BitLaw

Example 17 (9): Cells

This example illustrates that a man-made product identical to a naturally occurring product does not have markedly different characteristics (claim 1), but that changes in phenotype caused by human manipulation can result in markedly different characteristics (claims 2 and 3). It also demonstrates the application of the “significantly more” analysis to claims directed to a “product of nature” exception (claims 4 and 5).

Background:

Human stem cells are naturally occurring cells that can develop, through a process called differentiation, into many different types of cells, such as cardiac cells, skin cells, and so on. Stem cells have utility in regenerative medicine, which involves repairing diseased tissues or organs. One type of diseased tissue that often needs repair is the heart’s pacemaker, which is formed from pacemaker cells that generate electrical impulses to control heart rate. In nature, pacemaker cells can be identified via a protein called marker P located on the cell surface. The pacemaker cells contain genes that are capable of expressing a protein called marker Z, but in nature these genes are never expressed (there are no naturally occurring pacemaker cells that have marker Z on their surface).

Applicant’s specification discloses differentiating stem cells into pacemaker cells, for use in regenerating damaged heart tissue. Applicant discloses isolating stem cells from human volunteers, and then culturing those cells in a particular growth medium in the presence of growth factor A, at various temperatures. Isolation does not change the cells in any way, but applicant’s culture conditions cause the stem cells to differentiate into pacemaker cells. Some of the man-made pacemaker cells produced by applicant are genetically and phenotypically identical (e.g., express marker P) to naturally occurring pacemaker cells. Other man-made pacemaker cells produced by applicant are genetically identical, but have a different phenotype (e.g., express marker Z and exhibit increased efficiency in utilizing oxygen) than naturally occurring pacemaker cells. Isolation of these man-made cells does not change them in any way.

The increased oxygen utilization efficiency of the pacemaker cells expressing marker Z is advantageous in the regeneration of heart tissue in patients who are recovering from damage to the heart, such as that caused by a myocardial infarction (heart attack). Applicant has discovered that a mixed population of pacemaker cells that is about 10-15% positive for marker Z (i.e., about 10-15% of the cells in the population express marker Z), and about 85-90% positive for marker P (i.e., about 85-90% of the cells in the population express marker P), can be injected into a patient’s heart in order to regenerate a pacemaker in vivo (in a patient’s body). This successful regeneration is possible because the cells interact with each other to affect their growth rates, e.g., the cells expressing marker P grow faster in the mixed population than when they are by themselves. However, a cell population with fewer (or no) cells expressing marker Z is not capable of regenerating a pacemaker, because the cell population is starved of oxygen before it can become established in the patient.

The specification discloses compositions including populations of pacemaker cells in containers, such as flasks and petri dishes, which are routinely and conventionally used in laboratories to hold cells. Also disclosed are compositions including populations of pacemaker cells in biocompatible three-dimensional scaffolds. The specification defines “biocompatible three-dimensional scaffolds” as being three- dimensional structures constructed of naturally occurring materials (such as polysaccharides or proteins) that are unchanged from their natural state, in which they are associated with non-cardiac cells, but that have been removed from their natural environment. The specification specifically excludes cardiac tissue from the definition of “biocompatible three-dimensional scaffolds”. The specification also discloses that compositions including populations of pacemaker cells in the biocompatible three-dimensional scaffolds can be implanted directly into a patient, where they facilitate faster tissue regeneration than when pacemaker cells are implanted by themselves, because the scaffold provides mechanical support for the implanted cells to grow.

Claims:

1. An isolated man-made human pacemaker cell.

2. An isolated man-made human pacemaker cell expressing marker Z.

3. A population of human pacemaker cells, wherein the population is about 10-15% positive for marker Z, and 85-90% positive for marker P.

4. A composition comprising a population of isolated man-made human pacemaker cells in a container.

5. A composition comprising a population of isolated man-made human pacemaker cells in a biocompatible three-dimensional scaffold.

Analysis of Claims:

These claims are analyzed for eligibility in accordance with their broadest reasonable interpretation. All of the claims are directed to a statutory category, e.g., a composition of matter (Step 1: YES).

Claim 1: Ineligible.

Because the claim is a nature-based product, i.e., a cell, the nature-based product is analyzed to determine whether it has markedly different characteristics from any naturally occurring counterpart(s) in their natural state. As described in the specification, some of the man-made cells are identical to what exists in nature (e.g., same genotype and phenotype), while others are phenotypically different from what exists in nature (e.g., express marker Z and have increased oxygen utilization), and these difference arose due to applicant’s efforts. The claim thus encompasses cells that are identical (no difference in characteristics) to naturally occurring cells, and cells that are phenotypically different. Because there is no difference between the claimed and naturally occurring cells for at least some of the embodiments encompassed by the claim, the claimed cells do not have markedly different characteristics, and thus are a “product of nature” exception. In re Roslin Institute (Edinburgh), 750 F.3d 1333, 1338-39 (Fed. Cir. 2014). 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.

The claim is limited to human pacemaker cells that express marker Z, which are nature- based products. No human pacemaker cells expressing marker Z are naturally occurring. As described in the specification, the claimed cells are exact genetic replicas of naturally occurring pacemaker cells, that were produced from naturally occurring stem cells. However, the claimed cells are phenotypically different than natural pacemaker cells, in that they express marker Z and have increased oxygen utilization efficiency. Further, these phenotypic differences were created by applicant’s efforts (e.g., by culturing the stem cells in a particular growth medium in the presence of growth factor A, at various temperatures), and were not the work of nature. These phenotypic differences rise to the level of a marked difference, and accordingly the claimed cell 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 a population of human pacemaker cells, where about 10-15% of the cells express marker Z, and about 85-90% express marker P. Because the claim is a nature-based product, i.e., a combination of cells, the nature-based product (the population) is analyzed to determine whether it has markedly different characteristics from any naturally occurring counterpart(s) in their natural state. As discussed above with respect to claims 1 and 2, the cells expressing marker Z have markedly different characteristics than naturally occurring cardiac pacemaker cells because of their phenotypic differences, but the cells expressing marker P do not have markedly different characteristics because they are identical to naturally occurring pacemaker cells. However, as described in the specification, when these cells are mixed together in the claimed ratio to form the claimed population, the cells interact with each other to affect their growth rates, e.g., the cells expressing marker P grow faster in the mixed population than when they are by themselves. Naturally occurring pacemaker cells do not grow at this rate in their natural state. This difference in biological properties (rate of cell growth) between the claimed cell population and naturally occurring human pacemaker cells rises to the level of a marked difference, and accordingly the claimed population 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: Ineligible.

Because the claim recites a nature-based product, i.e., the population of cells, the nature-based product is analyzed to determine whether it has markedly different characteristics from any naturally occurring counterpart(s) in their natural state. As explained with respect to claim 1, isolated man-made pacemaker cells do not have markedly different characteristics due to their isolation or human manufacture. There is no indication in the specification that placing the cells in a generic container results in the cells having any characteristics (structural, functional, or otherwise) that are different from the naturally occurring cells in their natural state. Thus, the claimed population of cells does not have markedly different characteristics from what occurs in nature, and is a “product of nature” exception. Accordingly, the claim is directed to an exception (Step 2A: YES). Next, the claim as a whole is analyzed to determine whether any element, or combination of elements, is sufficient to ensure that the claim amounts to significantly more than the exception. Although the claim recites a container, use of a container to hold cells is not only well-understood, routine and conventional activity already engaged in by the scientific community, it is also required for growing and using the cells. Additionally, the claim recites the container at such a high level of generality that it merely tells a scientist to use whatever container she wishes to use. Therefore, the claim as a whole adds nothing significantly more to the “product of nature” itself. Thus, the claim does not amount to significantly more than the judicial exception itself (Step 2B: NO). The claim does not qualify as eligible subject matter, and should be rejected under 35 U.S.C. § 101.

Claim 5: Eligible.

Because the claim is a nature-based product, i.e., a combination of cells and a scaffold, the nature-based product (the combination) is analyzed to determine whether it has markedly different characteristics from any naturally occurring counterpart(s) in their natural state. As explained with respect to claim 1, isolated man-made pacemaker cells do not have markedly different characteristics due to their isolation or human manufacture. There is also no indication in the specification that placing the cells into a biocompatible three-dimensional scaffold results in the cells or the scaffold having any characteristics (structural, functional, or otherwise) that are different from the naturally occurring cells or scaffold in their natural state. Thus, the claimed population of cells, and the claimed scaffold, do not have markedly different characteristics from what occurs in nature, and are “product of nature” exceptions. Accordingly, the claim is directed to an exception (Step 2A: YES). Next, the claim as a whole is analyzed to determine whether any element, or combination of elements, is sufficient to ensure that the claim amounts to significantly more than the exception. The recitation of the biocompatible three-dimensional scaffold in combination with the pacemaker cells is not required for growing or using the cells, because the cells can be grown or used in other containers, and is not recited at a high level of generality. The addition of the pacemaker cells to the scaffold confines the claim to a particular useful application of the scaffold (repair of cardiac tissue), because the pacemaker cells are not routinely required for all practical uses of the scaffold. Further, the combination of these elements does more than generally link these two judicial exceptions together; as described in the specification, this combination improves the technology of regenerative medicine, by facilitating faster tissue regeneration than when pacemaker cells are implanted by themselves. Thus, the claim amounts to significantly more than the judicial exception itself (Step 2B: YES), and qualifies as eligible subject matter.