Professor Merges

Patent Law

Professor Merges

Spring 2005

Take-Home Exam

This exam has fivepages. Please use only your casebook, notes, and statutory supplement. You have 24 hours from exam pick-up to drop off. Good luck, and have a great summer!

Question

Federal Pharmaceuticals (FP) is a large pharmaceutical company engaged in a wide variety of pharmaceutical research. In June of 1982, researchers Alexa Hamilton and Jamie Madison were working on a project to identify compounds useful in treating depression, eating disorders, and other psycho-physiological problems. They had honed in on a family of molecules known as “Tertiary 2-phenoxy-2-phenylethylamines,” or “T22’s” for short. T22’s were first identified and described in a 1973 publication by several Japanese researchers in the Journal of the Pharmaceutical Society, Japan, vol. 53, pp. 508-519 (1973). This publication described the structure of T22’s and also noted that, in preliminary lab tests with mice subjects, they “appeared to have good mydriatic action,” that is, they tended to dilate the pupils of the mice’s eyes. They were therefore thought to be promising as possible molecules to form the basis of eyedrops to study eye dilation.

In 1983, researchers at the University of Toronto published an article in the British Royal Pharmaceutical Society’s “Proceedings” describing their research into various “mydriatic” agents. They found that many of the molecules studied had much more far-reaching effects on mice (and, presumably, other animals – including humans). In particular, they appeared to have a significant effect on the eating habits of mice that had been bred to show obesity. This in turn, according to the Toronto researchers, suggested that many of these mydriatic molecules might be affecting the basic brain chemistry of the mice, which meant that they could have broader psycho-physiological effects than was previously thought.

The FP researchers, Alexa and Jamie, concentrated on making variations in T22 molecules. They were particularly interested in exploring molecules that tended to increase the available amount of a key brain chemical, called serotonin, which helps to transport signals across brain cells (neurons). Lower than normal levels of free or available serotonin are associated with eating disorders, depression, and many other psychophysiological problems. Alexa and Jamie were trying to synthesize a variant on the T22 structure that could prevent serotonin that had been produced in the brain from being reabsorbed by brain cells. But they were also trying to avoid problems that related molecules had shown, in particular that certain T22-related molecules can bind to brain cells in a way that causes bad side effects, such as terrible headaches. Thus Alexa and Jamie were looking for what they described as a “selective serotonin reuptake inhibitor,” or SSRI.

On June 19, 1982, Alexa and Jamie isolated a molecule they dubbed “T22-M.” They called it this because to make it, they substituted “methyl” side groups for a number of Hydrogen atoms in one well-known T22molecule. (A methyl group is made up of one carbon and three hydrogen atoms, and is abbreviated CH3.) While it is very well known in the chemistry field that a methyl group can be substituted for a hydrogen atom in many chemical compounds, Alexa and Jamie could not find any other scientific publication or patent that disclosed this molecule. Given that it was a new molecule, and that they thought it might hold great promise, they helped draft a patent application describing it and related molecules. They used the following chemical structure diagram in their draft patent application:

And they disclosed that the R’ groups in the diagram could all be either methyl or propynl groups (C3H5). (Propynl is very well known as a side group that often functions similarly to a methyl group, so it was a logical choice as an alternative to methyl.)

One embodiment of this basic structure is the molecule fluoxetine hydrochloride (“Molecule FH”). This was the molecule that FP researchers chose to test first after Alexa and Jamie described their research results, because it was easy to make and was very stable (i.e., did not break down over time). This testing had just begun when FP filed a patent application on the “T22-M” family of molecules on June 26, 1982. This initial patent application disclosed the T22-M chemical structure, and stated that the claimed molecules “are structurally closely related to other molecules that have shown great promise against eating disorders and other psych-physiological diseases.” After six months of initial tests in mice showed great promise for Molecule FH, the patent application was updated (on January 7, 1983) to include mouse testing data.

In March, 1984, the T22-M patent issued. (Just prior to issuance, FP filed a “continuation” patent application that carried forward the original disclosure of the T22-M patent application. This is common practice, done to enable improvement or variation inventions to be claimed based on the original filing of a patent application.) That same month, the Food and Drug Administration (FDA) approved Molecule FH for use as an anti-overeating and anti-depressant drug. Almost instantly, stories began to appear in newspapers and on TV about the revolutionary effects of the drug, which was sold under the trade name “Praxil.” People who had suffered severe depression for many years reported amazing stories of reclaimed vigor and happiness. Sales climbed to over $3 billion annually. Molecule FH was a big hit!

In 1995, FP began planning for the expiration of the Praxil patent, which would take place in March, 2004. FP scientists went to work examining the detailed mechanism by which Molecule FH operates. In January of 1996, they discovered through lab tests that serotonin uptake is achieved in the brain when serotonin binds with a specific protein on the surface of neurons. The FP researchers dubbed this protein the “serotonin transport receptor,” or “SERT” for short. The researchers then assisted in the drafting of a patent application, filed as a continuation of the original T22-M application, disclosing and claiming this mechanism. Claim 1 from this continuation application reads as follows:

1.A method of treating depressive mood disorders in a human by blocking the uptake of serotonin by brain neurons comprising administering to said human a chemical entity capable of binding with the SERT receptor present on brain neurons, in sufficient amount to effectively block serotonin uptake.

This continuation was filed in February, 1996. In May, 1996, the patent examiner assigned to the case issued a rejection of claim 1, arguing that it was indefinite, based on the fact that she could not find the term “depressive mood disorders” in a standard psychological disorders handbook available in the Patent Office library. The FP patent lawyer assigned to the case called Alexa and asked if researchers in her field made any distinction between “depression” and “depressive mood disorders.” Alexa said “No, they are basically synonyms in my field.” (In fact, there is a disagreement over this issue; the official Psychiatrist’s Desk Reference Book, issued by the American Psychiatric Association, makes no distinction between them, but the Clinical Psychology Diagnosis Guide defines “depressive mood disorders” more broadly than depression, saying that it includes “disorders such as high-depression manifesting versions of Obsessive-Compulsive Disorder.”) But, relying on Alexa’s information, the FP patent lawyer submitted the following amendment to claim 1:

1.A method of treating depression in a human by blocking the uptake of serotonin by brain neurons comprising administering to said human a chemical entity capable of binding with the SERT receptor present on brain neurons, in sufficient amount to effectively block serotonin uptake.

This satisfied the examiner, who authorized the patent to be issued, which occurred in December of 1996. It is known as the “SERT” patent.

Meanwhile, several researchers at Aaron Burr Laboratories (AB) were working on similar approaches to depression and related disorders, including specifically synthesis and lab testing of various molecules in the T22 family.

In late 1981, AB had received a “request for proposals” from the US Army requesting “pioneering pharmaceutical approaches to depression.” This request was made under a recently-passed statute authorizing the armed services to “attack depression-related disorders as aggressively as possible”; the statute had been passed at the urging of a prominent Senator whose daughter, a military veteran, had committed suicide in early 1981. The statute provided extraordinary incentives to encourage pharmaceutical researchers and drug companies to take “the boldest possible action.” One provision, for example, prohibited legal liability for late or incomplete performance of contractual obligations pertaining to experimental drugs, on the theory that this would encourage drug companies to make far-reaching commitments. In response, AB had prepared a document entitled “Offer of Commercial Quantities of Experimental Depression Treatment Drugs” (AB Offer). The AB Offer recited that AB was actively engaged in numerous depression-related research projects. It promised that AB would deliver “at least 250 doses” of an experimental depression-treatment drug “that is markedly more effective than existing therapies,” by September, 1985; and that the drug would be “based on the well-known T22 molecules currently under study at [AB].” The AB Offer was transmitted to the Army on January 5, 1982.

In November, 1983, several AB researchers were attending a scientific conference on new approaches to depression treatment, when they attended a presentation by Alexa and Jamie of FP. During a hallway conversation, Alexa and Jamie mentioned their work with T22-related molecules, and specifically mentioned their good progress with fluoxetine hydrochloride (“Molecule FH”), whose structure they described briefly. As soon as they returned to their lab at AB, the researchers quickly synthesized Molecule FH. Then, because they assumed that FP was seeking a patent on this molecule, they made some structural variations. One of these, which they deemed T22-MH, was identical to Molecule FH, except that in place of one methyl group they substituted a hydrogen atom (H). (Remember, methyl groups and hydrogen are often interchangeable.) They then proceeded to file a patent application covering T22-MH on January 7, 1984; after extensive prosecution, the patent finally issued in 1990. Claim 1 of AB’s T22-MH patent recites the chemical structure of the T22-MH molecule, which again is very similar to the structure of FP’s T22-M molecule. Claim 2 was based on research published in December, 1983, describing the formal recognition of a new mood-related condition: “Bipolar Disorder.” The research described how in the past, psychiatrists had identified certain depressed patients who periodically passed through highly energetic periods. They were sometimes called “cyclic depressives.” But the new research in 1983 showed convincing evidence that patients who undergo this cyclic type of behavior have slightly different brain chemistry than other patients with depression. The research publication did state, however, that “the brain chemistry is probably not so different that conventional depression medications will not have at least some effect with patients suffering from bipolar disorder.” It was in response to this information that the AB researchers added a hastily-written paragraph on bipolar disorder to the specification of the T22-MH application, as well as a new Claim 2, which reads:

2.A method of treating bipolar disorder in a human by administering to said human a chemical entity capable of binding to brain neurons, said chemical entity drawn from the group of [T22-M and T22-MH].

This patent application issued in 1986. Just as FP had, AB filed a continuation of this application before it was issued. After FP’s SERT patent issued in December of 1996, AB amended the still-pending continuation application by adding the following claim:

12.A method of treating bipolar disorder in a human by blocking the uptake of serotonin by brain neurons comprising administering to said human a chemical entity capable of binding with the SERT receptor present on brain neurons, in sufficient amount to effectively block serotonin uptake.