Patenting Stem Cells in View of the USPTO's New Interim Guidance

Late last year, the USPTO issued its modified and revised 2014 Interim Guidance on Patent Subject Matter Eligibility (Interim Guidance) to assist patent examiners and the public in determining if a claim presented for examination is patent-eligible in view of recent U.S. Supreme Court decisions, namely Alice Corp., Myriad, and Mayo. In addition to streamlining the analysis of patent claims directed to any one of the judicial exceptions to patent-eligibility (abstract ideas, laws of nature and physical phenomena), the USPTO provided illustrative examples to be used in combination with the Interim Guidance. One such example discussed the patent-eligibility of claims directed to stem cells or regenerative medicine. Fortunately for these industries, application of the Interim Guidance as discussed in the example finds that many stem cell technologies are patent-eligible.

General Principles of the Interim Guidance

Prior to analyzing patent-eligibility, the claim is interpreted consistent with its broadest reasonable interpretation. After construing the claims, a two-step analysis is applied. The first step asks if the subject matter of the claim is related broadly to patentable subject matter, i.e., does the claim relate to a process, machine or a composition of matter? (Step 1 of the two-step analysis.) If it does not, then the claim is not patent-eligible.

If the answer is yes (and most claimed inventions do relate to one of these statutory classes), then the claim is analyzed to determine if it relates in whole or in part to a judicial exception to patent-eligibility. (Step 2A of the two-step analysis). If the claim does not relate in whole or in part to a judicial exception, then the claim is patent-eligible. If the claim does relate in whole or in part to a judicial exception, then the claim is analyzed for additional elements that amount to something “significantly more” than the judicial exception itself (Step 2B of the two-step analysis).

The analysis only proceeds to step 2B if the claim is directed to the exception. To answer this question, the USPTO compares the claimed subject matter to its natural counterpart to determine if there is a “markedly different characteristic” or a structural or functional difference between the claimed product and its natural counterpart. Exemplary differences include a change in biological or pharmacological functions or activities, chemical or physical properties, changes in phenotype, or changes in structure and form, whether chemical, genetic or physical. Importantly, the Interim Guidance indicates that a product that is purified or isolated will be eligible when there is a resultant change in characteristics sufficient to show a marked difference from the natural counterpart. For claims related to a single product of nature, once a markedly different characteristic is shown, no further analysis is necessary.

Stem Cells as a Nature-Based Product

Example 9 of the USPTO’s illustrative examples accompanying its Interim Guidance lists 5 claims related to stem cell inventions. The facts accompanying Example 9 note that the claimed cells are the differentiated product of stem cells, cultured under conditions to provide cells that uniquely express marker Z. Natural counterpart human pacemaker cells express marker P, but not marker Z. The cells expressing marker Z have unique phenotypic characteristics – they exhibit increased efficiency in utilizing oxygen. A mixed population of cells expressing marker P and Z can be successfully used to regenerate cardiac tissue. This property of the mixed population is attributed to the cells expressing marker Z. A population of cells having less than 10% cells expressing marker Z are not capable of regenerating cardiac tissue.

The cells can be combined with “biocompatible, three-dimensional scaffolds” constructed from natural products that are unchanged from the products in their natural state. The scaffold, when combined with the cells, allows the cells to be directly implanted into a patient where they facilitate faster tissue regeneration than when the cells are implanted by themselves.

Five hypothetical claims are provided as examples:

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, where 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.

Claims 1 and 2

Claims 1 are 2 are the broadest claims, each relating to an isolated cell product. Some of the man-made cells are identical to the natural counterpart human pacemaker cells in that they have the same phenotype and genotype of the naturally occurring cells. Because the cell of claim 1 does not possess “markedly different” characteristics from a naturally occurring human pacemaker cell, it fails step 2A of the Interim Guidance analysis. The claim is then analyzed under step 2B to determine if the claim includes any additional features that could add significantly more to the judicial exception. The facts of the example do not provide any additional features. The answer to step 2B in this example therefore is no — claim 1 does not define a patent-eligible invention.

In contrast, claim 2 does define a patent-eligible invention because there is no natural counterpart cell to the cell expressing marker Z. According to the background facts describing the claims, a cell expressing marker Z has increased oxygen utilization efficiency. This phenotypic difference is the result of culturing the cell under certain conditions. According to the example, these difference rise to the level of “markedly different” characteristics, and the claim thus is not directed to a judicial exception to patent-eligible subject matter. Claim 2 therefore is patent-eligible, and an analysis under step 2B is not necessary.

Claim 3

Claim 3 relates to a population of human pacemaker cells that are not described as “man-made.” From the analysis of claim 2, it is known that natural human pacemaker cells do express marker Z and that the combined population of cells possess a functional difference from naturally occurring cells. Claim 3 therefore is patent-eligible, and an analysis under step 2B is not necessary.

Claim 4

Claim 4 describes an invention that is a combination of a cell that does not possess a markedly difference from a naturally occurring cells and a generic container. Thus, under step 2A, the claim is directed to a judicial exception to patent-eligible subject matter. The analysis then proceeds to step 2B, to determine if the claim recites “something more” that the product of nature itself. The addition of the general purpose container, determined to be well-understood, routine and conventional by those in the field to grow and culture cells. Thus, the claim does not describe patent-eligible subject matter.

Claim 5

Claim 5 is directed to a combination of natural products – a population of isolated cells and a biocompatible scaffold. Thus, the claim is analyzed to determine if the combination has markedly different characteristics from any naturally occurring counterpart(s) in their natural state. There is no indication that the claimed combination has any structural or functional difference from the individual cells or scaffold that occurs in nature. Thus, the claimed combination is directed to a judicial exception and the analysis then moves to determining if the claimed combination amounts to something “significantly more” than the exception. The biocompatible scaffold is not required for growing or using the cells, and the use of the scaffold confines the cells to one useful application. The combination also improves regenerative medicine technology by facilitating faster tissue regeneration when implanted in patients. Thus, the claimed combination is significantly more than the judicial exception itself and is patent-eligible.

Patenting Stem Cell Technologies in the U.S.

Example 9 of the Interim Guidance highlights that nature-based products are patent-eligible if they possess any characteristics (structural, functional or otherwise) that are different from their natural counterparts. As can be seen from the comparison of claims 1 and 2 above, the mere fact that the cell is isolated from nature and described as man-made is insufficient to render the claim patent-eligible. An isolated cell that possesses a markedly different characteristic – such as the increase oxygen utilization efficiency of claim 2 – is patent-eligible without further analysis.

Claim 4 of the example also highlights that merely combining a nature-based product with a non-naturally occurring product such as a container does not make a claim patent-eligible if the claimed combination does not possess markedly different characteristics or “something more” than the judicial exception itself. However, when the combination confines the nature based product to a particular useful combination (claim 5) or the combination possesses functional or structural differences from the individual elements as they exist in nature (claim 3), then the claim is patent-eligible.

Patent applicants must now consider and articulate how claimed cells and compositions containing cells, such as isolated stem cells, are markedly different in structure, function or otherwise, to naturally occurring cells. As set forth in the Interim Guidance merely adding a general purpose element will not by itself turn an ineligible claim into an eligible claim.

Example 9 in combination with the Interim Guidance provides applicants with a good roadmap for navigating patent-eligibility in today’s legal environment.