Dolly the Sheep was the first mammal created by cloning of an adult cell. To create her, a nucleus was extracted from a mammary cell of an adult sheep (the nuclear donor). The nucleus was then fused with an egg cell produced by another sheep (the egg donor). This fused egg cell was implanted into the womb of a surrogate ewe, where it successfully developed into the baby lamb, Dolly, a clone of the nuclear donor sheep. The inventors of the process used to create Dolly were granted a patent on the method of cloning mammals from adult cells. However, the U.S. Patent and Trademark Office refused to grant a patent on the cloned animals themselves. The case, In Re Roslin Institute (Edinburgh), was appealed to the Federal Circuit Court of Appeals, which held that the claims to a cloned mammal were not eligible for patenting because the cloned animals are genetically identical to the nuclear donor animal. The Federal Circuit reasoned that the nuclear donor animal is a product of nature, and therefore its clone is unpatentable as a copy of a product of nature.
If Dolly was truly an exact copy of the sheep from whom the nucleus was obtained, the Federal Circuit decision would be less significant. “Products of nature” are not eligible for patent protection under 35 U.S.C. §101. In the case of cloning, the original adult sheep from whom the nucleus was obtained was a naturally occurring organism and was therefore a “product of nature” and not patentable. In addition, if a product as made by an old process is not patentable then the identical product made by a new process is also not patentable. Making the product by the new process would only make the new product patentable if it is different from the old product. Therefore, if Dolly was an exact duplicate of the nuclear donor sheep, then she and other animals like her would also not be patentable. The process of making the cloned animals is patent eligible. However, the cloned animals would not be patentable even though they are made by the new process.
Cloned animals like Dolly, however, are not exactly the same as the animals from whom their nuclear DNA is obtained. There are several differences between the nuclear donor animals and their clones, including phenotypic differences in size, shape, color, and behavior that develop as a result of the environment, differences in the ages of the animals (with the clone being a time delayed version of the nuclear donor animal), and differences in the mitochondrial DNA. The later difference occurs because the mitochondria are located outside of the nucleus. In cloned animals like Dolly, the mitochondria of the clone come from the egg cell and therefore from the egg donor animal, not the nuclear donor. As a result, the cloned animals can be distinguished, at a cellular level, from the nuclear donor animal of which they are a copy.
The Federal Circuit held that these differences between the cloned animal and the nuclear donor animal were not adequate to make the clone patentable because they were not called for in the claims. In its decision, the Court presented the following claim as representative:
155. A live-born clone of a pre-existing, non-embryonic, donor mammal, wherein the mammal is selected from cattle, sheep, pigs, and goats.
The Federal Circuit explained that the use of the word cloned in the claims connotes genetic identity, and any differences in phenotype or mitochondrial DNA are not claimed. The Court further stated that having the same DNA as a donor animal would not make an animal ineligible for a patent, but in this particular case the claims did not call for clones with markedly different characteristics from the nuclear donor animal.
The reasoning applied by the Federal Circuit may be surprising to many patent attorneys. The claim calls for the animal to be a “clone,” which indicates the process by which the animal was made – by cloning. The use of the cloning process results in inherent differences between the cloned animal and the nuclear donor animal. The clone is, therefore, not truly identical to the animal from which it is copied, even if it includes the same nuclear DNA. Therefore, one might expect the use of the word “clone” in the claim to be sufficient to distinguish the animal, as a product of cloning, from a naturally occurring organism and therefore to make the clone patentable.
This decision is particularly significant for the biotech community, since it seems to raise the patentability bar even higher for products which are copies of things which occur in nature. That is, even if a patent claim calls for a product to be made by a particular process, and that process would result in the product being different than in nature, this decision suggests that this may not be enough. The product may still be held unpatentable as a product of nature if the differences are not included in the claim. This decision, therefore, calls into doubt the patentability and validity of claims to artificially created products which are like those that exist in nature, such as recombinantly produced products, if a difference between the natural products and the recombinantly produced products is not stated in the claims. In addition, the Federal Circuit’s decision includes references to cloned animals not being “markedly different” from the animals in nature, suggesting that a certain degree of difference (a “marked” difference) may be required for patentability, though such a requirement is not definitively stated in the decision.
Patent practitioners should take note of this decision when drafting claims to biotech products. If the product is a copy of a product of nature but has inherent differences due to the process by which it is made, at least some of the claims should include limitations directed to these differences. In addition, if the differences are minor and not “marked” there may still be difficulties in achieving patentability, although the applicability of this standard is less clear.