Transcript Types of Vaccines and Patentability Considerations

United States Patent and
Trademark Office
Types of Vaccines
and
Patentability Considerations
Christina Chan
Supervisory Primary Examiner
Art Unit 1644
Phone: 571-272-0841
E-mail: [email protected]
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Acquisition Of Passive And Active
Immunity

Type
Acquired through

Passive Immunity
Natural maternal antibody
Immune globulin
Humanized monoclonal antibody
Antitoxin

Active immunity
Natural infection
Vaccines
Attenuated organisms
Inactivated organisms
Purified microbial macromolecules
Cloned microbial antigens
Expressed as recombinant protein
As cloned DNA alone or in virus vectors
Multivalent complexes
Toxoid
Immunology, Kuby
5th Ed. 2003, Page 416
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Vaccine

Merck Manual of Diagnosis and Therapy (17th
Ed., page 1097, 1999)
 A suspension
of whole (live or inactivated) or
fractionated bacteria or viruses that have been
rendered non-pathogenic, is given to induce an
immune response and prevent subsequent disease.
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Vaccine
Therapeutic vaccine
e.g. Therapeutic vaccine for HPV – associated
cervical carcinoma.
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Designing Vaccines

The development of an immune response does not necessarily mean that a state
of protective immunity has been achieved
- humoral response
- cell-mediated response

The development of immunologic memory
- Vaccine induces protective primary
immune response but fails to induce the formation of memory cells.
- incubation period of pathogens.
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Whole- Organism Vaccines

Attenuated (avirulent) viral or Bacterial vaccines.
e.g. – Smallpox vaccine - Typhoid Vaccine
- Measles vaccine - Polio (Sabin) vaccine

Inactivated (killed) viral or Bacterial vaccines.
e.g. – Salk injectable poliomyelitis vaccine (IPV)
- Hepatitis A vaccine
- Influenza vaccine
- Rabies vaccine
- Anthrax vaccine
- Cholera vaccine
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Comparison of attenuated (live) and
inactivated (killed) vaccines
Characteristic Attenuated vaccine
Inactivated vaccine
Production
Selection for avirulent organisms:
Virulent pathogen is inactivated by
virulent pathogen is grown under
chemicals or irradiation with gamma-rays
adverse culture conditions or
prolonged passage of a virulent
human pathogen through different hosts
Booster requirement
Generally requires only a single booster
Requires multiple boosters
Relative stability
Less stable
More stable (advantageous for Third
World countries where refrigeration is limited)
Produces mainly humoral immunity
Type of immunity induced Produces humoral and cell-mediated
immunity
Reversion tendency
Immunology, Kuby
4th Ed. 2000, page 455
May revert to virulent form
Cannot revert to virulent form
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Purified Macromolecules Vaccines
 Polysaccharide
vaccines
e.g. – Pneumovax 23 (23 distinct capsular polysaccharides)
 Toxoid
vaccines
e.g. Tetanus (inactivated exotoxin)
 Recombinant
surface antigen vaccines
e.g. – Hepatitis B surface antigen vaccine
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Other Types of Vaccines
Recombinant – Vector Vaccines
e.g. - Vaccinia virus
Synthetic Peptide Vaccines
Multivalent Subunit Vaccines
DNA Vaccines.
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A DNA Vaccine is …

A DNA molecule which induces a protective or
prophylactic immune response.

A critical feature of DNA vaccine is that it does
not replicate in the human or animal body (see
Paul, Fundamental Immunology, 4th Edition,
1999)
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DNA Vaccines - Advantages

DNA encoded antigens are expressed in the host
in its natural form – there is no denaturation or
modification
 inexpensive
 stable
 easy
to manipulate
 Can induce both humoral and cell-mediated response.
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Patentability Considerations in
Vaccine Art
 35
USC 101
 utility




35 USC 112 first paragraph
 enablement and written description
35 USC 112 second paragraph
 Definiteness
35 USC 102
 anticipation
35 USC 103
 obviousness
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Utility Considerations-DNA vaccine
Is the utility specific, substantial and credible?
 Well established utility.

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A DNA vaccine comprising an isolated nucleic acid
molecule encoding a protein comprising the amino
acid sequence of SEQ ID NO:1.

Specification:
 The
only disclosed utility for the protein or
DNA is for preventing HIV infection.
 There
is no other disclosure of any chemical,
physical, or biological properties of the protein.
 There
are no working examples that
demonstrate the specifically asserted utility.
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A DNA vaccine comprising an isolated nucleic acid
molecule encoding a protein comprising the amino
acid sequence of SEQ ID NO:1.
Analysis:

Is there a "well established utility" for the claimed
invention?
 No
- the specification as filed does not disclose or
provide evidence that points to an activity for the
protein or DNA and furthermore there is no art of
record that discloses or suggests any activity for the
claimed vaccine.
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A DNA vaccine comprising an isolated nucleic acid
molecule encoding a protein comprising the amino
acid sequence of SEQ ID NO: 1.
 Is

the asserted utility specific?
Applicant has made an assertion of utility for the
specifically claimed invention - preventing HIV infection,
which clearly defines a use that depends upon the particular
protein disclosed. Therefore, the utility is specific.
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A DNA vaccine comprising an isolated nucleic acid
molecule encoding a protein having the amino acid
sequence of SEQ ID NO:1.

Is the asserted utility substantial?
 Since
preventing HIV infection is a desirable outcome
based upon a need in the art, the disclosed use of the
claimed protein is substantial and “real world”.
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112 1st Paragraph – Enablement consideration

112 1st Paragraph - Enablement
 Does
one skilled in the art know how to make and use
the claimed invention?
 Wands analysis (MPEP 2164)
- Current state of the art.
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Example O from the Enablement
Training Slides

Claims:
A peptide consisting of the following amino acid
sequence: Ser Thr Ile Phe Leu Glu Ser Thr His Glu
Asp Ile Ser Glu Ala Ser Glu.
2. A vaccine comprising the peptide of claim 1 and a
pharmaceutically acceptable carrier.
3. A method of inducing an immune response in a host
comprising administering to the host a composition
comprising the peptide of claim 1 and a carrier.
1.
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Example O, Cont.

The specification relates to Lysobacteria erythrosis,
the microorganism which causes erythrosis, a slow
acting yet deadly disease manifested by the lysis of
the erythrocyte in patients infected with the
microorganism. The disclosure states that L.
erythrosis has many proteins on the surface thereof
and that one of these proteins in particular can
induce the immune system to produce antibodies.
The specific surface protein disclosed includes the
following peptide which is responsible for the
production of the antibodies: Ser Thr Ile Phe Leu Glu
Ser Thr His Glu Asp Ile Ser Glu Ala Ser Glu
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Example O, Cont.

The specification describes compositions including
the peptide and a carrier and teaches that the
composition can be used to induce the immune
system, e.g., to produce antibodies which will serve
to vaccinate the host against erythrosis without
causing the disease itself. Specific pharmaceutically
acceptable carriers are described as are specific
concentrations of the peptide in the compositions
and suitable modes of administration for generating
the immune response.
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Example O, Cont.

The specification includes one example which
synthesizes the peptide, places the peptide in a
carrier, injects the composition into a rabbit three
times over a period of two months. Three days after
the last injection, the rabbit was bled and antibodies
against erythrosis were isolated. The antibodies were
contacted with blood samples from normal patients
and those diagnosed with erythrosis. Binding was
present in the samples from the patients with
erythrosis but no binding was present in the samples
from normal patients.
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Example O, Cont.

State of the Prior Art: Diagnostic
assays for erythrosis are known in the
art. Those assays typically utilize
antibodies against surface antigens of L.
erythrosis, contact the antibodies with
blood samples from a patient, and
check for any antibody binding, wherein
any binding is indicative of the presence
of the microorganism.
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Claim 1. A peptide consisting of the following
amino acid sequence: Ser Thr Ile Phe Leu Glu Ser
Thr His Glu Asp Ile Ser Glu Ala Ser Glu.


Analysis:
For claim 1, the specification discloses how to
make the claimed peptide. Furthermore,
while the only explicitly disclosed use for the
peptide is as a vaccine, which may not be
enabled, the example taken with the state of
the prior art implies a well established utility
of using the peptide to raise antibodies for
using in assays for erythrosis.
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Claim 2.
A vaccine comprising the peptide of
claim 1 and a pharmaceutically acceptable carrier.

With respect to claim 2, the "vaccine" language in
combination with the fact that the only disclosed use
of the compositions is for a vaccine leads to the
conclusion that this claim should be evaluated in
terms of whether the specification teaches how to
make and use the composition as a vaccine. While
the specification provides some guidance regarding
vaccination, it would be reasonable to conclude that
it would require an undue amount of
experimentation to use the composition as a vaccine
in view of the unpredictability in the art and the lack
of working examples
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Claim 3.
A method of inducing an immune response in a
host comprising administering to the host a composition
comprising the peptide of claim 1 and a carrier.

Claim 3 is a broad claim. When read in light
of the specification and the state of the prior
art, it covers methods of producing
antibodies for use in diagnostic assays as
well as vaccination. Thus, claim 3 must be
evaluated as to whether the specification
enables the entire scope of the claim.
Therefore, it would be reasonable to make a
scope of enablement rejection.
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112 1st Paragraph -Written Description

Written Description
 Can
one skilled in the art reasonably conclude the
inventor had possession of the claimed invention at
the time the application was filed.
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Satisfying Written Description

Disclosure of adequate relevant identifying
characteristics
 structure
 physical
and/or chemical characteristics
 functional characteristics which are coupled with a
known or disclosed correlation between function and
structure.
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Claim 1.
Claim 2.

A vaccine comprising an isolated protein comprising
SEQ ID NO:3.
A vaccine comprising a variant of the protein of claim 1
Specification:
 The
specification describes a protein isolated from
liver.
 A working
example shows that the isolated protein
was sequenced and determined to consist of SEQ ID
NO: 3.
 The
isolated protein was characterized as being 65 kD
and having tumor necrosis activity.
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Claim 1. A vaccine comprising an isolated protein
comprising SEQ ID NO:3.
Claim 2. A vaccine comprising a variant of the protein of
claim 1.


The specification states that the invention provides
variants of SEQ ID NO: 3 having one or more amino
acid substitutions, deletions, insertions and/or additions.
No further description of the variants is provided.
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Claim 1: A vaccine comprising an isolated
protein comprising SEQ ID NO: 3.

Analysis:

One member of the genus, SEQ ID NO: 3, is
described by a complete structure.

Relatively little variation among the species
within the genus because each member of the
genus shares SEQ ID NO: 3 as a necessary
common feature.
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Claim 2: A vaccine comprising a variant of the
protein of claim 1.

This is a genus claim.

The specification, states a variant is a protein having one
or more amino acid substitutions, deletions, insertions
and/or additions made to the sequence.

The specification and claim do not indicate what
structural and functional attributes are shared by the
members of the genus and essential to the claimed
invention.
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Claim 2: A vaccine comprising a variant of
the protein of claim 1.

The specification and claim do not place any limit on the
number of amino acid substitutions, deletions, insertions
and/or additions that may be made to SEQ ID NO: 3.

The scope of the claim includes numerous structural
variants.

The genus is highly variant because a significant number
of structural differences between genus members is
permitted.
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Claim 2: A vaccine comprising a variant of
the protein of claim 1.

Structural features that could distinguish
compounds in the genus from others in the protein
class are missing from the disclosure.

No common structural and functional attributes
identify the members of the genus.
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Claim 2: A vaccine comprising a variant of
the protein of claim 1.

Since the disclosure fails to describe the common
attributes or characteristics that identify members of the
genus, and because the genus is highly variant, SEQ ID
NO: 3 alone is insufficient to describe the genus.

One of skill in the art would reasonably conclude that
the disclosure fails to provide a representative number of
species to describe the genus. Thus, applicant was not in
possession of the claimed genus.
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Patentability DeterminationVaccine Art
 Prior Art
 Claim
typically examined as a
composition.
 Composition comprising a deleterious
substance which prevents from using as a
vaccine would not usually be considered a
vaccine.
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Protein vaccine claim
 A vaccine
comprising an isolated protein
comprising SEQ ID NO:1 or a portion
thereof.
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Patentability Considerations-Protein Vaccine
 Anticipation



Scope of the claim is evaluated as broadly as reasonable.
“portion” as recited could possibly read on a single amino acid
unless defined in the specification otherwise.
reads on a protein molecule that inherently has the same
sequence as claimed.
 Obviousness

reference(s) teach or suggest a protein with the sequence as
recited.
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Means to Obviate the Anticipation

Amend claims.

Provide evidence the sequence of the claimed protein is
not the same as the protein of the prior art.

Provide evidence that the reference is non-enabling.
- Composition is prevented from being used as a
vaccine.
- Reference does not enable how to make the claimed
composition.
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Means to obviate obviousness
 Provide
evidence of unexpected results.
 Provide
evidence that the prior art does not
suggest a protein having the specific
sequence as claimed.
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United States Patent and
Trademark Office
Thank You
Christina Chan
Supervisory Primary Examiner
At Unit 1644
Phone: 571-272-0841
E-mail: [email protected]
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