BitLaw

Example 12 (4): Purified Proteins

This example illustrates that changes in physical/chemical structure (claims 2-5) as compared to a product’s natural counterpart can demonstrate markedly different characteristics, whether or not accompanied by changes in biological/pharmacological function or chemical/physical properties.

Background:

Newly discovered Streptomyces arizoneus bacteria produce Antibiotic L, which exhibits antibiotic activity in nature (e.g., it kills other bacterial species in its natural environment). Naturally occurring Antibiotic L is a protein that occurs in the form of hexagonal-pyramidal crystals (each crystal has the shape of a six-sided pyramid) that are stored inside the bacteria. The specification describes several processes that yield Antibiotic L having the same hexagonal-pyramidal crystal form as naturally occurring Antibiotic L. The specification also discloses a process that yields purified Antibiotic L in the form of tetrahedral crystals (each crystal has the shape of a tetrahedron or triangular pyramid). The specification discloses that naturally occurring Antibiotic L has the amino acid sequence of SEQ ID NO: 2, and has a bacillosamine N-glycan on residue 49. In the specification, applicants describe recombinant yeast that are able to synthesize Antibiotic L (naturally occurring yeast cannot synthesize Antibiotic L or bacillosamine). Purified Antibiotic L expressed by these recombinant yeast has a high mannose (instead of a bacillosamine) N-glycan on residue 49, and has lower immunogenicity to humans and a different half-life in vivo than naturally occurring Antibiotic L. The specification defines “purified Antibiotic L” as only being either Antibiotic L in the tetrahedral crystal form or Antibiotic L having a high mannose N- glycan on residue 49.

Applicants disclose substitution modifications of Antibiotic L, e.g., peptides having one or more amino acids substituted with different amino acids relative to SEQ ID NO: 2. No substitution modifications of Antibiotic L are known to occur in nature. Some of the modifications result in altering the function of the peptide, for example by increasing its ability to penetrate the cell membrane of a target organism. The modified peptides have 90% or greater identity to SEQ ID NO: 2.

Claims:

1. Antibiotic L.

2. Purified Antibiotic L.

3. The Antibiotic L of claim 1, which is in a tetrahedral crystal form.

4. The Antibiotic L of claim 1, which is expressed by recombinant yeast.

5. A purified antibiotic comprising an amino acid sequence that has at least 90% identity to SEQ ID NO: 2 and contains at least one substitution modification relative to SEQ ID NO: 2.

Analysis of Claims:

These claims are analyzed for eligibility in accordance with their broadest reasonable interpretation. Because all of the claims are directed to a statutory category, e.g., a composition of matter (Step 1: YES), and are nature-based products (Antibiotic L or a derivative thereof), the markedly different characteristics analysis is used to determine if the nature-based products are exceptions.

Claim 1: Ineligible.

As described in the specification, some Antibiotic L produced by the applicants is in its naturally occurring hexagonal-pyramidal crystal form, while other Antibiotic L is in a non-natural form, e.g., tetrahedral crystals. The claim thus encompasses antibiotic that is identical to the natural antibiotic, and antibiotic that is changed. Because there is no difference in characteristics (structural, functional, or otherwise) between the claimed and naturally occurring antibiotic for at least some of the embodiments encompassed by the claim, the claimed Antibiotic L does not have markedly different characteristics from what exists in nature, and thus is a “product of nature” exception. Accordingly, the claim is directed to an exception (Step 2A: YES). Because the claim does not include any additional features that could add significantly more to the exception (Step 2B: NO), the claim does not qualify as eligible subject matter, and should be rejected under 35 U.S.C. § 101.

Claim 2: Eligible.

Based on the specification’s definition of purified Antibiotic L, the claim is limited to Antibiotic L in the form of tetrahedral crystals or having a high-mannose N-glycan on residue 49. The claim does not encompass naturally occurring Antibiotic L (which forms hexagonal-pyramidal crystals, and has a bacillosamine N-glycan on residue 49). The claimed antibiotic has particular structural/physical characteristics that are different from the naturally occurring antibiotic (e.g., different crystalline form or different N-glycan). The person of ordinary skill in the art would understand that these structural differences may result in the claimed antibiotic having different functional characteristics (e.g., different powder flow behavior or lower immunogenicity and different half-life) than the naturally occurring antibiotic. These differences rise to the level of a marked difference, and thus the claimed antibiotic 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.

Claim 3: Eligible.

The claim is limited to Antibiotic L in the form of tetrahedral crystals, and does not encompass the naturally occurring hexagonal-pyramidal crystals. Although the claimed antibiotic is chemically unchanged from nature, the claimed antibiotic has particular structural/physical characteristics that are different from the naturally occurring antibiotic (e.g., different crystalline form). The person of ordinary skill in the art would understand that these structural differences may result in the claimed antibiotic having different functional characteristics (e.g., powder flow behavior) than the naturally occurring antibiotic. These differences rise to the level of a marked difference, and thus the claimed antibiotic 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.

Claim 4: Eligible.

During examination, a product-by-process claim is not limited to manipulations of the recited steps, but instead is only limited to the structure implied by the steps. In this case, the specification describes that Antibiotic L produced by recombinant yeast has a different structure (high-mannose N- glycan) than the natural antibiotic (bacillosamine N-glycan). The claim is therefore limited to a structurally different Antibiotic L having a high-mannose N-glycan. This structural difference results in a change to the properties of the claimed antibiotic (lower immunogenicity and different half-life than the natural antibiotic). These differences rise to the level of a marked difference, and thus the claimed antibiotic 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.

Claim 5: Eligible.

The claim is limited to peptides in which the amino acid sequence has at least 90% identity to SEQ ID NO: 2, but has been changed to contain at least one non-naturally occurring substitution modification relative to SEQ ID NO: 2. All of the claimed peptides have different structural characteristics (e.g., one or more amino acids have been changed relative to the natural sequence). Some of the claimed peptides may have different functional characteristics, but at least for some conservative modifications there may be no observable functional difference. Because the structural differences between the claimed peptides and their natural counterparts are enough to ensure that the claim is not improperly tying up the future use of naturally occurring Antibiotic L, they rise to the level of a marked difference, and thus the claimed antibiotic 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.