PHAR 6766: Biotechnology-Derived Drugs
Course Syllabus Fall 2016
1.0 Credits
This course adheres to the College of Pharmacy Central Syllabus. Please see the following link for this information:
https://docs.google.com/a/umn.edu/document/d/1artQ5e1rbzxe8lEtWo7BE8k8snZAEgMMz_QcW8yJ-II/edit?pli=1
Course Web Site: http://moodle.umn.edu
Term: Fall PD3
Dates: Tuesday, August 22 to Friday, October 7, 2016
Time
Day
Duluth Room
Twin Cities Room
(except as indicated)
(except as indicated)
Tuesday
10:10 – 12:05
LSci 165
MoosT 1-450
Friday
2:30 – 3:20
Lib 410
WDH 7-135
Course Instructional Team (in order of appearance):
Name
Office Location
Phone
Email
Preferred
contact
Office
hours
Tom Shier
(TC) 8-168
WDH
612-624-9465
[email protected]
either
Open
door
Yao Yao
(D) 117 LSci
218-726-6082
[email protected]
e-mail
By
appoint
ment
Pamala
Jacobson
(TC) 7-151
WDH
612-624-6118
[email protected]
either
By
appoint
ment
Steve
Schondelmeyer
(TC) 7-159
WDH
612-624-9931
[email protected]
e-mail
By
appoint
ment
Tim Stratton
(D) 209 LSci
218-726-6018
[email protected]
e-mail
By
appoint
ment
Lowell Anderson
(TC) 7-172
WDH
612-626-5158
[email protected]
email
By
appoint
ment
Teaching Assistants:
G.T.A. (Duluth): Lucas Solano, [email protected]
G.T.A. (Twin Cities): Michael Grillo, [email protected]
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Overview of the course
Course content:
In 2013, seven of the eight top drugs by sales were recombinant DNA-derived drugs. Sales numbers are not as
important to pharmacies as number of scripts filled, but they do matter, because that is where the pharmaceutical
industry is going to make its investments going forward. The pipeline for biotechnology drugs isn’t empty, so we
can expect more of these agents will be brought to market in the future. Pre-filled syringe formulations are bringing
more and more of these drugs into community pharmacies. Biotechnology-derived drugs are key participants in
several important clinical areas, such as arthritis, kidney diseases and oncology, and more penetration into other
fields can be expected. Biotechnology-derived drugs are where the future is, and pharmacy students need to
understand how they are made, how they act and what special considerations are involved. This course will
provide the foundational knowledge necessary to understand, recommend and counsel patients on current
biotechnology-derived drugs and provide the basis for self-education needed to appreciate the biotechnologyderived drugs of the future.
This course will also prepare pharmacists to assist patients with self-administered protein drug medications (e.g.,
insulin) and in the use and interpretation of home diagnostic monoclonal antibody kits (e.g. pregnancy and
ovulation test kits). The material covered in this course will provide valuable background information about drugs
used in strategically aligned modules/courses, including the diabetes clinical module; dermatology; genetics;
immunology; cardiovascular; neurology (multiple sclerosis); oncology; infectious diseases; and inflammatory
diseases (arthritis).
Course format
Class will meet for 50-minute sessions, three times per week, for the first half of the semester. Class time will be
used for lectures and various types of in-class learning activities (discussion, problem-solving, small group,
etc.). In the clinical topic sessions, class sessions will include clinical case study activities and may include student
response system (clicker) participation, and Team-Based Learning (TBL) activities. Students should plan to spend
2 hours outside of class for every 1 hour in class for this course.
Prerequisites
Successful completion of Integrated Biochemical Sciences, Principles of Medicinal Chemistry, Principles of
Pharmacology, Immune System and Infectious Disease, Cellular Metabolism and Nutrition, and Integrated
Endocrinology.
Course Materials
There is no required textbook at this time. If a suitable, focused text in the subject appears, it will be considered
for adoption.
Computer/Technology Requirements
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Moodle: This course will use Moodle to distribute learning materials. See an introduction to Moodle at
http://uttc.umn.edu/training/tutorials/moodle/orientation/moodle-introduction/index.htm
E-Textbooks: There are no E-Texts at this time. You will access these through the course Moodle site, if
they become available.
E-Mail: Course instructors may communicate through email about course administrative issues. You
should check your U of M email daily.
Student-response systems: Discussions may use Turning Point or other adopted audience response
2
system software. You may need a Turning Point clicker or app.
Course Goals & Objectives
Concepts/Goals/Objectives
Concept 1: Biotech-derived drugs are different from other drugs.
Course goal 1: Explain ways in which biotech-derived drugs differ from other drugs.
Learning Objective (LO) 1a: Compare and contrast properties of biotechnology-derived drugs and properties
of small-molecule drugs; and describe how the differing properties affect drug storage, preparation, and
administration methods.
LO 1b: Explain site-directed mutagenesis and directed evolution, and how these techniques can be used to
produce second generation biotechnology-derived drugs.
LO 1c: Describe how a mouse monoclonal antibody can be re-engineered to minimize its immunogenicity by
making it look human.
LO 1d: Explain how receptors are made to look and act like antibodies (pseudoantibodies), and the limitations
of this method for making other drugs.
LO 1e: Detail the mechanisms of action for some important biotechnology-derived drugs.
LO 1f: Explain how the pharmacokinetics of biotechnology-derived drugs can be improved to make second
generation drugs by the following:
(i) pegylation; (ii) altering glycosylation; (iii) altering the molecular weight and (iv) altering solubility
LO 1g: Describe the legal and economic considerations for the production of generic biotechnology-derived
drugs (biosimilars).
Concept 2: Biotechnology drugs are important to pharmacy.
Course goal 2: Explain how and why biotechnology drugs are important to pharmacy.
LO 2a: Describe the basic tools used by scientists to clone genes and transform them into biotechnologyderived drugs.
LO 2b: Explain how biotechnology-derived drugs can be made more effective by structure modification.
LO 2c: List clinically important drugs that have been discovered because of the availability of site-directed
mutagenesis.
LO 2d: Describe the localization techniques used to diagnose disease with monoclonal antibody-based
imaging diagnostics.
LO 2e: Outline DNA sequencing from research tool to genome sequencing for individualized patient care.
LO 2f: Describe how DNA-based aptamers work, why they are of interest, how they are made, and how they
compare in effectiveness with protein-based antibodies.
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Concept 3: Biotechnology-specific clinical skills are needed for practice.
Course goal 3: Apply knowledge of biotech-derived drugs to patient care.
LO 3a: Explain who, how and why erythropoietin, growth hormone and sometimes insulin are abused.
LO 3b: Explain how home diagnostic kits work.
LO 3c: Outline the potential and limitations of gene and cell-based experimental therapies and what limits
their use.
LO 3d: Explain the high cost of biotechnology-derived drugs, and how that cost affects reimbursement,
inventory practice and counterfeiting.
LO 3d: Describe the qualities of a biosimilar drug, approval process and cost implications
LO 3f: Analyze the ethical issues around the use of biotechnology drugs
Attendance Policy
Students are expected to attend every class for which they are registered. Students are expected to attend classes
on the campus where they are enrolled. Although instructors may choose to take attendance, it is recognized that
sometimes students will need to attend to other obligations, and on those occasions they will listen to the recorded
version of the lecture on their computer.
Expectations
You are expected to participate actively in your own education while in the College of Pharmacy. This will prepare
you to be a lifelong learner.
Assessments and Grading
The following graded assessments will count toward your final grade for this course in the following amounts:
#
Date
Title
Brief description
Assessment Goal
(required to link to domain)
Points
%
of
final
grade
1
Week 4
Exam 1 (Lectures 1-7)
Learning Objective 1-2
85
42.5%
2
Week 8
Exam 2 (Lectures 8 - end)
Learning Objective 1-3
93
46.5%
3
Weeks 6 and
7
Active learning activities
Learning Objective 3
20
10%
4
Last Week
Complete a course evaluation
2
1%
You will complete two in-class exams (50 minutes), worth 85 and 93 points. The dates of these exams are
announced in the course schedule.
All exam answers must be written in ink. Five points will be deducted from exams not written in ink.
REGRADE POLICY
All exams submitted for regrade must have a written explanation attached detailing the need for the exam to be
regraded. The request must be submitted to the instructor within one week of receiving the graded exam. No
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changes will be made in the final grade without the consent of the course faculty. Regrading exams may also
result in point deductions, if overlooked grading errors are found.
MAKE-UP EXAM POLICY
Under no circumstances will make-up exams or in-class discussion sessions be scheduled for unexcused
absences. Excused absences include 1) illness verified by a physician's letter, 2) serious family emergency, and
3) a University-sponsored event, verified by a note from the leader of the sponsoring institution. Notification of the
course director must occur in advance of the regularly scheduled exam.
HONOR CODE
Each student is bound by the following specific provisions as part of the Code: Academic misconduct is any
unauthorized act which may give a student an unfair advantage over other students, including but not limited to:
falsification, plagiarism, misuse of test materials, receiving unauthorized assistance and giving unauthorized
assistance. Each student will be asked to sign a cover sheet on tests and written assignments that reaffirms the
honor code as it applies to this course. Specifically, each student will be required to do their own work on all tests
and written assignments. For written assignments, students are allowed to discuss the assignment with other
students, but all written material must be their own work and not the result of group discussions.
Grading Information
Grades will be assigned at the end of the term and will be based on the total number of points out of a maximum
of 200 points. See the grades table below. To pass the course you must obtain 60% of the total points.
Incomplete grades will be given only by prior arrangement approved by the course director.
Quiz and Exam Policies
●
●
●
●
●
●
All in class written exams will be given during scheduled class time.
Exams will not be graded on a curve.
The use of electronic devices such as cell phones, tablets, PDAs, pocket computers, programmable
calculators, and other devices with electronic data bases is not permitted during written exams unless
specified by course director.
Exams will be comprehensive and will build on previous content. Standard analyses of composite class
responses for all exam questions will be conducted by the authors of those exams prior to releasing the
scores.
An opportunity to request an exam regrade is provided for all exams system.
Grades will not be given out over the telephone or by email.
Course Letter Grades
Grade
Percentage
A
93.0 - 100
A-
90.0 - 92.99
B+
87.0 - 89.99
B
83.0 - 86.99
B-
80.0 - 82.99
5
C+
77.0 - 79.99
C
73.0 - 76.99
C-
70.0 - 72.99
D
60.0 - 69.99
F
0 - 59.99
Detailed Course Outline & Schedule*
* Subject to change at course director's discretion.
Class
Sessions
Agenda/Topics
Competency
Learning
Objective
Activities /
Assignmen
ts/
Assessme
nts
Week 1:
Tuesday,
August 23, 2016
Lecture 1
(Shier)
Introduction to biotechnology drugs
Topics:
Importance of Biotech drugs; sales in 2013; special challenges with biotech
drugs: Stability (3 slides, covered by Panyam); handling and storage; IV
administration, pre-filled pens (DX: Pegasys, Humalog); adverse effects;
immunogenicity; financial issues; lack of generics (biosimilars coming)(DX:
Growth Hormone); counterfeit drugs (DX: bevacizumab; filgrastim); large
synthetic peptides (DX: Byetta; Angiomax, Forteo; Fuzeon); drugs of abuse
(DX: Erythropoetin; Growth Hormone).
Learning
Objectives
1a, 1g,
Lecture,
Discussion
Week 1:
Tuesday,
August 23, 2016
Lecture 2
(Shier)
Recombinant DNA toolkit I
Topics:
Refresher on DNA, gene structure; enzyme tools: restriction endonucleases,
polymerases, ligase, reverse transcriptase; DNA probes; PAGE, blots
Learning
Objectives
1b, 2a, 2b,
Lecture,
Discussion
Week 1:
Friday, August
26, 2016
Lecture 3
(Shier)
Recombinant DNA toolkit II
Topics:
PCR; qPCR; DNA sequencing; automation of DNA sequencing; Next-Gen DNA
sequencing; human genome project.
Learning
Objectives
1b, 2a,
Lecture,
Discussion
Week 2:
Tuesday,
August 30, 2016
Lecture 4 (Yao)
DNA: from gene cloning to drugs
Topics:
DNA cloning (DX: Growth Hormone; Erythropoetin); PCR cloning; expression
vectors; expression of bacterial proteins, mammalian proteins; industrial
production; drug formulation; gene pharming (DX: ATryn).
Learning
Objectives1
b, 2a,
Lecture,
Discussion
Week 2:
Tuesday,
August 30, 2016
Lecture 5 (Yao)
Site-directed mutagenesis; directed evolution
Topics:
Site-directed mutagenesis (DX: Inferogen); directed evolution/phage display
(DX: Humira); protein engineering
Learning
Objectives
1b, 2a, 2b,
Lecture,
Discussion
Week 2:
Monoclonal antibody production
Topics:
Learning
Objectives
Lecture,
Discussion
6
.
Friday,
September 2,
2016
Lecture 6 (Yao)
Antibody refresher; mono vs polyclonal antibodies; Kohler and Milstein
production; MoAbs from phage display (DX: Humira); commercial scale up
production
1c, 1d, 2a,
2b,
Week 3:
Tuesday,
September 6,
2016
Lecture 7 (Yao)
Diagnostics: monoclonal antibodies and DNA-based
Topics:
Early pregnancy test kits and how they work; other types of kits; mouse
monoclonals in diagnosis (DX: Tositumomab); DNA probe assays and PCR;
FISH; companion diagnostics (DX: Trastuzumab).
Learning
Objectives
1c,
1d, 2a, 2d,
3b
Lecture,
Discussion
Week 3:
Tuesday,
September 6,
2016
Lecture 8
(Shier)
Humanized monoclonal antibodies
Topics:
IgG refresher; engineered MoAb types (DX: infliximab; adalimimab);
pseudoantibodies (DX: etanercept; aflibercept; alefacept; abatacept; rilonacept;
belatacept); peptibody drugs (DX: romiplastim); phage display (DX: adalimimab)
Learning
Objectives
1d, 2a, 2b,
2c, 2d
Lecture,
Discussion
Week 3:
Friday,
September 9,
2016
Exam 1: Lectures 1 - 7
Week 4:
Tuesday,
September 13,
2016
Lecture 9
(Shier)
Novel therapies, including gene and cell-based therapies
Topics:
Antisense and siRNA drugs (DX: Fomivirsen sodium); gene therapy; aptamers
(DX: Pegaptanib sodium; ranibizumab; bevacizumab; aflibercept); cell therapy
(DX: Sipuleucel-T); immunotherapy with targeted T-cells; stem cell therapy.
Learning
Objectives
2a, 2b, 2e,
2f,
Lecture,
Discussion
Week 4:
Tuesday,
September 13,
2016
Lecture 10
(Shier)
Recombinant and DNA Vaccines
Topics:
Structural issues with HBV (DX: Recombivax HB; Engerix-B®, Twinrix® ,
Pediarix®); HPV (DX: Gardasil; Cervarix®); influenza (DX: FluBlok); emerging
viruses; DNA vaccines; canarypox veterinary vaccines (DX: Recombitek ®);
targeted virus therapies;
Learning
Objectives
2a, 2c, 2e
Lecture,
Discussion
Week 4:
Friday,
September 16,
2016
Lecture 11
(Shier)
Pharmacology of recombinant DNA-derived drugs – Part 1
Topics:
Transmembrane signaling mechanisms; receptor binding (DX: insulin; PDGF;
EGF; erythropoietin; peginesatide); signal transduction mechanisms through the
membrane; JAK-STAT pathway; Src-kinase pathway; nuclear response
element activation; anti-VEGF mechanism (DX: bevacizumab, romiplastim);
antibody-mediated cell killing mechanisms (DX: rituximab); apoptosis triggering
mechanisms (DX: rituximab, trastuzumab)
Learning
Objectives
1e, 2a,
2b, 2c,
Lecture,
Discussion
Week 4:
Tuesday,
September 20,
2016
Lecture 12
(Shier)
Pharmacology of recombinant DNA-derived drugs – Part 2
Topics:
interferon mechanisms (DX: Intron® A, Betaseron®, Avonex®, Rebif®,
Actimmune®); anti-TNFα mechanisms (DX: infliximab; adalimimab, etanercept);
action of insulins, GLP-1 agonists (DX: ); MS drug mechanisms (DX: ); other
Learning
Objectives
1e, 2a,
2b, 2c,
Lecture,
Discussion
Week 5:
Second generation biotechnology drugs: pegylation et al.
Topics:
Learning
Objectives
Lecture,
Discussion
written
exam
7
Tuesday,
September 20,
2016
Lecture 13
(Shier)
Second generation drugs; eliminating unnecessary molecule parts (DX:
Alteplase, Reteplase, Tenecteplase); improving pharmacokinetics by
pseudoantibody or peptibody formation (DX: ); improving pharmacokinetics by
pegylation (DX: pegvisomant, pegfilgrastim, pegaptanib sodium, peginterferon
alfa 2a & 2b); improving pharmacokinetics by increased glycosylation for
increased half-life (DX: erythropoietin and darbepoetin); random structure
variation and evaluation of properties (DX: Humulin®, Insulin Lispro, Insulin
aspart, Insulin glargine Insulin glulisine, Insulin detemir); consensus sequences;
lysosome-targeting of glycoproteins (DX: ); immunotoxin drugs (DX: adotrastuzumab emtansine); fusion toxins (DX: denileukin diftitox).
2a, 2b, 2c,
2e, 1f,
Week 5:
Friday,
September 23,
2016
Lecture 14
(Jacobson)
Biosimilars
Topics:
Biosimilars are biological products that are demonstrated to be “biosimilar” to or
“interchangeable” with an FDA-licensed biological product; difference between
generic drugs and biosimilars. E.g. Zarxio (filgrastim-sndz).
..
Learning
Objectives
2b, 2c, 2e
Lecture,
Discussion
Week 6:
Tuesday,
September 27,
2016
Lecture 15
(Schondelmey
er)
Costs of biotechnology drugs
Topics:
Reasons for high cost agents, specialty pharmacies, prior approvals ex: multiple
sclerosis, cancer, RA drugs.
Learning
Objectives
1g, 3c, 3d
Lecture,
Discussion
Week 6:
Tuesday,
September 27,
2016
Lecture 16
(Jacobson)
Clinical Applications of Common Biotechnology Agents
Topics:
Biotechnology-derived drugs used in the treatment of cancers and inflammatory
diseases
Learning
Objectives
1g, 3d, 3e,
Case
studies,
active
learning
Week 6:
Friday,
September 30,
2016
Lecture 17
(Jacobson)
Biotechnology drug case discussions
Topics:
Biotechnology-derived drugs used in the treatment of cancer e.g. breast cancer,
colorectal , melanoma, lymphoma
Learning
Objectives
1g, 3d, 3e
Case
studies,
active
learning
Week 7:
Tuesday,
October 4, 2016
Lecture 18
(Jacobson)
Biotechnology drug case discussions
Topics:
Biotechnology-derived drugs used in the treatment of infections and
inflammatory diseases e.g. rheumatoid arthritis, psoriasis, spondylitis, Crohn’s
disease, transplantation .
Learning
Objectives
1g, 3d, 3e
Case
studies,
active
learning
Week 7:
Tuesday,
October 4, 2016
Lecture 19
(Stratton/
Anderson/
Jacobson)
Case discussions on ethics around the use of biotechnology agents
Topics:
Case discussion on the use of high cost agents, impact on society,
considerations for inclusion on formularies, the healthcare system and payers,
allocation of resources, rare diseases, health disparities, etc.
Learning
Objectives
1g, 3d, 3e
Case
studies,
active
learning
Week 7:
Exam 2: Lectures 8 - 19
written
exam
8
Friday, October
7, 2016
Additional Policy Sources:
University of Minnesota and College of Pharmacy Policy Reference (Centralized
Syllabus)
[This page includes all required UMN and CoP policies, e.g., Academic Freedom; Copyright; Course
Evaluations; Disability Accommodations; FERPA, etc.]
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