  
 CI.    Projects with payment schedules based upon achievement of project milestones may be allowed at the request of the CLIENT. However, CLIENT will be responsible for all balance of the direct
expenses and fees specified in the payment schedule. 
  
 CII.    Projects with payment schedules based upon application of CDT’s personnel resources may be slowed or terminated at the request of the CLIENT. However, a thirty (30) day notice will be required foe a twenty
five (25%) reduction in CDT resources, sixty (60) days for flay percent (50%) reduction, and ninety (90) days for reductions greater than seventy five (75%) percent. For the purposes of the above calculations R&D and manufacturing resources will
be calculated as separate categories using current billing rates. 
  
 DI.    Projects with payment schedules based upon application of project milestones may have changes made, for example, in materials, product design, manufacturing processes or product specification at the written
request of the CLIENT. However, such changes must be approved in writing by CDT and the fees specified in the payment schedule and/or product cost will be adjusted to reflect the changes. 
  
 DII.    Projects with payment schedules based upon application of CDT’s personnel resources may have changes made,
for example, to materials, product design, manufacturing processes or product specification at the written request of the CLIENT. However, such changes must be approved in writing by CDT and the impact of such changes upon project schedules and/or
product costs are the responsibility of the Client. 
  
 E.    The client can issue a stop work order for any PO with a five (5) day written notice. However, in the event of cancellation, the client shall be obligated to pay CDT for services performed, services related to the
cancellation or for any outstanding periodic payment due and the cost of materials and/or direct expenses which CDT has committed to purchase that cannot be cancelled or cancelled without penalty. 
  
 F.    Payments are due within thirty (30) days of the date of invoice.
Labor will be billed at CDT’s current billing rates and expenses (e.g. shipping, sterilization, biocompatibility, tooling supplies, and materials shall be billed at CDT’S cost plus fifteen percent (15%). Unless otherwise specified or
required by law, at prices will be quoted end billed exclusive of taxes or duties. Such taxes, where applicable, will appear as additional terms on invoices. 
  
 G.    Design and documentation will be controlled by CDT standard systems. Client responsibility will be for items indicated in IVD, IVI, IVL and IVJ,
shelf life determination, and product design validation (unless otherwise defined in writing). 
  
 II.    TERMINATION 
  
 A.    In the event CLIENT terminates work between CLIENT and CDT, sixty (60) days written notice is required and terms in 1B, IC, IE and/or IVB shall apply. 
  
 B.    In the event CLIENT desires that CDT assist in transferring development or manufacturing to an alternate site,
CLIENT shall request a quote from CDT to affect such a transfer. Each party shall remain the exclusive owner of its proprietary information, including without limitation all trade secrets, patents, purchasing specifications, 
  

 Page 5 of 8 

 manufacturing processes, quality systems and/or internal practical and such proprietary information shall be valued and
protected as such. CDT acknowledges that the CLIENT will own all rights to the Intellectual Property resulting directly from the Research Work. CDT will retain all right to CDT Technology. 
  
 “CDT Technology” shall mean techniques, trade secrets. methods,
processes, quality systems, and confidential know how possessed by CDT prior to its commencement of, generated outside the scope of its work under this Agreement, generated inside the scope of work without compensation from the CLIENT or any process
related know-how used as part of the “work for hire”, and shall include improvements to CDT Technology generated during the scope of its work under this Agreement. 
  
 “Intellectual Property” shall mean any and all works of authorship, inventions, copyrights, patent applications
and patents (including inventor’s certificates, design applications end utility models) throughout the world, including any substitutions. extensions, reissues, reexaminations, renewals. divisions, provisionals, continuations and
continuation-in-part of the foregoing which relate to the research work. 
  
 “Compensation” shall mean payment in addition to labor fees and direct expenses as set forth in a specific quote. 
  
 In addition, CLIENT shall have a non-exclusive royalty-free license for all rights belonging to CDT, yet not assigned to the CLIENT under this Agreement
in connection with the Project. Such license will be sub-licensable by CLIENT. 
  
 C.    CDT is under no obligation to disclose CDT proprietary information without compensation,. unless such disclosure is inherently required for CDT to perform obligations hereunder or under any other agreement between
CLIENT and CDT. 
  
 D.    CDT is under no obligation to
disclose any documents contained in the Device Master Record without compensation. 
  
 III    MISCELLANEOUS 
  
 A.    Independent Contractor. It is agreed that CDT will furnish services for an independent contractor and not as an employee of CLIENT. 
  
 B,    Indemnity. CLIENT shall indemnify and hold CDT harmless from any loss, damage or cost (including but not limited
to reasonable attorney’s fees and expenses) arising from any claim that product or its operation infringes a patent, trademark, copyright or proprietary right or any claim regarding use of product supplied by CDT which results from any reason
other than a failure of CDT to meet the requirements defined in IVE. 
  
 C.    CDT guarantees good workmanship in accordance with generally accepted professional standard for work of this nature, CDT MAKES NO OTHER GUARANTEES OR WARRANTIES, EXPRESS OR. IMPLIED, INCLUDING ANY IMPLIED WARRANTY
OF MERCHANTABILITY OR FITNESS FOR A PARTICULAR PURPOSE. IN NO WENT WILL EITHER PARTY BE LIABLE FOR ANY LOST PROFITS OR INCIDENTAL OR CONSEQUENTIAL DAMAGES REGARDLESS OF WHETHER ADVISED OF THE POSSIBILITY OF SUCH DAMAGES, NOR ANY CLAIM AGAINST SUCH
PARTY BY ANY OTHER PARTY. CDT’s maximum liability arising out of its performance under this Agreement, whether in contract or in tort, is limited to the lesser of Five Hundred Thousand Dollars ($500,000) of any money paid to CDT by Client under
this Agreement. 
  
 D.    Governing Law. This document shall
be construed and interpreted under and in accordance with the laws of the State of Minnesota, USA. 
  
 E.    Arbitration. Any disputes arising out of this agreement shall be resolved by binding arbitration under the rules of the American Arbitration Association and shall take place in Minneapolis,
Minnesota or Now York, New York. Such disputes shall be submitted to arbitration within ten (10) days of written notification of the existence of a dispute. 
  
 F.    All notices. requests or other communications required or permitted to be given under this Agreement will be in writing and will be delivered by
express courier, such as Federal Express, or sent by certified or registered mail, postage and certification prepaid, to CLIENT or CDT. Any notice given as aforesaid will be deemed given and
effective            ,on actual delivery. Any Party may change its address for notice by notice given in accordance herewith. 
  

 Page 6 of 8 

 The fallowing terms and condition are particularly applicable to long term product supply and the supply of product for
human use. 
  
 IV.    SUPPLY OF PRODUCT 
  
 A.    If and when CLIENT places orders for CDT to manufacture production
units, the price to CLIENT shall be based upon actual material, expenses (e.g. sterilization, bioburdens). labor and overhead cost, plus a forty percent (40%) gross margin, 
  
 B.    CDT shall plan according to a production schedule supply by CLIENT. Actual production shall be in response to
issued purchase orders. Parts purchased by CDT in accordance with the production schedule in excess of actual orders (or made obsolete bye CLIENT initiated change) shall be purchased by CLIENT at CDT’s cost (including 13 percent (13%) burden).

  
 C.    CDT shall test product for conformance to
specifications prior to shipment. CLIENT is responsible for evaluating all product, and if any product ii claimed to be defective by CLIENT or a customer of CLIENT, shall obtain a Return Authorization from CDT. In any event product shall be deemed
accepted ten days after delivery to CLIENT. If CDT, after inspection of each product, verifies that such condition has not been caused by misuse, abuse, repair, alternation, accident or negligence in storage, transportation or handling, CDT’s
liability shall be limited to repair of defects in materials or workmanship, or replacement of the returned product. Such returns must occur within forty-five (45) days of delivery of product. After forty-five (45) days, product will be considered
accepted and non-returnable. 
  
 D.    CLIENT is responsible
for the labeling (including shelf-life specifications), use end shipment (including export) of the product and is responsible for meeting all applicable FDA and other regulations. 
  
 E.    CLIENT is responsible for sterilization validation and sterilization unless contracted by CUT. 
  
 F.    CLIENT is responsible for packaging validation unless contracted by
CDT. 
  
 G.    CLIENT is responsible for biocompatibility
testing unless contracted by CDT. 
  
 H.    CDT will
manufacture, package, label, store and ship the product using processes and techniques as defined, accepted or agreed to by CLIENT and CDT. Acceptance of product constitutes acceptance of the process and techniques used for their manufacture These
processes and techniques will be consistent with all applicable GMP and FDA requirements for product and usage as defined by CLIENT and accepted or agreed by CDT. 
  
 I.    All shipments are F.O.B. point of shipment, transportation at CLIENTS expense, with risk of loss passing to CLIENT
at point of shipment. 
  
 J.    CDT reserves the right to
deliver products in installments and to over or under ship by ten percent (10%). Partial shipments will be invoiced as shipped. 
  
 K.    CLIENT is responsible for labeling, use, safety and efficacy. per appropriate regulations of all human use of devices supplied by CDT under
development supply phases of projects. All labeling will be defined or supplied by CLIENT. 
  
 L.    CLIENT may request changes to specifications, labeling, materials or any ether aspect of a manufacturing productions units being supplied by CDT, however, CLIENT will be responsible the all
costs associated with such changes. When CLIENT requests a change CDT will estimate the price of the change and will receive CLIENT approval before implementing the change. CLIENT will be responsible for the price of obsolete inventory per IVB.

  
 M.    CDT and CLIENT shall not make changes to jointly
controlled documents (i.e. CDT # XXXXX-5XX) without prior written approval of the other party. 
  
 N.    The CLIENT is responsible for all payment of invalid product manufactured by CDT or a third party provided the CLIENT failed to include the current revision level for the products, IFU and
label on the purchase order. 
  

 Page 7 of 8 

 V.    REGULATORY REPORTING 
  
 CLIENT is responsible for meeting all applicable FDA and other regulations. CDT is responsible for meeting GMP, FDA and
other regulations, which apply to a supplier of product to the specification of another entity. FDA MDR regulations mandate responsibilities which can place requirements upon CDT. Therefore: 
  
 A.    CLIENT is responsible for product listing and meeting all other
applicable reporting requirements. CDT is responsible for maintaining establishment resignation. 
  
 B.    CLIENT shall forward to CDT any complaints it wishes CDT’s assistance in investigating. CLIENT is responsible for providing CDT with product and/or pertinent information such as lot
number of the product involved. 
  
 C.    CDT shall be
responsible for supporting CLIENT’s investigation or complaints by promptly conducting analysis and testing of the product involved and shall report promptly to CLIENT subsequent to such analysis and testing. Expenses associated with such
investigations will be the responsibility of the CLIENT unless otherwise agreed to by CDT. 
  
 D.    CLIENT shall provide CDT with copies of all reports made pursuant to MDR regulations. This is particularly applicable when a report is required by MDR regulations as CDT may be required to
submit a report if not informed that it has been submitted by CLIENT. 
  
 E.    Both parties stall designate an individual within their morn-nation to be the primary contact regarding regulatory issues. 
  
 F.    Device History Record and Design History Records will be stored by CDT for a minimum of five (5) years from the data written or issues.
Technical file is the responsibility of the CLIENT. 
  

 Page 8 of 8

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