This document provides an overview of biotechnology and recent patent law cases affecting patent eligibility of biotechnology inventions. It begins with primers on biotechnology topics like DNA, proteins, and therapeutic products. It then discusses why strong patent protection is essential for biotechnology given the lengthy and expensive research and development process. The document reviews various biotechnology patent claims and recent Supreme Court cases that have impacted patent eligibility of diagnostic methods, natural correlations, and processes applying natural relationships. It concludes with a discussion of personalized medicine and precision diagnostics representing future areas for biotechnology.

1. Biotechnology:
Technology, Role of Patents, and Patent
Eligibility under 35 U.S.C. § 101
University of Washington School of Law
Advanced Patent Law P545
Gary M. Myles, Ph.D.
February 1, 2012

2. Topics Covered
• A Biotechnology Primer
• Why is Strong Patent Protection Essential
to the Biotechnology Industry?
• Biotechnology Patent Claims
• Recent Cases Affecting Patent Eligibility
under 35 U.S.C. § 101

3. A Biotechnology Primer

4. The Eukaryotic Cell

5. DNA

6. The Central Dogma of Molecular Biology

7. RNA Splicing in Eukaryotic Cells

8. The Genetic Code

9. Amino Acids are the Building Blocks of Proteins

10. Proteins are Linear Polymers of Amino
Acids

11. Proteins adopt Three-dimensional
Structures

12. Therapeutic Biotech Products
• Nucleic Acid-based Therapeutics
– DNA-based Cancer Vaccines
– RNAi and antisense
– Viral Vectors for Gene Therapy
• Protein-based Therapeutics
– Cytokines and Soluble Receptors
– Vaccines against Infectious Disease
– Antibodies and other Immunotherapeutics

13. Why is Strong Patent Protection Essential
to the Biotechnology Industry?

14. Biotech Drug Discovery Process Timeline

15. Many Compounds Tested for Every
Product on the Market

16. Very Expensive and Time Consuming
to Get a Biotech Product on the
Market
• Average Cost to Develop a New
Biotechnology Product is $1.2
Billion, According to the Tufts Center for
the Study of Drug Development
(November 09, 2006)

17. Role of Patents
• Patents provide a limited monopoly such
that competitors are excluded from the
market for a limited period of time
• The limited monopoly afforded by
patent protection provides the incentive
for companies to invest in product R&D

18. Biotechnology Patent Claims

19. Biotechnology Patent Claims
• Product Claims
– A DNA (RNA, polynucleotide) comprising
the nucleotide sequence of SEQ ID NO: 1.
– A protein (peptide, polypeptide) comprising
the amino acid sequence of SEQ ID NO: 2.

20. Biotechnology Patent Claims
• Therapeutic Method Claims
– A method for the treatment of a
disease, said method comprising the step of
administering to a patient a composition
comprising a DNA
(RNA, polynucleotide, protein, peptide, poly
peptide) comprising the nucleotide (amino
acid) sequence of SEQ ID NO: 1.

21. Biotechnology Patent Claims
• Diagnostic Method Claims
– A method for the detection of a disease, said method
comprising the steps of:
• isolating from a patient sample a DNA that is homologous
to SEQ ID NO: 1,
• comparing the nucleotide sequence of said DNA to the
nucleotide sequence of SEQ ID NO: 1,
• determining whether said DNA comprises one or more
nucleotide substitutions as compared to SEQ ID NO: 1,
wherein the presence of a nucleotide substitution is
predictive of said disease.

22. 35 U.S.C. 101
Patentable Eligibility

23. 35 U.S.C. 101
Patentable Eligibility
Whoever invents or discovers any new and
useful
process, machine, manufacture, or
composition of matter, or any new and
useful improvement thereof, may obtain
a patent therefor, subject to the
conditions and requirements of this title

24. Patentable Subject Matter:
Fundamental Principles
• Funk Bros. v. Kalo (S.Ct. 1948)
– Mixed culture of root-nodule bacteria for
inoculating seeds of leguminous plants
• No patentable subject matter
– Each species infects same group of plants
– No species acquires a different use
– No change in the individual bacteria
– No change in their individual utilities
– Use in combination does not improve
natural functioning

25. Patentable Subject Matter:
Fundamental Principles
• Funk Bros. v. Kalo (S.Ct. 1948)
– “Manifestations of nature are free to all men and
reserved exclusively to none”
• Laws of nature
– E = mc2
– Law of gravity
• Physical phenomena
• Principles
• Abstract ideas
• Products of nature

26. Patentable Subject Matter:
Fundamental Principles
• Diamond v. Chakrabarty (S.Ct.
1980)
– Dr. Chakrabarty
• Created oil-eating bacterium
• Claimed “a bacterium from
the genus Pseudomonas
containing therein at least
two stable energy-
generating plasmids, each of
said plasmids providing a
separate hydrocarbon
degradative pathway.”

27. Patentable Subject Matter:
Fundamental Principles
• Diamond v. Chakrabarty (S.Ct. 1980), cont.
– USPTO
• Rejected claim because a bacterium is
– A “product of nature”
– A living thing
– Supreme Court
• Upholds validity of Chakrabarty’s claim
– “Anything under the sun that is made by
man”

28. Are These Inventions Patentable?
• “Biologically pure” bacterial culture
– Yes per CCPA in In re Bergy (1977)
– The culture is not a “product of nature” because the culture
did not exist in nature in its pure form
• “Purified and isolated” DNA sequences
– Yes per Fed. Cir. In Amgen v. Chugai (1991)
• “Purified and isolated” stem cells
– Yes per USPTO (Q. Todd Dickinson)
• Hydrostatically altered Pacific polyploid
oysters,
– Yes per Ex parte Allen (BPAI 1987)
• A transgenic non-human mammal
– Yes per Phil Leder, US Patent No. 4,736,866; “The Harvard
Mouse”

29. LabCorp v. Metabolite (S.Ct. 2006)
• Claim at issue
13. A method for detecting a deficiency of
cobalamin or folate in warm-blooded
animals comprising the steps of:
• assaying a body fluid for an elevated level of
total homocysteine; and
• correlating an elevated level of total
homocysteine in said body fluid with a
deficiency of cobalamin or folate

30. LabCorp v. Metabolite (S.Ct. 2006)
• Lower Courts
– Upheld the patent claim’s validity and found that
LabCorp infringed the claim
• Supreme Court
– Granted cert to determine whether claim is invalid
because it seeks to “claim a monopoly over a basic
scientific relationship”
• Correlation between in vivo cobalamin/folate levels and
in vivo homocysteine levels
– Dismissed writ of certiorari as improvidently
granted

31. LabCorp v. Metabolite (S.Ct. 2006)
• Justice Breyer dissent
– Laws of nature are unpatentable because
“sometimes too much patent protection can
impede rather than ‘promote the Progress of
Science and useful Arts.’ ” U.S. Const., Art 1, 8
• “the enormous potential for rent seeking that
would be created if property rights could be
obtained in [those basic principles]” and
• “the enormous transaction costs that would be
imposed on would-be users”

32. LabCorp v. Metabolite (S.Ct. 2006)
• Justice Breyer, cont.
– “There can be little doubt that the correlation
between homocysteine and vitamin deficiency set
forth in claim 13 is a ‘natural phenomenon’ ”
– “*t+he process described in claim 13 is not a process
for transforming blood or any other matter.
– Claim 13’s process instructs the user to
• (1) obtain test results and
• (2) think about them”

33. So, what makes a process
patentable?

34. In re Bilski (Fed. Cir. 2008)
Claim 1. A method for managing the
consumption risk costs of a commodity
sold by a commodity provider at a fixed
price comprising the steps of:
(a) initiating a series of transactions … ;
(b) identifying market participants … ;
and
(c) initiating a series of transactions … .

35. In re Bilski (Fed. Cir. 2008)
• The § 101 inquiry
– If a claim preempts substantially all uses of
a fundamental principle, it is unpatentable
subject matter
– If a claim preempts only a particular
application of a fundamental principle, it is
patentable subject matter

36. In re Bilski (Fed. Cir. 2008)
• Federal Circuit applies a machine-or-
transformation test to determine
preemption of a fundamental principle
– A claimed process is directed to patentable
subject matter under § 101 if it:
(1) is tied to a particular machine or
apparatus; or
(2) transforms a particular article into a
different state or thing

37. Diagnostic Tools and Personalized
Medicine: The Future of Biotechnology?
Health Care in the 21st Century
P4 Medicine:
• Predictive
• Preventive
• Personalized
• Participatory
Lee Hood, M.D., Ph.D.
President
Institute for Systems Biology

38. Diagnostic Tools and Personalized
Medicine: The Future of Biotechnology?
• Genomic Personalized Medicine
– Information about a patient's genotype
or gene expression profile used to tailor
medical care
• Provide a specific therapy for an individual's
disease
• Initiate a preventative measure suited to an
individual
• “Rational drug design" based on knowledge of
disease pathophysiology

39. Vioxx May Increase the Risk of Heart Attacks
and Strokes -- Arthritis Drug Vioxx Taken Off the
Market as Unsafe
• WASHINGTON, D.C. — October 4, 2004 — A major drug manufacturer,
Merck, has withdrawn its painkiller Vioxx (rofecoxib) from the market
because it may increase the risk of heart attacks and strokes (FDA News,
September 30, 2004). Vioxx is a nonsteroidal anti–inflammatory drug
(NSAID) that blocks the enzyme COX–2. The Food and Drug
Administration (FDA) approved the drug in 1999 to relieve arthritis
symptoms, severe pain in adults, and painful menstrual cycles.
• Merck’s decision to halt Vioxx sales is based on data from a long–term
clinical trial to see if Vioxx could be effective in preventing new polyps
from forming in colon cancer patients. The researchers stopped the
study when they discovered that patients who took Vioxx had a greater
risk of heart attacks and strokes than those who took a placebo (a sugar
pill). The increased risk was particularly great in patients who had been
taking Vioxx for more than 18 months.

40. Diagnostic Tools and Personalized
Medicine: The Future of Biotechnology?
• A method for detecting in a patient a Vioxx-
associated risk of heart attack, said method
comprising the step of:
- identifying in said patient a mutation in a
“Vioxx risk gene,”
wherein the presence of said “Vioxx risk
gene” indicates an increased probability in
said patient of heart attack following the
administration of Vioxx

41. Classen v. Biogen (DC MD 2006)
• Classen ‘283 Patent claims:
– A method of determining whether an
immunization schedule affects the
incidence or severity of a chronic immune-
mediated disorder…, comprising
• immunizing …; and
• comparing the incidence of chronic immune
mediated disorders … relative to a control group

42. Classen v. Biogen (DC MD 2006)
• DC MD
– “The * + patent does not claim a specific technique
or technical process of testing [ ] safety
– Instead, the [ ] patent describes only a general
inquiry of whether the proposed correlation
between an immunization schedule and the
incidence of chronic disorders exists
– As such, the process is indistinguishable from the
idea itself
– Accordingly, the [ ] patent seeks to patent an
unpatentable natural phenomenon”

43. Classen v. Biogen (CAFC 2008)
• Federal Circuit
– “In light of our decision in In re Bilski … we affirm
the district court’s grant of summary judgment that
these claims are invalid under 35 U.S.C. 101
– Dr. Classen’s claim is neither ‘tied to a particular
machine or apparatus’ nor does it ‘transform a
particular article into a different state or thing’ ”
• Classen files a petition for writ certiorari to the U.S.
Supreme Court

44. Prometheus v. Mayo (SD CA 2008)
• Prometheus Claim 1
– A method of optimizing therapeutic
efficacy…, comprising:
• administering a drug providing 6-thioguanine to
a subject…; and
• determining the level of 6-thioguanine in said
subject … wherein
– 6-thioguanine less than about 230 pmol per 8x108
red blood cells indicates a need to increase the
amount of said drug
– 6-thioguanine greater than about 400 pmol per 8x108
red blood cells indicates a need to decrease the
amount of said drug

45. Prometheus v. Mayo (SD CA 2008)
• District Court
– Claimed correlations between certain thiopurine
drug metabolite levels and therapeutic efficacy and
toxicity are natural phenomena
• Result from innate metabolic activity in human
body
• Inventors did not “create” the correlation; the
correlation results from a natural body process
• Claims wholly preempt use of the correlations
– The only practical use of the correlation is in
drug treatment for autoimmune diseases

46. Prometheus v. Mayo (Fed. Cir. 2009)
• September 2009, Federal Circuit reverses
district court upholding patentability of
methods for calibrating a drug dosage
under 35 USC § 101

47. Prometheus v. Mayo (Fed. Cir. 2009)
• Federal Circuit, cont.
– Applying the Bilski Machine or
Transformation test, the required
administration of a drug “transforms an
article into a different state or thing.”
– Distinguish diagnosis claims that merely
require data gathering and correlation
rather than injection of drugs

48. Prometheus v. Mayo
• October 2009, Mayo files a petition for writ of
certiorari to the U.S. Supreme Court
• Question Presented
“Whether 35 U.S.C. § 101 is satisfied by a
patent claim that covers observed correlations
between patient test results and patient
health, so that the claim effectively preempts
all uses of these naturally occurring
correlations”

49. Bilski v. Kappos (S.Ct. 2010)
• June 28, 2010, Supreme Court affirms CAFC
Bilski decision
– The machine or transformation test is not the
exclusive test for patent eligibility, but in most
instances the existence of a machine or
transformation is highly relevant to the question of
patent eligibility
– Grants certiorari, Vacates the Federal Circuit’s
Classen and Prometheus decisions and Remands to
the Federal Circuit in view of its Bilski decision

50. Classen v. Biogen (CAFC 2011)
• August 31, 2011, on remand from S.Ct., CAFC affirms
prior decision
– “Methods that simply collect and compare data, without applying
the data in a step of the overall method, fail to traverse the § 101
filter.”
– Considered the “immunizing” step as the gathering of published
data
– Moore (dissent)
• Criticized majority for mischaracterizing the “immunizing
mammals” step as “reviewing the effects of known
immunization schedules.”
• Nonetheless, distinguishes Prometheus’ claims, which are
directed to administration of a specific compound for a specific
disease
• Petition for writ certiorari to the U.S. Supreme Court
due November 29, 2011

51. Prometheus v. Mayo (CAFC 2010)
• December 17 2010, on remand from S.Ct., CAFC
upholds claim validity
– Bilski provides broad – although not unlimited –
scope for patent protection, and “an application of
a law of nature or mathematical formula to a
known structure or process may well be deserving
of patent protection.”
– Patent eligibility rests on the specific treatment
steps recited by the claims: the “administering”
step and the “determining” step.

52. Prometheus v. Mayo (CAFC 2010)
• December 17 2010, on remand from
S.Ct., CAFC upholds claim validity
– “The inventive nature of the claimed methods
stems not from preemption of all use of these
natural processes, but from the application of a
natural phenomenon in a series of steps comprising
particular methods of treatment.”

53. Prometheus v. Mayo (CAFC 2010)
• December 17 2010, on remand from S.Ct., CAFC
upholds claim validity
– The asserted claims are “claims to methods of
treatment, which are always transformative, when one
of a defined group of drugs is administered to the body
to ameliorate the effects of an undesired condition.”
– The “determining” step is transformative because it
involves “some form of manipulation, such as the high
pressure liquid chromatography method specified in
several of the asserted dependent claims … ”
– The presence of “mental steps” does not “negate the
transformative nature of prior steps.”

54. Prometheus v. Mayo
• June 20, 2011, Supreme Court grants certiorari
• Question Presented:
– Whether 35 U.S.C. § 101 is satisfied by a patent
claim that covers observed correlations between
blood test results and patient health, so that the
claim effectively preempts all uses of the naturally
occurring correlations, simply because well-known
methods used to administer prescription drugs and
test blood may involve “transformations” of body
chemistry.
• Oral arguments heard on December 7, 2011

55. Prometheus v. Mayo
• Mayo’s Amicus Brief
– Prometheus's patent claims "preemp[t] all practical use of an
abstract idea, natural phenomenon, or mathematical
formula."
– “Recite a natural phenomenon—the biological correlation
between metabolite levels and health—without describing
what is to be done with that phenomenon beyond
considering whether a dosage adjustment may be necessary."
– The claims' drug-administration and metabolite-
measurement steps are merely "'token' and 'conventional'
data-gathering steps" that cannot establish subject-matter
eligibility.
– Patent protection is unnecessary to promote the
development of diagnostic methods like those claimed and
will in fact interfere with both their development and actual
medical practice.

56. Prometheus v. Mayo
• United States Solicitor General
– The claimed methods recite "patent-eligible subject
matter," and petitioners' objections to patentability
are properly understood as challenges to the
claimed methods' novelty and nonobviousness.

57. Prometheus v. Mayo
• Roche & Abbott
– Patents are crucial for innovation in personalized
medicine and … development diagnostic tests that
can enable such medicine's practice.
– Arguments "that patents on diagnostic tests stifle
innovation and basic scientific research" are
"largely based on speculation, rather than sound
evidence.“
– “Market-driven business practices and self-
enforcing market norms correct for any perceived
limitations on the accessibility of patented
diagnostic technologies.”

58. Myriad v. ACLU (NY FDC 2010)
• In May 2009, the ACLU filed a lawsuit against
the USPTO, Myriad Genetics, and the
University of Utah Research Foundation
• Challenged patents claiming the human
BRCA1/BRCA2 DNA and methods employing
the detection of the BRCA1/BRCA2
gene/mRNA for the diagnosis of breast and
ovarian cancer

59. Myriad v. ACLU (NY FDC 2010)
• Claims at Issue
– An isolated DNA coding for a BRCA1
polypeptide, said polypeptide having the amino
acid sequence set forth in SEQ ID NO: 2.

60. Myriad v. ACLU (NY FDC 2010)
• Claims at Issue
– A method for diagnosing a predisposition for breast
cancer in a human subject which comprises
• comparing the germline sequence of the BRCA2
gene or the sequence of its mRNA in a tissue
sample from said subject with the germline
sequence of the wild-type BRCA2 gene or the
sequence of its mRNA
wherein an alteration in the germline sequence of
the BRCA2 gene or the sequence of its mRNA of
the subject indicates a predisposition to said
cancer.

61. Myriad v. ACLU (NY FDC 2010)
• ACLU argued:
– “Because human genes are products of
nature, laws of nature and/or natural
phenomena, and abstract ideas or basic human
knowledge or thought, the challenged claims are
invalid under Article 1, section 8, clause 8 of the
United States Constitution and 35 U.S.C. § 101.”
– Art. 1, Sect. 8, Clause 8
“To promote the Progress of Science and useful Arts, by
securing for limited Times to Authors and Inventors the
exclusive Right to their respective Writings and
Discoveries”

62. Myriad v. ACLU (NYFDC 2010)
• March 29, 2010, Judge Sweet granted
Summary Judgment in favor of the ACLU
– Human genetic sequences and the scientific inquiry
of looking at a gene or comparing two genes are
not patentable
• constitutes a natural phenomena, a law of
nature, and abstract ideas

63. Myriad v. ACLU
• Decision appealed to the Federal Circuit
– Myriad Amicus Brief
• Composition of matter claims directed towards
isolated DNA molecules are patent eligible, in
part, because they have “markedly different
characteristics” than their naturally occurring
counterparts
– “Products of nature” are patentable and
have been held to be for nearly 100 years
– Such a “sweeping exception” would bar the
patenting of pharmaceuticals derived from
natural sources (e.g., Taxol)

64. Myriad v. ACLU
• Decision appealed to the Federal Circuit
– Myriad Amicus Brief
• Methods of diagnosis claims are patent
eligible, in part, because they all require
physical transformation of a DNA sample
(i.e., isolation, processing, and analysis) that
satisfies the Bilski machine or transformation
test
– NOTE: Compare Prometheus
» Methods that involve the processing of a
biological sample “necessarily involve a
transformation” and, thus, meet the
Bilski machine or transformation test

65. Myriad v. ACLU
• Department of Justice Amicus Brief
– Genomic DNA that has merely been isolated from
the human body, without further alteration or
manipulation, is not patent-eligible.
– The unique chain of chemical base pairs that
induces a human cell to express a cancer protein is
not a 'human-made invention.'
– Nor is the fact that particular natural mutations in
that unique chain increase a woman's chance of
contracting breast or ovarian cancer."

66. Myriad v. ACLU (CAFC 2011)
• July 29, 2011, Federal Circuit
– Affirms NY District Court
• Method claims directed to “comparing” or “analyzing”
DNA sequences are patent ineligible because they do not
include a transformative step and cover only
abstract, mental steps
– Reverses NY District Court
• Composition claims to “isolated” DNA are patent eligible
since the molecules as claimed do not exist in nature

67. Myriad v. ACLU (CAFC 2011)
• CAFC Distinguishes “Isolated” and “Purified”
– Isolated = Patent Eligible?
• The claimed “isolated” molecule has “a markedly
different chemical structure” or “a distinctive chemical
identity and nature” from a molecule that exists in nature
• “Isolated” molecules are “manipulated chemically” …
“chemically cleaved from their chemical combination with
other *+ materials” as exists in nature … differences “are
directly related to the change in chemical bonds.”
– Purified = Ineligible?
• “Purification makes pure what was the same material, but
was previously impure”
• “Mere purification of a naturally occurring element is
typically insufficient to make it patentable subject
matter”

68. Myriad v. ACLU (S.Ct.)
• October 12, 2011, ACLU announces
decision to petition U.S. Supreme Court
for writ of certiorari
• Petition filed on December 7, 2011

69. Post Myriad Point-
Counterpoint
• Patents give a monopoly to one company,
which makes the costs of products and
diagnostic tests prohibitively expensive for
those without insurance
vs.
• Without patents, companies have a greatly
reduced incentive to take risk and, as a
consequence, are less likely to invest in the
development of products and diagnostic tests

70. Practice Tips
• Product Claims
– Draft claims to “isolated” rather than “purified” products
• Describe in specification how “isolated” product is
structurally and chemically distinct from what is found in
nature
• Describe in specification new uses or functions for the
claimed product as compared to a natural product in its
natural environment.
– Draft claims to commercial embodiments
• Compositions and /or kits comprising “isolated” or
“purified” products
• Hybrid and fusion molecules
• Vectors
• Recombinant cells

71. Practice Tips
• Method Claims
– Draft method claims that recite a transformative step
• Administering a compound
• Isolating or purifying a sample
• Determining a sequence (avoid a solely mental step)
• Detecting a molecule
– Draft method claims that recite the use of a machine in a
method step
• Apparatus used to sequence a nucleic acid or protein
• Device to measure a particular parameter.
– Draft method claims that include an end result step that
follows an analysis or comparison
• Adjusting a dosage
• Performing a treatment protocol

72. Stay Tuned …
Thank You!
Gary M. Myles, Ph.D.
gmyles@merchantgould.com
(206) 342-6226

74. Market Capitalization

78. US National Biotech Clusters

81. Top US Companies
by Market Capitalization (Oct 2007)
• Exxon Mobil $511B
• General Electric $414B
• Microsoft $328B

82. • Therapeutic Proteins
are expressed through
Recombinant DNA
Technology
Recombinant Protein

83. Seattle Biotechnology Products Approved
for Marketing by the FDA
Enbrel Immunex/Amgen Rheumatoid Arthritis Nov 1998
Cialis ICOS/Eli Lilly Erectile Dysfunction Nov 2003
Recothrom ZymoGenetics Surgical Bleeding May 2008
BEXXAR Corixa/GlaxoSmithKline CD20-positive May 2008
Non-Hodgkins Lymphoma
Provenge Dendreon Prostate Cancer Apr 2010

84. Recombinant Proteins as Therapeutics
• Rheumatoid Arthritis

85. Recombinant Proteins as Therapeutics
• Cytokines, such as
tumor necrosis
factor, promote an
inflammatory response
• Causes the clinical
problems associated
with autoimmune
disorders such as
rheumatoid arthritis

87. Enbrel – Soluble TNF-R

88. Recombinant Proteins as Therapeutics
• Enbrel (Immunex/Amgen)
– Recombinant soluble TNFα-R
– Binds soluble, extracellular TNFα thereby
preventing its binding to cellular TNF α-R
– Therapeutic efficacy for the auto-immune
disease rheumatoid arthritis (RA)

89. Immunex
U.S. Patent Nos. 5,712,155 and 5,945,397
An isolated DNA sequence selected from the group consisting of:
(a) a DNA sequence that encodes a polypeptide having the amino
acid sequence selected from the group consisting of amino acids 1 to X
of FIG. 2A and amino acids 1 to 233 of FIG. 3A, wherein X is an amino
acid from 163 to 235; and
(b) a DNA sequence capable of hybridization to the complement of
the DNA sequence of (a) under moderately stringent conditions
(50oC., 2x SSC) and which encodes a polypeptide that is capable of
binding to TNF and which is at least 88% identical to a polypeptide
encoded by the DNA of (a).
A composition consisting essentially of a protein comprising a sequence of
amino acids selected from the group consisting of amino acids 1-163 of
SEQ ID NO:2 and amino acids 1-233 of SEQ ID NO:4, wherein said
protein is capable of binding TNF.

90. Antibodies

91. Antibody Therapeutics
Target Mouse Ab (IgG) Chimeric Ab
Ag (Variable region is exchanged)
Humanized Ab
CH1 CH1 CH1 CH1 1st Generation
CL CL CL CL (CDRs exchanged)
CH2 CH2 CH2 CH2
1975 1983
CH3 CH3 CH3 CH3 CH1 CH1
CL CL
CH2 CH2
1986
CH3 CH3
CH1 CH1
CL CL CH1 CH1
CL CL
Fully human CH2 CH2
Ab CH2 CH2
1988
1990s CH3 CH3 Humanized Ab – 2nd Generation
CH3 CH3 (CDRs / FW residues exchanged)

92. Anti-CD20 Antibodies
• Non-Hodgkin’s Lymphoma
– B-cells expressing CD20, a phosphoprotein
found on the surface of >90% of B cells
from peripheral blood or lymphoid organs

93. Rituxan

94. Bexxar
(Corixa/GlaxoSmithKilne)

95. Corixa
U.S. Patent No. 6,015,542
A composition comprising:
(1) a radioactively labelled monoclonal antibody or radioactively
labelled monoclonal antibody fragment in an amount providing 1
to 200 mCi of radioactivity and providing irradiation in a dose
range of 10 to 200 cGy [Rads] to the whole body of a human
patient, said amount being effective for achieving remission of B-
cell lymphoma in the patient, wherein said antibody or said
antibody fragment binds to CD20 antigen present on the surface
of cells of B-cell lymphoma and wherein the amount of
radioactivity that labels the antibody or antibody fragment is less
than the amount which causes myelosuppression severe enough
to require the reintroduction of hematopoietic stem cells into
said patient in order for the patient to recover hematopoietic
function, and
(2) a pharmaceutically acceptable carrier.

96. Biotechnology vs.
Pharmaceutical
• Biotechnology: The use of biomolecules
to treat disease
• Pharmaceutical: The use of small
molecules to treat disease

97. What are Biomolecules?
• Genetic Material
– DNA
– RNA
• Proteins
– Receptors and Ligands
– Enzymes
– Antibodies
• Lipids
• Carbohydrates