BIOE2010 Exam 3

Why do patents matter?

"If you don't have a patent, you don't have anything"

What are considered intellectual property?

Trademarks, copyrights, trade secrets and patents.

What is a Trademark?

A trademark is any word, name, symbol, or device or any combination thereof adopted and used to identify goods and distinguish them from those manufactured and sold by others.

i.e. Google, Apple

What is a Copyright?

A Copyright is an exclusive legal right to print, publish, perform, film, or record material.

What is a Trade Secret?

Secret device or technique used especially in a trade. If effective, can last forever.

i.e. Gore's teftlon

What is a patent?

A patent is a claim(s) of invention.

It permits its owner to exclude others from making, using, or selling an invention.

How long do patents last?

20 years from filing.

What types of patents are there?

Utility patent, Design patent, Plant patent, Provisional patent.

What is a Utility Patent?

a utility patent is obtained for processes (chemical, mechanical, or electrical procedures), machines, articles
of manufacturing, and compositions of matter.

What is a Design Patent

obtained for an invention
of a new, original and ornamental design for an article of manufacture. Design patent protection extends only to an item's appearance, not its functional aspects

What is a Plant patent?

granted for a distinct and new variety of a cultivated asexually reproduced plant.

Owning the genetics of the plant

What is a provisional patent?

contains a
specification sufficient detail to allow one skilled in the art to practice the invention. A provisional is a preliminary action to provide the inventor 12 months to develop the full patent claims.

"Officially on record"

What are the requirements of an invention to be patented?

1. It must fall into a statutory class
2. Must be useful
3. Must be novel
4. Must be NOT OBVIOUS TO A PERSON WITH ORDINARY SKILL IN THE ART to which the subject matter pertains.

- Colleague doesn't find it "obvious"

What are the statutory classes an invention must fall into?

Processes, machines, manufactures, and compositions of matter (primarily biomaterials which are strong & defensible)

What is an Independent Claim?

A standalone claim that contains all the limitations necessary to define an invention.

What is a Dependent Claim?

Must refer to a claim previously set forth and must further limit that claim.

"Dependent on a precedent"

Who can file a patent application?

US patent applications must be filed in the name of the inventor(s). However, patents can be assigned to others.

Who is the assignee?

the legal owner of a patent (unless you're an entrepreneur, usually your employer.

i.e. Kevin Webb --> Inventor
Clemson University --> Assignee

Who is an inventor?

An inventor must make creative contributions to the invention.

If you only run the experiment, you're NOT the inventor.

If you want to patent you NEED TO:

Maintain a notebook, make progress on completing the invention, and seek professional assistance.

If you have something you want to patent, DON'T:

DO NOT publish an article,
sell/offer anything based upon the invention or accept a purchase order, explain your invention to anyone without a confidentiality agreement.

What is a non-disclosure agreement?

A signed agreement that states you will not disclose company trade secrets

What is 'first to file'?

The first to file a patent will receive the patent. Consistent with international practice.

What is the value?

How you utilize your patent protection.
- Exclusion of others
- Give your business exclusivity
- Licensing rights to others for consideration

What is a license?

legal document granting rights to intellectual property and/or material in exchange for good and valuable consideration.

What are the rights to the invention?

Type of license (exclusive, non-exclusive, research only), field of use (i.e. cardiovascular/orthopedics), a period of time, a territory (USA vs. Europe)

What goes into a license?

A royalty or a grant of the right to prohibit others from practicing the technology.

How does IP impact me?

- Researcher in a large company (Named as inventor but all rights assigned to company as a condition of employment)
- Product manager/marketing (May work w/ all types of IP in marketing of a product)
- Entrepreneur (Excludes others, creates value, can be costly to protect)

Goals of Wound Closure

- Accelerate healing and reduce scarring
- Reduce the opportunity for infection
- Restore mechanical strength to wounded tissue during healing
- Reduce blood loss-hemostasis
- Minimize the formation of adhesions- internal wound closure

What is debridement?

- Remove foreign material
- Create sharp wound edges
- Can accelerate healing and improve cosmetic outcome

What are some suture applications?

- Closure of surgical incisions (dermal/internal)
- Securing medical devices to patient tissue (permanent implant)
- Re-connection of tissues separated by injury (permanent implant)
i.e. tendon & peripheral nerve

What are types of ABSORBABLE suture material?

Typically used for wounds (2-3 months)
- Catgut (isolated from sheep or bovine intestine)-commonly treated with chromium trioxide-reduces absorption rate 40 to 75 days, reduces tissue reaction
- Polyglycolic acid (PGA) and poly lactic-co- glycolic acid (PLGA)

What are types of NON-ABSORBABLE suture material?

Implants and Wounds
- Cotton, silk, PET, polypropylene

What are the products of PLGA degradation?

hydrolysis results in a hydroxyl & carboxylic acid group from an ester bond.

What is a hydrogel? What are some solubility properties?

- Cross-linked network of water soluble polymers
- Once cross-linked MW essentially goes to infinity
- Due to cross-linking the hydrogel is insoluble, but holds large amounts of water (up to 95% water content) due to hydrophilic nature of polymer chains

i.e. Jello

Why should we use hydrogels?

- Human body is 70% water
- High water content of hydrogels provide mechanical properties similar to soft tissue
- Primary applications include contact lenses, intraocular lens, tissue sealants, tissue engineering

How are hydrogels created?

Crosslinking mechanisms (Physical, ionic, covalent)

- 'Click' chemistry where there are NO byproducts and high efficacy

What is an adhesive?

A substance capable of holding materials together in a functional manner

What is a sealant?

A material applied to a joint in paste or liquid form that hardens or cures in place, forming a barrier against gas or liquid entry-particularly blood leakage

What are surgical adhesives/sealants used for?

- Rapid wound closure
- Improved prevention of blood loss
- Minimizing deformation of tissue (reduce scarring)
- Closure of mechanically weak tissues that are difficult to suture (liver, kidney, spleen)

What is in situ forming

liquid to solid transformation occurs during application (in situ polymerization of liquid monomers)

*STABILITY*

What is cure time?

how long liquid-solid transformation requires

*

What is shelf life?

how long can it be stably stored as a monomer without premature polymerization

How do we test tissue bond strength?

Shear (Pa) = Maximum Load (N)/bonded area (m^2)

Where does adhesive failure occur?

At the tissue/material interface

Where does cohesive failure occur?

Within the substance of the adhesive

Where does substrate failure occur?

Failure of the tissue substrate

What is an example of an adhesive?

Cyanoacrylate

What is an example of a sealant?

Fibrin glue, BioGlue, ProGel, DuraSeal, FocalSeal

What are some properties of cyanoacrylates?

Composed of a cyano and acrylate groups. Approved for topical use in humans.

Degradation is __ proportional to length of alkyl chain

Directly, longer = slower

How are cyanoacrylates activated?

Activated by water & amine groups present on proteins in tissue.

The tissue initiates polymerization therefore it is chemically bonded to the adhesive, providing exceptional bond strength.

How do you use cyanoacrylate adhesives?

Use proper, good wound care practices. Appose wound edges tightly. DO NOT get adhesive in the wound.

What is the fate of cyanoacrylate?

It undergoes epithelial shedding aka delaminates

What is fibrin glue?

A biological adhesive and hemostatic agent

What is tisseel (Baxter)?

Mimics the coagulation cascade

What are the clinical considerations of sealants?

- Where the source of protein come from
- Possible disease transmission
- Minimize risk
- Purified proteins from batches of human blood
- Commercial products

What is BioGlue?

Composed of two solutions: bovine serum albumin (BSA) and glutaraldehyde (cross-linker)

What is the intended use of BioGlue?

Sealing suture lines in vascular implants. Originally aortic grafts, now many applications.

What is cross linking?

Step-growth polymerization between an amine & aldehyde which forms an imine group.

What is BSA?

Protein macromolecule that has multiple lysine residues, polar, located near the surface, with amine side groups.

What is the issue of BioGlue?

It cures too fast and glutaraldehyde is toxic.

How are BioGlues designed?

Typically with a double barrel syringe and a static mixer.

What is a double barrel syringe?

Allows two highly reactive solutions to be stored separately and stably in one device.

What is a static mixer?

Coiled piece of metal in the syringe tip which allows for mixing of the two solutions without agitation.

What is ProGel?

Replacing glutaraldehyde with a non-toxic PEG-based component which makes it bioinert & water-soluble.

What is DuraSeal?

Replace BSA with synthetic multi-functional amines. This renders it "xeno-free" and therefore, cannot cause zoonotic diseases.

What is xeno-free?

Does not contain any animal-derived products

What are zoonotic diseases?

Animal-borne diseases can become transmissible to humans.

What is Focal Seal?

Undergoes radical polymerization which is a photoinitiated process where light generates free radicals.

What is FocalSeal composed of?

Acrylate - Ester- PEG - Ester - Acrylate

Acrylates are the cross-linkers
Esters are degradable
PEG is water soluble & bioinert

What is the procedure for using FocalSeal?

1. Coat tissue with a solution of eosin-a dye which acts as a photoinitiator-compound that generates free radicals when exposed to light.
2. Apply viscous PEG precursor solution
3. Irradiate with light to cure.

What is the leading cause of death in the US?

Cardiovascular disease in age 65 or older.

The heart is a pump that uses what type of transport medium?

Blood

Almost every cell is within 100 micrometers of a capillary. How does transport occur?

Transport is via diffusion which is distance-limited.

For tissue engineering, the primary issue of recreating the circulatory system is

creating a microvasculature

Where is the systemic circuit and what does it do?

It's located on the left side of the heart.
Blood vessels carry the functional blood supply to and from all body tissues.

Where is the pulmonary circuit and what does it do?

Right side of the heart.
Blood vessels carry blood to and from lungs.

What are capillaries?

Microscopically small blood vessels between arteries and veins where oxygen diffuses to surrounding tissue. (All cells are within 100 uM of a capillary)
- smallest blood cells
- tunica intima
- exchange of materials between blood & interstitial fluid

What do red blood cells transport?

Hemoglobin

What is EPO and what does it do?

Epo is the first recombinant protein drug created by Amgen which stimulates red blood cell production.

Epo is __ responsive.

hypoxia

What does hemoglobin do?

Contains iron which reversibly binds to oxygen.

How do capillaries tie into the blood-oxygen transport?

When there are low levels of oxygen, oxygen will dissociate from hemoglobin and diffuse into surrounding tissue.

Can you label the structure of the heart?
(Components of heart wall & chambers)

What is the endocardium?

Inner surface of the myocardium.
Composed of endothelial cells which provide a "perfect" blood contacting surface that does not initiate coagulation.

What is the myocardium?

Myo - muscle
Composed of cardiomyocytes which control contraction and relaxation of the heart.

What is the epicardium?

Composed of fibroblasts & collagen which make up the outer surface of the myocardium.

What are cardiomyocytes

Cells responsible for generating contractile force in the intact heart.

*POST-MITOTIC*

Contain gap junctions which open channels between cells.
In turn, shares the cytoplasmic contents which lead to electric coupling.

What are the atriums?

- Receiving chambers
- Relatively small, thin-walled chambers
- Blood only pushed to ventricles

What are ventricles?

- Discharging chambers
- Make up most volume of the heart

What are the 4 chambers of the heart and where do they transport blood?

Right atrium (Blood from body)
Right ventricle (Blood to lungs via the pulmonary artery)
Left atrium (Blood from lungs via pulmonary vein)
Left ventricle (Blood from body via the aorta) (Walls 3X's as thick as right ventricle)

Diastole

Heart relaxed, filling with blood

Systole

Heart contracting, pumping blood

What is the cardiac cycle?

- Atrial diastole (Relaxed atrium allowing blood from body and lungs to fill atrium)
- As atria fill with blood, pressure rises in ventricles forcing tricuspid & mitral valves to open, allowing blood to fill diastole ventricles.
- Atria contracts (systole) filling ventricles to capacity.
- Pressure in atria and ventricles equalize and tricuspid & mitral valves close
- Ventricles contract (systole) causing ventricular pressure to rise and aortic and pulmonic valves open.

What is systolic pressure?

Maximum pressure achieved during ventricular contraction

What is diastolic pressure?

Lowest pressure that remains in the arteries before the next ventricular contraction

What do the heart valves do?

- Blood flow only occurs in one direction.
- Valves direct blood flow and prevent back flow.

What are the atrioventricular valves?

tricuspid and mitral valves

What are the semilunar valves?

pulmonary and aortic