BitLaw

Example 28: Vaccines

This example illustrates the application of the markedly different characteristics and significantly more analyses to claims reciting hypothetical nature-based products. It also illustrates the importance of applying the broadest reasonable interpretation in the eligibility analysis, and how that interpretation assists in the identification of appropriate naturally occurring counterparts of claimed nature-based products. Hypothetical claims 1, 2 and 4-6 are eligible in Step 2A, because the claimed nature-based products have markedly different characteristics from what exists in nature. Hypothetical claim 3 is ineligible, because the claimed nature-based product lacks markedly different characteristics from what exists in nature, and the claim fails to amount to significantly more than the exceptions. Hypothetical claim 7 is eligible in Step 2B, because although the claim is directed to an exception, it recites a particular and unconventional device that amounts to significantly more than the exception.

Background

Applicant discloses an influenza A viral strain, which was named the “Pigeon flu” because it was discovered in pigeons. Applicant filed an application disclosing several types of Pigeon flu vaccines, and evaluating their functional characteristics (such as immunogenicity) in terms of their seroprotection rate, i.e., the percentage of vaccinated patients who developed immunity to the Pigeon flu. The disclosed vaccines include:

• Vaccines comprising “live attenuated Pigeon flu virus”, which the specification defines as a live mutant virus that has been attenuated so that it has at least one mutation (i.e., a change in the nucleotide sequence) of its polymerase gene, which reduces its virulence as compared to naturally occurring Pigeon flu virus. No mutations of this polymerase gene are known to occur in nature. Applicant created this mutant attenuated virus by isolating Pigeon flu virus from infected pigeons, and passaging the isolated virus through a cell culture at least 50 times until the desired mutation occurred. The live attenuated Pigeon flu virus is safe (unable to cause disease in pigeons or other test animals) and strongly immunogenic, e.g., it has a high seroprotection rate of about 85%.

• Vaccines comprising “inactivated Pigeon flu virus”, which the specification defines as a dead virus that is formalin-inactivated, i.e., the naturally occurring Pigeon flu virus was contacted with a chemical solution called formalin that causes structural changes to the virus (e.g., it chemically modifies the viral nucleic acids in a manner that does not occur in nature) so that it can no longer reproduce. Because the inactivated virus can no longer replicate, it is unable to cause disease in pigeons or other test animals, but it is still strongly immunogenic, e.g., it has a high seroprotection rate of about 75%.

• Vaccines comprising Peptide F (a naturally occurring peptide isolated from the Pigeon flu virus) either alone or mixed with a pharmaceutically acceptable carrier such as water. Prior to applicant’s invention, and at the time of filing the application, water was routinely and conventionally used as a carrier for peptide vaccines. Isolation does not change any structural or functional characteristics of Peptide F. Applicant discloses vaccines where the suitable pharmaceutically acceptable carrier is selected from a group consisting of a cream, emulsion, gel, liposome, nanoparticle, or ointment. Applicant discloses that although the carriers in this group comprise naturally occurring components (such as water and oil), when the components are assembled into the carrier form, the carrier has changed structural and physical characteristics that distinguish it from the closest counterpart in nature. E.g., a pharmaceutically acceptable cream comprising water and vegetable oil has a form (a semi- solid homogeneous emulsion) that is structurally and physically distinct from the water and oil in nature. These vaccines are weakly immunogenic, e.g., they have a low seroprotection rate of about 30%, meaning that many people who are vaccinated with these vaccines will not develop immunity to the Pigeon flu.

• Vaccines comprising Peptide F mixed with aluminum salt adjuvants (a well-known class of adjuvants) such as aluminum phosphate (AlPO4). While many of these adjuvants including aluminum phosphate are naturally occurring, none of them occur together with Peptide F in nature. Adjuvants are commonly added to vaccines in order to improve their functional characteristics, e.g., by increasing the strength of the immune response that the vaccines produce (immunogenicity). The amount of adjuvant sufficient to increase a vaccine’s immunogenicity to a level high enough to effectively vaccinate a typical patient is called the “immuno-effective amount”, and those skilled in the art understand that this amount may vary depending on the particular adjuvant and formulation selected. Adjuvants can increase immunogenicity in several ways, such as by slowing the release of Peptide F to tissue around the injection site, and/or by improving the delivery of Peptide F to the patient’s lymph nodes. On their own or combined with water or other common carriers, Peptide F induces only a weak protective immune response to Pigeon flu virus (seroprotection rate of 30%), and the adjuvants do not induce any protective immune response to Pigeon flu virus (seroprotection rate of 0%). When immuno-effective amounts of the disclosed adjuvants are combined with Peptide F, however, the combined vaccine induces a strong immune response to Pigeon flu virus (seroprotection rate of 80%).

Applicant also discloses vaccine delivery devices comprising coated microneedle arrays for delivery of a vaccine comprising Peptide F. Prior to applicant’s invention, and at the time the application was filed, it was routine and conventional in the field to use syringes, but not coated microneedle arrays, for vaccine delivery. A pre-filled syringe is a tube that has been loaded with a vaccine dose prior to distribution of the vaccine to health professionals. The syringe can be fitted with a hollow needle about 5/8” to 1.5” long to administer the vaccine subcutaneously or intramuscularly. A coated microneedle array comprises a plurality of very small solid needles (e.g., less than 0.05” long) that are coated with a vaccine formulation, which is placed against a patient’s skin to administer the vaccine into the skin (transcutaneously). Because the microneedles are very small, administration of a vaccine with a microneedle array is virtually painless.

Claims

A vaccine comprising live attenuated Pigeon flu virus.

A vaccine comprising inactivated Pigeon flu virus.

A vaccine comprising:

Peptide F; and
a pharmaceutically acceptable carrier.

A vaccine comprising:

Peptide F; and
a pharmaceutically acceptable carrier selected from the group consisting of a cream, emulsion, gel, liposome, nanoparticle, or ointment.

A vaccine comprising:

Peptide F; and
an immuno-effective amount of an aluminum salt adjuvant.

A vaccine comprising:

Peptide F; and
an immuno-effective amount of an aluminum salt adjuvant; and
a pharmaceutically acceptable carrier.

A vaccine delivery device comprising a microneedle array that is coated with a vaccine comprising Peptide F.

Analysis

Claim 1: Eligible.

The claim recites a vaccine comprising live attenuated Pigeon flu virus. Based on the plain meaning of “vaccine”, and the specification’s definition of “live attenuated Pigeon flu virus”, the broadest reasonable interpretation of the claim is live mutant Pigeon flu virus that has been attenuated so that it has at least one mutation (i.e., a change in its nucleotide sequence) that reduces its virulence as compared to naturally occurring Pigeon flu virus, in an amount sufficient to produce an immunogenic response in a typical patient. Because viruses are composed of matter, the claim is directed to a statutory category, e.g., a composition of matter (Step 1: YES).

The claim is then analyzed to determine whether it is directed to any judicial exception. The recited live attenuated virus is a nature-based product that must be compared to its naturally occurring counterpart to determine if it has markedly different characteristics than the counterpart. Here, the closest natural counterpart is the naturally occurring Pigeon flu virus from which the live attenuated virus was mutated. When the live attenuated virus is compared to this counterpart, the comparison indicates that the live attenuated virus has a different structural characteristic (the nucleotide sequence of its polymerase gene was changed due to the mutation), which has resulted in the live attenuated virus having a different functional characteristic (reduced virulence). No mutations of this gene are known to occur in nature. Thus, under the holding in Myriad, this structural difference is a markedly different characteristic, because it causes the claimed virus to have a nucleotide sequence that is different from anything found in nature. Association for Molecular Pathology v. Myriad Genetics, Inc., 133 S. Ct. 2107, 2119 (2013). While in other fact patterns, a functional change may be enough by itself to confer eligibility, for this claim the functional change is a result of the structural change and thus is inseparable from it. Because the live attenuated virus has markedly different characteristics from what exists in nature, it is not a “product of nature” exception. Thus, the claim is not directed to an exception (Step 2A: NO), and qualifies as eligible subject matter.

Note that because the analysis of this claim ends at Step 2A, the Step 2B analysis is not performed. Thus, the examiner would not need to evaluate the significantly more considerations for this claim.

If the examiner believes that the record would benefit from clarification, remarks could be added to an Office action or reasons for allowance, indicating that the claim is not directed to any judicial exception.

Claim 2: Eligible.

The claim recites a vaccine comprising inactivated Pigeon flu virus. Based on the plain meaning of “vaccine”, and the specification’s definition of “inactivated Pigeon flu virus”, the broadest reasonable interpretation of the claim is dead Pigeon flu virus that has been structurally altered by contacting it with formalin so that its nucleic acids are chemically modified in a manner that does not occur in nature and it can no longer reproduce, in an amount sufficient to produce an immunogenic response in a typical patient. Because viruses are composed of matter, the claim is directed to a statutory category, e.g., a composition of matter (Step 1: YES).

The claim is then analyzed to determine whether it is directed to any judicial exception. The recited inactivated virus is a nature-based product that must be compared to its naturally occurring counterpart to determine if it has markedly different characteristics than the counterpart. Here, the closest natural counterpart is the naturally occurring Pigeon flu virus. When the inactivated virus is compared to this counterpart, the comparison indicates that the inactivated virus has a different structural characteristic (its exposure to formalin has chemically modified its nucleic acids in a manner that does not occur in nature), which has resulted in the inactivated virus having different functional characteristics (inability to replicate or cause disease). Like the Chakrabarty bacterium, which had markedly different characteristics “due to the additional plasmids and resultant ‘capacity for degrading oil,’” Myriad, 133 S. Ct. at 2117, the inactivated virus has markedly different characteristics, due to the non-natural chemical modification of its nucleic acids and the resultant change in the virus’s ability to replicate or cause disease. While in other fact patterns, a functional change may be enough by itself to confer eligibility, for this claim the functional change is a result of the structural change and thus is inseparable from it. Because the inactivated virus has markedly different characteristics from what exists in nature, it is not a “product of nature” exception. Thus, the claim is not directed to an exception (Step 2A: NO), and qualifies as eligible subject matter.

Note that because the analysis of this claim ends at Step 2A, the Step 2B analysis is not performed. Thus, the examiner would not need to evaluate the significantly more considerations for this claim. If the examiner believes that the record would benefit from clarification, remarks could be added to an Office action or reasons for allowance, indicating that the claim is not directed to any judicial exception.

Claim 3: Ineligible.

The claim recites a vaccine comprising Peptide F and a pharmaceutically acceptable carrier. Based on the plain meaning of “vaccine” and “pharmaceutically acceptable carrier”, the broadest reasonable interpretation (BRI) of the claim is a sufficient amount of Peptide F to produce an immunogenic response in a typical patient, which is mixed with a pharmaceutically sufficient amount of a carrier such as water. Thus, one embodiment within the BRI is a mixture of Peptide F and water. Because the peptide and carrier are composed of matter, the claim is directed to a statutory category, e.g., a composition of matter (Step 1: YES).

The claim is then analyzed to determine whether it is directed to any judicial exception. The recited mixture of Peptide F and water is a nature-based product that must be compared to its closest naturally occurring counterpart to determine if it has markedly different characteristics than the counterpart. Because Peptide F and water do not occur together in nature, there is no naturally occurring counterpart mixture for comparison, and so the claimed mixture is compared to its naturally occurring components, i.e., Peptide F, and water. Peptide F is naturally occurring, and water is naturally occurring, so neither would be eligible as claimed on their own. While the mixture of these two naturally occurring components is novel and does not occur in nature, there is no indication that mixing these components changes the structure, function, or other properties of the peptide or water. For example, the claim encompasses a mixture where the peptide is heterogeneously dispersed in the water, but such heterogeneous mixing does not change the structure, function, or other properties of the peptide or the water in any marked way. Instead, the peptide retains its naturally occurring structure and function, and is merely dispersed in the water, which also retains its naturally occurring structure and function. Thus, for at least one embodiment within the broadest reasonable interpretation, the claimed mixture as a whole does not display markedly different characteristics compared to the naturally occurring counterparts. Accordingly, each component (the peptide and the carrier) is a “product of nature” exception, and the claim is directed to at least one exception (Step 2A: YES).

Next, the claim as a whole is analyzed to determine whether any additional element, or combination of elements, is sufficient to ensure that the claim amounts to significantly more than the exceptions. Because the component elements (the peptide and carrier “product of nature” exceptions) do not occur together in nature and are not markedly changed by their combination into a mixture, each is considered as an additional element to the other. This consideration provides an opportunity to explore whether this combination of “products of nature” amounts to significantly more than the products themselves. As discussed above, mixing the peptide with a carrier such as water does not markedly change the characteristics of either component, because each component continues to have the same properties in the mixture as it had alone. In addition, using a carrier in a peptide vaccine was well-understood, routine & conventional prior to applicant’s invention and at the time of filing the application, so the mixing of the peptide and carrier, when recited at this high level of generality, does not meaningfully limit the claim. Thus, the claim as a whole does not amount to significantly more than each “product of nature” by itself (Step 2B: NO). The claim does not qualify as eligible subject matter.

A rejection of claim 3 should identify the exceptions by pointing to the nature-based products in the claim (the peptide and carrier) and explaining why they lack markedly different characteristics from their naturally occurring counterparts, e.g., because there are no changes in structure, function, or other characteristics. The rejection should also explain that combining the peptide and carrier does not amount to significantly more than the exceptions, because their combination is well-understood, routine and conventional in the field.

If the examiner believes that it would be helpful to cite an analogous court decision, the rejection could include an explanation of how the claimed mixture is like the novel bacterial mixture of Funk Brothers, which was held ineligible because each species of bacteria in the mixture (like each component in the peptide-carrier mixture) continued to have “the same effect it always had”, i.e., it lacked markedly different characteristics. Funk Brothers Seed Co. v. Kalo Inoculant Co., 333 U.S. 127, 131 (1948), discussed in Myriad Genetics, 133 S. Ct. at 2117 (explaining that the bacterial mixture of Funk Brothers “was not patent eligible because the patent holder did not alter the bacteria in any way”).

Claim 4: Eligible.

The claim recites a vaccine comprising Peptide F in a pharmaceutically acceptable carrier selected from the group consisting of a cream, emulsion, gel, liposome, nanoparticle, or ointment. Based on the plain meaning of “vaccine” and “pharmaceutically acceptable carrier”, the broadest reasonable interpretation (BRI) of the claim is a sufficient amount of Peptide F to produce an immunogenic response in a typical patient, which is mixed with a sufficient amount of other substances to produce a carrier form suitable for administration to a patient. The BRI thus encompasses, for example, a vaccine comprising Peptide F in a carrier that is a cream. Because the plain meaning of a “cream” in the pharmaceutical arts is a semi-solid homogeneous emulsion comprising water and oil, the recitation of a cream necessarily requires (i) the presence of water and an oil (such as naturally occurring cottonseed oil) in addition to Peptide F, and (ii) that the water and oil be structurally arranged into a homogenous emulsion to produce a semi-solid form. Thus, one embodiment within the BRI is an emulsion comprising Peptide F mixed with small uniform droplets of cottonseed oil that are homogenously dispersed in water. Because the peptide and the carrier are composed of matter, the claim is directed to a statutory category, e.g., a composition of matter (Step 1: YES).

The claim is then analyzed to determine whether it is directed to any judicial exception. The claimed cream containing Peptide F, cottonseed oil, and water is a nature-based product that must be compared to its closest naturally occurring counterpart to determine if it has markedly different characteristics than the counterpart. Here, all three substances (the peptide, cottonseed oil, and water) do not occur together in nature, so there is no naturally occurring counterpart mixture for comparison. The mixture is therefore compared to its naturally occurring components, i.e., Peptide F, cottonseed oil, and water. The claimed cream has different structural and physical characteristics than its naturally occurring components, for example the oil droplets are small, uniform in size, and homogenously dispersed in the water, which causes the resultant cream to have a semi-solid and non-flowable form at room temperature as compared to the oil and water, which are both flowable liquids at room temperature in nature. Because the oil and water are emulsified, the cream will also adhere to a patient’s skin or mucous membranes much longer than oil or water in their natural non- emulsified form, thus permitting a sufficient amount of peptide to transfer from the cream into the patient’s tissues where it will then stimulate an immune response. In contrast, the oil or water, if used in their natural state, would simply slide off the patient’s skin after a short time. The cream’s changed form and adherence are marked differences in structural and physical characteristics as compared to the natural counterparts, and therefore the cream is not a “product of nature” exception. Thus, the claim is not directed to an exception (Step 2A: NO), and qualifies as eligible subject matter.

Note that because the analysis of this claim ends at Step 2A, the Step 2B analysis is not performed. Thus, the examiner would not need to evaluate the significantly more considerations for this claim. If the examiner believes that the record would benefit from clarification, remarks could be added to an Office action or reasons for allowance, indicating that the claim is not directed to any judicial exception.

Practice Note: The BRI of claim 4 also encompasses cream embodiments in which the oil is a non- naturally occurring oil, or is a naturally occurring oil other than cottonseed oil, or in which the homogenous emulsion is a water-in-oil emulsion instead of an oil-in-water emulsion, as well as embodiments in which the carrier is something other than a cream, e.g., a liposome or nanoparticle carrier. If the examiner were to analyze such embodiments for markedly different characteristics, the analysis may differ slightly due to the choice of different counterparts, but the same result of eligibility would be achieved because in every embodiment, the plain meaning of each carrier recited in the claim requires that the carrier have structural and physical characteristics that distinguish it from the closest counterpart in nature.

Claim 5: Eligible.

The claim recites a vaccine comprising Peptide F and an immuno-effective amount of an aluminum salt adjuvant. Based on the plain meaning of “vaccine” and “immuno-effective amount”, the broadest reasonable interpretation (BRI) of the claim is a mixture of (i) a sufficient amount of Peptide F to produce an immunogenic response in a typical patient, and (ii) a sufficient amount of an aluminum salt adjuvant (e.g., aluminum phosphate; AlPO4) to increase the vaccine’s immunogenicity (measured here by seroprotection rate) to a level high enough to effectively vaccinate a typical patient. Thus, one embodiment within the BRI is a mixture of Peptide F with a sufficient amount of aluminum phosphate to increase the vaccine’s immunogenicity. Because the peptide and adjuvant are composed of matter, the claim is directed to a statutory category, e.g., a composition of matter (Step 1: YES).

The claim is then analyzed to determine whether it is directed to any judicial exception. The claimed mixture of Peptide F and aluminum phosphate is a nature-based product that must be compared to its closest naturally occurring counterpart to determine if it has markedly different characteristics than the counterpart. Because Peptide F and aluminum phosphate do not occur together in nature, there is no naturally occurring counterpart mixture for comparison, and so the claimed mixture is compared to its naturally occurring components, i.e., Peptide F, and the adjuvant (e.g., aluminum phosphate). There is no indication that mixing these components changes the structure of the peptide or aluminum phosphate. However, the mixture has a changed functional property, in that the immunogenicity of the mixture is different (higher) than the mere “sum” of the immunogenicity of the individual components. In other words, the peptide by itself has poor immunogenicity (30% seroprotection rate) and the adjuvant by itself has no immunogenicity (0% seroprotection rate) with respect to Pigeon flu virus, but when combined, the resultant mixture has a greatly enhanced immunogenicity (80% seroprotection rate) with respect to Pigeon flu virus. The mixture’s changed immunogenicity is a marked difference in functional characteristics as compared to the natural counterparts, and therefore the mixture is not a “product of nature” exception. Thus, the claim is not directed to an exception (Step 2A: NO), and qualifies as eligible subject matter.

Note that because the analysis of this claim ends at Step 2A, the Step 2B analysis is not performed. Thus, the examiner would not need to evaluate the significantly more considerations for this claim. If the examiner believes that the record would benefit from clarification, remarks could be added to an Office action or reasons for allowance, indicating that the claim is not directed to any judicial exception.

Practice Note: The BRI of claim 5 also encompasses embodiments in which the adjuvant is a non- naturally occurring aluminum salt, or is a naturally occurring aluminum salt other than aluminum phosphate. If the examiner were to analyze such an embodiment for markedly different characteristics, the analysis may differ slightly due to the choice of different counterparts, but the same result of eligibility would be achieved because in every embodiment, the immuno-effective amount of the adjuvant will result in the claimed mixture exhibiting the same marked difference in immunogenicity described in the preceding analysis.

Claim 6: Eligible.

The claim recites a vaccine comprising Peptide F, an immuno-effective amount of an aluminum salt adjuvant, and a pharmaceutically acceptable carrier. Based on the plain meaning of “vaccine”, “immuno-effective amount”, and “pharmaceutically acceptable carrier”, the broadest reasonable interpretation of the claim is a mixture of (i) a sufficient amount of Peptide F to produce an immunogenic response in a typical patient, (ii) a sufficient amount of an aluminum salt adjuvant (e.g., aluminum phosphate; AlPO4) to increase the vaccine’s immunogenicity (measured here by seroprotection rate) to a level high enough to effectively vaccinate a typical patient, and (iii) a pharmaceutically sufficient amount of a carrier such as water. Thus, one embodiment within the BRI is a mixture of Peptide F, a sufficient amount of aluminum phosphate to increase the vaccine’s immunogenicity, and water. Because the peptide, adjuvant, and carrier are composed of matter, the claim is directed to a statutory category, e.g., a composition of matter (Step 1: YES).

The claim is then analyzed to determine whether it is directed to any judicial exception. The claimed mixture of Peptide F, aluminum phosphate, and water is a nature-based product that must be compared to its closest naturally occurring counterpart to determine if it has markedly different characteristics than the counterpart. Here, all three substances (the peptide, aluminum phosphate, and water) do not occur together in nature, so there is no naturally occurring counterpart mixture for comparison. However, aluminum phosphate does occur naturally in combination with water (e.g., in soil). Accordingly, the closest naturally occurring counterparts to which the claimed mixture is compared are Peptide F, and the naturally occurring water/aluminum phosphate combination. There is no indication that mixing the peptide with the water/aluminum phosphate combination changes the structure of either component, but the mixture does have a changed functional property, in that the immunogenicity of the mixture is different (higher) than the mere “sum” of the immunogenicity of the individual components. In other words, the peptide by itself has poor immunogenicity (30% seroprotection rate), and the water/aluminum phosphate combination by itself has no immunogenicity (0% seroprotection rate) with respect to Pigeon flu virus, but when combined, the resultant mixture has a greatly enhanced immunogenicity (80% seroprotection rate) with respect to Pigeon flu virus. The mixture’s changed immunogenicity is a marked difference in functional characteristics as compared to the natural counterparts, and therefore the mixture is not a “product of nature” exception. Thus, the claim is not directed to an exception (Step 2A: NO), and qualifies as eligible subject matter.

Note that because the analysis of this claim ends at Step 2A, the Step 2B analysis is not performed. Thus, the examiner would not need to evaluate the significantly more considerations for this claim. If the examiner believes that the record would benefit from clarification, remarks could be added to an Office action or reasons for allowance, indicating that the claim is not directed to any judicial exception.

Practice Note: The BRI of claim 6 also encompasses embodiments in which the adjuvant is a non- naturally occurring aluminum salt, or is a naturally occurring aluminum salt other than aluminum phosphate, and embodiments in which the carrier is something other than water. If the examiner were to analyze such an embodiment for markedly different characteristics, the analysis may differ slightly due to the choice of different counterparts, but the same result of eligibility would be achieved because in every embodiment, the immuno-effective amount of the adjuvant will result in the claimed mixture exhibiting the same marked difference in immunogenicity described in the preceding analysis.

Claim 7: Eligible.

The claim recites a vaccine delivery device comprising a microneedle array that is coated with a vaccine comprising Peptide F. Based on the plain meaning of “microneedle array” and “vaccine”, the broadest reasonable interpretation (BRI) of the claim is an array of small solid needles coated with a sufficient amount of Peptide F to produce an immunogenic response in a typical patient. Thus, one embodiment within the BRI is an array of small solid needles (the microneedle array) coated with Peptide F. The microneedle array is a manufacture and the peptide is composed of matter; thus, the claim is directed to at least one statutory category, e.g., a manufacture and/or a composition of matter (Step 1: YES).

The claim is then analyzed to determine whether it is directed to any judicial exception. The microneedle array is not a nature-based product, but the Peptide F is a nature-based product that must be compared to its closest naturally occurring counterpart (naturally occurring Peptide F) to determine if it has markedly different characteristics than the counterpart in its natural state as part of the virus. There is no indication in the specification that isolation changes any structural or functional characteristics of Peptide F, or that coating the needles in the array with Peptide F results in the peptide having any characteristics (structural, functional, or otherwise) that are different from the naturally occurring peptide in its natural state. Thus, the claimed peptide does not display markedly different characteristics compared to the naturally occurring counterpart. Accordingly, the peptide is a “product of nature” exception, and the claim is directed to at least one exception (Step 2A: YES).

Next, the claim as a whole is analyzed to determine whether any additional element, or combination of elements, is sufficient to ensure that the claim amounts to significantly more than the exception. Besides the exception, the claim recites an additional element of the microneedle array, which is coated with the peptide. Prior to applicant’s invention, and at the time the application was filed, coated microneedle arrays were known to most scientists in the field, but were not routinely or conventionally used to administer vaccines. The conventional delivery device was a syringe that was routinely pre-filled with the vaccine. Thus, the claim’s recitation of a microneedle array coated with the peptide is an application of the exception with a particular manufacture that is not a conventional delivery device, and thus is more than a mere instruction to “apply” the peptide (the exception) using a well-understood, routine or conventional device in the field. It is an unconventional limitation that confines the exception to a particular useful application of the exception. Thus, the recitation of the coated microneedle array yields a claim as a whole that amounts to significantly more than the “product of nature” exception itself (Step 2B: YES). The claim is eligible.

If the examiner believes that the record would benefit from clarification, remarks could be added to an Office action or reasons for allowance indicating that the peptide is a “product of nature” exception because it lacks markedly different characteristics from its naturally occurring counterpart, e.g., because there are no changes in structure, function, or other characteristics. However, the claim is eligible because it recites a particular, unconventional limitation (the coated microneedle array) that confines the exception to a particular useful application, and that is more than a mere instruction to “apply” the exception using a well-understood, routine or conventional device in the field.