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Types of Vaccines and

Patentability Considerations

Christina Chan

Supervisory Primary Examiner

Art Unit 1644

Phone: 571-272-0841

E-mail: christina.chan@uspto.gov

United States Patent andUnited States Patent andTrademark OfficeTrademark Office

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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, Kuby5th 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 vaccinee.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)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, Kuby4th Ed. 2000, page 455

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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: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.

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.

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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. A vaccine comprising an isolated protein comprising

SEQ ID NO:3. 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.

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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 Determination-Vaccine Art

Prior ArtClaim 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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Thank You

Christina Chan

Supervisory Primary Examiner

At Unit 1644

Phone: 571-272-0841

E-mail: christina.chan@uspto.gov

United States Patent andUnited States Patent and Trademark Office Trademark Office