Types%20of%20Vaccines%20and%20Patentability%20Considerations

1
Types of Vaccines andPatentability
Considerations
United States Patent and Trademark Office

• Christina Chan
• Supervisory Primary Examiner
• Art Unit 1644
• Phone [phone]
• E-mail christina.chan_at_uspto.gov

2
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

3
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.

4
Vaccine

• Therapeutic vaccine
• e.g. Therapeutic vaccine for HPV associated
  cervical carcinoma.

5
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.

6
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

7
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)
• Type of immunity induced Produces humoral and
  cell-mediated Produces mainly humoral
  immunity
• 
  immunity
• Reversion tendency May revert to
  virulent form Cannot
  revert to virulent form
• Immunology, Kuby
• 4th Ed. 2000, page 455

8
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

9
Other Types of Vaccines

• Recombinant Vector Vaccines
• e.g. - Vaccinia virus
• Synthetic Peptide Vaccines
• Multivalent Subunit Vaccines
• DNA Vaccines.

10
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)

11
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.

12
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

13
Utility Considerations-DNA vaccine

• Is the utility specific, substantial and
  credible?
• Well established utility.

14
A DNA vaccine comprising an isolated nucleic
acid molecule encoding a protein comprising the
amino acid sequence of SEQ ID NO1.

• 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.

15
A DNA vaccine comprising an isolated nucleic acid
molecule encoding a protein comprising the amino
acid sequence of SEQ ID NO1.

• 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.

16
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.

17
A DNA vaccine comprising an isolated nucleic acid
molecule encoding a protein having the amino acid
sequence of SEQ ID NO1.

• 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.

18
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.

19
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.

20
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

21
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.

22
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.

23
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.

24
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.

25
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

26
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.

27
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.

28
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.

29
Claim 1. A vaccine comprising an isolated
protein comprising SEQ ID
NO3. Claim 2. 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.

30
Claim 1. A vaccine comprising an isolated
protein comprising SEQ ID
NO3.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.

31
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.

32
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.

33
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.

34
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.

35
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.

36
Patentability Determination-Vaccine 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.

37
Protein vaccine claim

• A vaccine comprising an isolated protein
  comprising SEQ ID NO1 or a portion thereof.

38
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.

39
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.

40
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.

41
United States Patent and Trademark Office

• Thank You
• Christina Chan
• Supervisory Primary Examiner
• At Unit 1644
• Phone [phone]
• E-mail christina.chan_at_uspto.gov