Patent aspects of human cloning in the US

PATENT ASPECTS OF HUMAN CLONING IN THE US

by William S. Feiler

Ever since James Watson and Francis Crick elucidated the structure of DNA the genetic blueprint in the early 1950s, steady and unrelenting progress has been made in the biotechnology field. With the announcement of the birth of Dolly the transgenic sheep, and the announcement by Richard Seed that he plans to start a human cloning business, the world's attention has focused on the biotechnology of cloning. This article will review some of the history and patent aspects of cloning technology as the debate on human cloning continues.

What is Cloning?

Cloning generally means the isolation and duplication of genes or cells. Researchers have been cloning animal, plant and other organism cells and genes for over twenty years. Cells can be cloned by isolating them from the body through a biopsy and culturing them. The cells will grow and divide, producing new cells identical to the original cells. The resulting cells, called a 'cell line', have an identical genetic makeup.

In the normal development of a mammal, a sperm and an egg containing DNA fuse to form a new cell, or zygote, with a complete genetic complement. The zygote divides into multiple identical cells that grow and differentiate into various types of cells, such as those which build the nervous system, etc. The zygote develops into an embryo and eventually into a mammal.

On July 5, 1996 Dolly was cloned using a technique known as 'somatic cell nuclear transfer technology'. A somatic cell is any cell of the embryo, foetus, child or adult which contains a full complement of two sets of chromosomes. Germ cells, i.e. an egg or a sperm, contain only one set of chromosomes. In this technology, a cell nucleus containing complete DNA from any somatic cell is transferred into an egg from which the nucleus has been removed and grown into an embryo. In Dolly's case the nucleus from an udder cell of one lamb was introduced into an egg from another lamb.

Major Benefits From Cloning

Cloning techniques are invaluable in the development of biotechnology. They have led to the identification of proteins and the development of breakthrough medicines, diagnostics and vaccines to treat heart attacks, haemophilia, anaemia, various cancers, hepatitis, and other diseases.

Cloning technology is important in many areas of research, including nerve, muscle and skin cell repair. The understanding of early cell growth and specialisation will continue to contribute to the diagnosis, treatment and care of many diseases. Researchers are increasingly interested in undifferentiated cells and the potential for genetic engineering, including entire gene transformation. Cloning technology is also making important contributions in the plant and animal fields where enhanced traits and improved properties are often accomplished through cloning.

Issues

For the scientific community and intellectual property counsel the everpresent question is whether and to what extent they may obtain patents on cloning particularly human cloning. An understanding of the public debate, particularly the legislative initiatives is important to understand this issue.

The Response

When the press announced the birth of Dolly on February 24, 1997 President Clinton turned to the National Bioethics Advisory Committee (NBAC) for a thorough review of the technology. The NBAC considered the question of human somatic cell transfer cloning and issued its report in June. The Commission concluded that 'at this time it is morally unacceptable for anyone in the public or private sector, whether in a research or clinical setting, to attempt to create a child using somatic cell nuclear transfer cloning[1].

The NBAC also recommended federal legislation to prohibit such cloning for three to five years[2].

There is essentially uniform opposition to the creation of a human clone within the scientific community at least among those capable of cloning a human being. The American Society of Reproductive Medicine, The Biotechnology Industry Organisation and The Federation of American Societies of Experimental Biology have all stated that their members will not seek to clone a human being.

Additionally, on February 9, 1998 twentyseven Nobel prize winners sent a letter to President Clinton and all members of Congress supporting the voluntary ban on human cloning by the American Society of Cell Biology. Thus, for the time being it appears that no reputable scientist will clone a human being.

Jurisdiction Over Cloning

The Federal Government has already asserted jurisdiction over human cloning. The Food and Drug Administration (FDA) has publicly stated that it has authority over any proposal to clone human beings. This authority over somatic cell and gene therapy products arises from the Public Health Service Act (PHS) and the Federal Food, Drug and Cosmetic Act (FD&C)[3]. Under this authority the FDA will require any doctor or scientist desiring to clone a human to meet its licensing requirements. Richard Seed, who recently announced that he was establishing a human cloning service must therefore satisfy FDA requirements.

Federal Cloning Legislation

The response from Congress has been swift. Congress cut off all funding of cloning research by the Federal Government. The House and Senate Appropriations Bills for Fiscal Year 1998, H.R. 2264, both include a ban on federally funded embryo research. Both provisions amend the ban on embryo research in the Fiscal Years 1996 and 1997 bills by adding a prohibition on funding of embryo research involving 'human diploid cells', a reference to human cloning.

The Clinton Adinirtistration has made a proposal that would ban the cloning of a human being by anyone, regardless of the source of funding. The legislation would impose severe penalties taken from the racketeering statutes for violations, including fines of at least $250,000 and complete confiscation of 'any property, real or personal, derived from or used to commit a violation or attempted violation ... or any property traceable to such property.

Congressman Vemon Effiers has introduced two bills, H.R. 922 and R.R. 923. The first bans the use of any Federal funds to clone a human being and the second bans any human cloning irrespective of whether the research is funded by the Federal government.

Senator Kit Bond has introduced S.368, a bill that provides that 'No Federal funds may be used for research with respect to the cloning of a human individual'. The Bill defines the term 'cloning' to mean 'the replication of a human individual by the taking of a cell with genetic material and the cultivation of the cell through the egg, embryo, foetal, and newbom stages into a new human individual'.

More recentIy, Senators Bond, Feist and Gregg introduced S.1599, reintroduced as S.1601, 'Human Cloning Prohibition Act of 1998'. This Bill would amend Title 18 by banning the'use'of human somatic cell nuclear transfer technology and the importation of an embryo produced with the technology. Violation would result in both civil and criminal penalties.

S.1602, 'Prohibition of Cloning of Human Beings Act of 1998' which was introduced by Senators Feinstein and Kennedy adopted the NBAC recommendations and sought to prohibit 'any attempt' to clone a human being using somatic cell nuclear transfer and to prohibit funding for such attempts. The Bill would amend the Public Health Services Act. Civil fines of at least $1,000,000 are provided for. The Bill provides for federal preemption of state or Gcal laws prohibiting the proscribed activities. Other cloning bills include: H.3133 (Stearns) and S.1574 (Campbell).

The major debate on all of the Bills is fine tuning them to prohibit the creation of a human clone while allowing medical scientists to conduct needed medical research.

State Cloning Legislation

The federal government is not the only governmental branch taking steps to regulate cloning. As this article is written, sixteen states[4] have proposed or enacted legislation to prohibit human cloning, criminalise cloning, prevent trafficking in ova, zygotes, embryo or foetal material for human cloning, prohibit research funding for human cloning, create property rights in genetic information or moratoriums on human cloning, and to prohibit conspiracies to clone a human.

The Development of Biotechnology Patents

Article 1, Section 8, clause 8 of the Constitution grants Congress authority to 'promote the Progress of Science and the Useful Arts' by securing to inventors the rights to their works for a limited time. This grant has been implemented by the Patent Act, Title 35 U.S.C. Patentable subject matter must be new, useful and nonobvious. Patentable inventions are 'useful processes, machines, manufacturers, or compositions of matter'. Unlike many foreign statutes, such as Article 53 of the European Patent Act which prohibits patents that offend morality or public order, there is no express statutory prohibition in the US Patent Act that would block a patent for transgenic humans.

Congress and the courts on occasion have created 'public policy' exemptions from patents. Laws and products of nature are not patentable[5]. Purely mathematical equations or naturally occurring chemicals do not fall with the statutory subject matter of 35 U.S.C. §101.

Certain legislative attempts to curtail patent rights also exist. For example, the Atomic Energy Act excludes patents for military uses of fissile materials[6]. More recently, the American Medical Association and the Pharmaceutical Research and Manufacturers of America successfully lobbied Congress to pass an exemption from patent infringement liability for physicians carrying out medical procedure[7].

The modem law of biotechnology traces its beginning to the Chakrabarty case in which the inventor claimed genetically engineered microorganisms designed to 'eat' oil spills. The examiner rejected the claims because they were 'products of nature'. The United States Supreme Court rejected this position and ruled that claims to recombinant living organisms were not products of nature. Further, the Court ruled that such organisms were within the 'manufacture' and composition of matter' categories of patentable subject matter.

'Manufacture' and 'composition of matter', the Court said, cover 'anything under the sun made by man' and left to Congress the task of circumscribing statutory subject matter[8]. Shortly after the Chakrabarty decision applications for patents on multicellular organisms were filed[9].

In 1987 the United States Patent and Trademark Office (USPTO) issued a Policy on the Patenting of Animals. The USPTO'considers nonnaturally occurring nonhuman multicellular living organisms, including animals, to be patentable subject matter within the scope of 35 U.S.C. §101.'

On April 12,1988 the USPTO issued the first transgenic animal patent for the Harvard Mouse. Claim 1 of US Patent No. 4,736,866 is: 'A transgenic nonhuman mammal all of whose germ cells and somatic cells contain a recombinant activated oncogene sequence introduced into said mammal or an ancestor mammal at an embryonic stage'. Since then, some eightyfive transgenic animal patents have been issued and, according to the USPTO about ninety more transgenic animal patents have been allowed and will issue soon.

Transgenic animals have been invaluable as testing models for a variety of diseases, treatments, and therapies and can be used for the production of pharmaceuticals and organ transplants. Examples include the production of human proteins in cow's milk and human haemoglobin in pigs. Livestock improvements have taken the form of transgenic animals that have improved traits, e.g. larger leaner animals and animals resistant to disease,

On March 21,1995 the USPTO issued the first patent for human gene therapy to NIH researchers French Anderson, Michael Blaese and Steven Rosenberg, US Patent No. 5,399,346. This patent claims the method of perfomming gene therapy in humans. The technology involves the insertion of new DNA into the cells of a human.

Patenting of Cloned Humans not Likely

With the patenting of gene therapy the question naturally arises can one obtain a patent on the cloning of a human being? The USPTO believes that transgenic humans are excluded from patentability by the Thirteenth Amendment of the Constitution which prohibits slavery and involuntary servitude of another human being. Some commentators have questioned the USPTO's claim to the XIII Amendment exclusion. It has also been suggested that a right of reproductive freedom under the Fourteenth Amendment might bar the patenting of human clones.

A more fundamental statutory issue is whether a claim to a transgenic human would satisfy the statutory requirement of the Patent Act. There may be a distinction between a 'normal' clone in which an entire somatic cell nucleus is transferred and an 'engineered' clone where the donor DNA is modified prior to transfer. The 'normal' transgenic humans would be essentially identical human beings (ignoring their memory /character). A claim to such a 'normal' transgenic human would face some difficulty in overcoming the novelty requirement of the Patent Act[10]. The belief that truly identical but 'delayed' twins would result from human somatic nuclear cell transfer cloning is not accurate. While the nuclear genetics would be identical the interaction among the individual's genetic, physical, cultural and environmental factors and the process of learning results in a unique individual. However, at birth and for a period of time thereafter, these factors would not have had any effect and the 'delayed' twin may lack novelty within the meaning of 35 U.S.C. §102. The 'engineered' transgenic however, would be different from birth and thus could satisfy the novelty requirement.

Some Claims to Human Cloning can be Expected

Patents on human clones are not likely to be issued in the US for the foreseeable future. The current stance of the USPTO that such patents violate the Thirteenth Amendment coupled with voluntary moratorium and the forthcoming legal bar to human cloning appear to end the patent debate on specific patents to cloned humans. However, technology leading up to a human clone may likely be subject to patent protection. Creative patent draftmanship may yield patent claims that would cover aspects of human cloning. For example, a method of making a human clone rather than the clone itself may well be patentable and has been the subject of debate at Patent Office.

Roundtable discussions.

What result would follow if these types of claims were sought, rejected by the USPTO and taken on appeal? Would a court follow the USPTO's position that such claims are barred by the US Constitution? Will the Supreme Court hold them patentable because they are 'anything under the sun made by man?' An amendment to the Patent Act may be required to circumscribe this issue[11].

Conclusion

For the foreseeable future, specific patents for human clones are unlikely. However, claims to methods and components for use in human cloning can be expected. It should also be anticipated that currently pending legislation and voluntary moratoriums on human cloning will prevent the actual cloning of humans in the United States for some time.

1998 William S Feiler, BE, JD, LLM (in Trade Regulation) is a partner at Morgan & Finnegan, LLP, New York, NY, where he specialises in biotechnology litigation. Mr. Feiler is counsel to the National Institute of Health. Website:
http://www.morganfinnegan.com

Notes [1]NBAC, Cloning Human Beings (1997).

[2]Id. [3]42 U.S.C. §201 et seq; 21 U.S.C. §201 et seq. [4]The states include Alabama, California, Florida, Illinois, Indiana, Michigan, Mississippi, New Hampshire, New Jersey, New York, North Carolina, South Carolina, Ohio, Pennsylvania, Rhode Island, Tennessee. [5]See Funk Bros Co v Kalo Inoculant Co, 333 US 127 (1948); Diamond v Dieker, 450 US 175 (1981). [6]42 U.S.C. §2181(a) (1988). [7]35 U.S.C. § 287(c). [8]Diamond v Chakrabarty, 447 US. 303 (1980). [9]Ex Parte Allen, 2 U.S.P.Q.2d 1425 (PTO Bd. App. & Int. 1987); Ex Parte Hibberd, 227 U.S.P.Q. 443 (PTO Bd. App. & Int. 1985). [10]35 U.S.C. §102. [11]Cf. Chakrabarty, 447 US. at 317-318.

Patent World - May/June 1998 - pp. 20-23