“(2) An invention of a method of treatment of the human or animal body by surgery or therapy or of diagnosis practised on the human or animal body shall not be taken to be capable of industrial application. (3) Subsection 2 above shall not prevent a product consisting of a substance or composition being treated as capable of industrial application merely because it is invented for use in any such method.”
“(6) In the case of an invention consisting of a substance or composition for use in a method of treatment of the human or animal body by surgery or therapy or of diagnosis practised on the human or animal body, the fact that the substance or composition forms part of the state of the art shall not prevent the invention from being taken to be new if the use of the substance or composition in any such method does not form part of the state of the art.”
“The novelty of the second medical use, on which its patentability rests, must therefore be found in applications that are new in the terms used in Wyeth and Yew-tree. The novelty cannot lie in the method of use, but in the new therapeutic purpose for which the substance is used.” c. [Holman J]: “108. I respectfully agree with the analysis by my Lord, Buxton LJ as to the limits of second medical use claims, the validity of which was recognised by the Enlarged Board in Eisai. The conclusion of the Enlarged Board, as expressed in the last paragraph (23) of their decision, clearly refers to “a specified new and inventive therapeutic application”
“Accordingly, the present invention is particularly concerned with providing a method of treating the hyperandrogenic conditions of androgenic alopecia, including male pattern alopecia, acne vulgaris, seborrhea, and female hirsutism by topical administration, and a method of treating all of the above conditions as well as benign hypertrophy, by systemic administration, of the novel compounds of the present invention. The compositions containing the compounds of the present invention is [query should be “which are”] the active ingredient for use in the treatment of benign prostatic hypertrophy can be administered in a wide variety of therapeutic dosage forms in conventional vehicles for systemic administration, as for example, by oral administration in the form of tablets, capsules, solutions, or suspensions, o[r] by intravenous injection. The daily dosage of the products may be varied over a wide range varying from 5 to 2,000 mg, preferably from 5 to 200 mg.”
“In the end the question is simply "was the invention obvious?" This involves taking into account a number of factors, for instance the attributes and cgk of the skilled man, the difference between what is claimed and the prior art, whether there is a motive provided or hinted by the prior art and so on. Some factors are more important than others. Sometimes commercial success can demonstrate that an idea was a good one. In others "obvious to try" may come into the assessment. But such a formula cannot itself necessarily provide the answer. Of particular importance is of course the nature of the invention itself.”
“The facts were simple: there was a known process. The patent was for the old process using the new agent. It was held obvious as being “well worth trying out”
‘It is enough that the person versed in the art would assess the likelihood of success as sufficient to warrant actual trial.’
“There is no basis in law or in logic for including within the concept of “a person skilled in the art” a person who is not directly involved in producing the product in question in the patent or in carrying out the process of production”
“The Court is trying to determine in a common sense way how the average skilled but non-inventive technician would have reacted to the pleaded prior art if it had been put before him in his work place or laboratory. The common general knowledge is the technical background of the notional man in the art against which the prior art must be considered. This is not limited to material he has memorised and has at the front of his mind. It includes all that material in the field he is working in which he knows exists, which he would refer to as a matter of course if he cannot remember it and which he understands is generally regarded as sufficiently reliable to use as a foundation for further work or to help understand the prior art.”
“In my judgment it is not sufficient to prove common general knowledge that a particular disclosure is made in an article, or series of articles, in a scientific journal, no matter how wide the circulation of that journal may be, in the absence of any evidence that the disclosure is accepted generally by those who are engaged in the art to which the disclosure relates. A piece of particular knowledge as disclosed in a scientific paper does not become common general knowledge merely because it is widely read, and still less because it is widely circulated. Such a piece of knowledge only becomes general knowledge when it is generally known and accepted without question by the bulk of those who are engaged in the particular art; in other words, when it becomes part of their common stock of knowledge relating to the art. Whatever else common general knowledge may be, it has never in my judgment included public knowledge of particular documents, reports or scientific papers and the like…..It is certainly difficult to appreciate how the use of something which has in fact never been used in a particular art can ever be held to be common general knowledge in the art". That passage was accepted by the Court of Appeal in Beloit Technologies (see next paragraph) with the reservation for further consideration: “whether the words “accepted without question” may not be putting the position rather high: for the purposes of this case we are disposed, without wishing to put forward any full definition, to substitute the words “generally regarded as a good basis for further action”. b. Aldous LJ in Beloit Technologies Inc v Valmet Paper Machinery Inc[1997] RPC 489 at 494: “It has never been easy to differentiate between common general knowledge and that which is known by some. It has become particularly difficult with the modern ability to circulate and retrieve information. Employees of some companies, with the use of libraries and patent departments, will become aware of information soon after it is published in a whole variety of documents; whereas others, without such advantages, may never do so until that information is accepted generally and put into practice. The notional skilled addressee is the ordinary man who may not have the advantages that some employees of large companies may have. The information in a patent specification is addressed to such a man and must contain sufficient details for him to understand and apply the invention. It will only lack an inventive step if it is obvious to such a man.” c. Laddie J in Pfizer at paragraph 66 where he drew attention to the circumstances in which the common general knowledge of the skilled man would cause him to indulge in some form of literature search as a result of reading the prior art document in question: “When any piece of prior art is considered for the purpose of an obviousness attack, the question asked is “what would the skilled addressee think and do on the basis of this disclosure?”
“The skilled man has his common general knowledge – the mental tools of his trade – but no more. The law of obviousness supposes that he can be given any individual piece of prior art and read it with that knowledge. The piece of prior art forms part of the “state of the art”
“…….In summary, they reported the biochemical basis of a rare human genetic disease in which affected males were born without prostates and with female external genitalia. As adults, these subjects were said to have normal male libido, deep voices and male musculature but not to develop acne or exhibit male pattern baldness. The two teams of investigators used different experimental methods to show that these patients failed to synthesise DHT in certain tissues because they had inherited defects in the gene that specified 5α-reductase. The striking presentation of these individuals suggested that testosterone and DHT had different physiological effects. Testosterone was required for some aspects of the male phenotype, including libido, vocal cord maturation and muscle development at puberty, whereas DHT was required for the development and growth of the external genitalia and the prostate. Furthermore, the failure to develop acne suggested that DHT controlled the activity of sebaceous glands, which are responsible for secreting skin oil. The fact that affected males had a full head of hair as adults appeared to indicate that DHT contributed to the development of male pattern baldness. The latter activity deserves further consideration given the present case. A role for androgens in hair growth was recorded by Aristotle who wrote in describing men castrated as youths “The congenital growth of hair never falls out, for a eunuch never goes bald”……. More recent studies done by Hamilton on mentally defective men in the 1940s who were castrated based on eugenics principles, confirmed and extended Aristotle’s conclusions. Hamilton had access to purified testosterone and showed that administration of this androgen to eunuchs sterilised as boys caused them to develop male pattern balding ……. Although the anatomy of the hair follicle was well-established by Hamilton’s time (see Figure 1), experiments to determine which cells in the structure responded to androgen and whether testosterone or DHT was the active hormone were not forthcoming until the papers of Walsh and Imperato-McGinley in the 1970s. The findings presented in the Walsh and Imperato-McGinley papers caught the attention of pharmacologists at several universities and large pharmaceutical companies who reasoned that if inhibitors of 5α-reductase could be identified, then these might be useful as drugs for the treatment of benign growth of the prostate, acne and baldness. When an enzyme catalyses a reaction, it binds the starting compound, referred to as the substrate, and then transforms the substrate into a product. In the case of 5α-reductase, the enzyme binds testosterone and then converts this substrate into the product DHT. To stop or block this enzyme, a pharmacologist attempts to identify molecules, typically small molecules, which bind to the enzyme and prevent it from transforming the substrate into product. Such inhibitors are known to act in different ways. Sometimes, an inhibitor will compete with the substrate for binding to the enzyme. In other cases, such as with finasteride, the small molecule inhibitor developed by Merck to block 5α-reductase, more complicated mechanisms of inhibition take place. During the late 1970s and 1980s, many different inhibitors of 5α-reductase were identified in academia and industry, and their use in the treatment of human disease began to be established in clinical trials.”
"Therefore, retardation of the conversion of testosterone to DHT by 5 alpha-reductase inhibition seems to be not only an additional mechanism to stimulate hair regrowth, but also a potential conjunctive therapy to minoxidil as a remedy for male-pattern baldness."
“The data in this paper are more rigorous than those of the slightly earlier Harris paper (which Thigpen cites at reference 32) in that they are derived not only from the pharmacological method used in Harris, ie. pH dependence, but also from an immunological method and a molecular biological method. Thigpen shows developmental expression patterns of the two 5α-reductase isozymes in the liver, skin and scalp. In the liver, the two isozymes had an identical temporal pattern of expression. However, in the skin, the two isozymes differed in their expression patterns. Both were detected in the dermis of neonates through age 3 years; thereafter, expression of both isozymes is extinguished until puberty (around age 15) at which time expression of the type 1 isozyme is induced to high levels (no type 2 isozyme was detected). The finding of the type 1 isozyme in the scalp is surprising given the reported absence of hair loss in type 2 deficient subjects. Thigpen speculates that the pulse of type 2 expression near birth may influence the development of baldness in later life. Thigpen found no qualitative differences in the steady state levels of type 1 reductase in the scalps of balding and non-balding men, nor were there any regional expressional differences detected across the balding scalp. Thus, at the level of resolution afforded by this study, no evidence for abnormal expression of type 1 isozyme as a feature of male pattern balding was found. Thigpen thus suggests that balding might be treated by a type 1 inhibitor while a type 2 inhibitor is unlikely to be effective in scalp skin (since the data suggested the type 2 isozyme is absent in the adult scalp). In my discussions as a consultant to Merck, I therefore suggested to Dr Ed Scolnick around the time of publication of Thigpen that Merck should concentrate on developing a type 1 inhibitor for male pattern baldness.”
“In humans, two 5α-reductase isoenzymes have been identified, numbered 1 and 2. Their tissue distribution in humans has not been determined. In the rat model 5α-reductase-1 is in all tissues at very low concentrations, and 5α-reductase-2 is limited largely to the urogenital tract. Finasteride is much more specific to inhibition of 5α-reductase-2 than 5α-reductase-1, although it works with both.”
“The role of 5α-reductase inhibitors may not be limited to treatment of BPH. [DHT receptors] and 5α-reductase enzyme systems are located in the prostate, as well as in the skin and sebaceous glands. The former may play a major role in prostate cancer, male-pattern baldness, female hirsuitism, and acne. Recent research has focused on finasteride’s potential use in several of these conditions, including prostate cancer and male-pattern baldness; Merck presently has no plans for clinical trials in female hirsuitism or acne”
“Results from this study suggest a role for finasteride in reversing established baldness. It also appears that the combination of finasteride and minoxidil may be more effective than either agent alone. Development of a topical finasteride product would allow local treatment of baldness without significant systemic alteration of androgens. Clinical trials in humans are planned to establish the drug’s role as either single-agent therapy or in combination with minoxidil in the treatment of male-pattern baldness.”
“The adverse events associated with finasteride are limited and predictable due to its specificity as an inhibitor of 5α-reductase. Unpublished manufacturer reports summarising adverse events in approximately 2500 patients demonstrate the drug’s excellent clinical tolerance and safety profile. Safety experience to date includes single-dose therapy (up to 400 mg), dose-ranging therapy (0.2-80 mg) for 3 months, and 3 years’ experience with the currently approved dosage of 5 mg once/day. No reports exist in the published literature of finasteride overdose, although in clinical trials patients received single doses as high as 400 mg and multiple doses of up to 80 mg/day for 3 months continuously without any drug-related adverse event. … In summary the drug has an excellent safety and tolerability profile. The overall frequency of adverse events is low. Most are sex related and may require discontinuation of therapy in a small number of patients; however these symptoms may be transient, as demonstrated in clinical trials”
“I can recall having such concerns [ie the usefulness of the scalp samples actually used in the studies] at the time and did not believe it was possible to draw any firm conclusions from them about the isozyme type expressed in the hair follicle and specifically the dermal papilla.”
“Additional studies are required to fully characterise the skin reductase(s)”
“Oral administration of finasteride at around 0.5 mg/day in an estimated 10 kg macaque, a balding animal model, in combination with topical minoxidil had been shown by Diani in a single experiment to increase hair weight more significantly than minoxidil alone. The data for administration of finasteride alone were not conclusive. The combination of topical minoxidil and oral finasteride was thus more promising.” i. Rather, according to Mr Thorley, the take home message included, as indicated in the abstract, that: “finasteride increased hair weight in 4 out of 5 monkeys” j. Indeed Professor Russell himself accepted in cross-examination that Diani provided grounds for further investigation of finasteride alone. k. It is worth remembering, I would add, that all these issues arise in the context of what was recognised as something of a puzzle. In addressing Thigpen in cross-examination, Professor Russell was asked whether he was surprised to find type 1 present in the heads of potentially balding and potentially non-balding men and answered that he was surprised. When asked whether this did not indicate that type 1 was not playing a part in MPB he replied in this way: “No. It illustrated the conundrum that you referred to earlier, and that was on the one hand you had the genetic results arguing that it should be type 2, and on the other hand we had strong biochemical and immunochemical data saying that type 1 was the major enzyme in the skin. That to us was hard to explain.”
“Sudduth teaches that finasteride is a promising treatment for androgenic alopecia. The difference between this and the inventive concept of claim 1 of the Patent is the discovery that oral finasteride is an effective treatment for androgenic alopecia at doses of between 0.05 – 1.0 mg per day.”
“As at 1993, whilst one could not rule out the possibility that a type 1 inhibitor would make a possible drug target for the treatment of MPB, there was no clear evidence that type 1 was expressed in the hair follicle. My own thinking at the time was that there were some parallels to be drawn between the prostate and androgen dependent hair follicles in terms of androgen action. This was based partly on the observations of prostate development and male hair distribution in 5α-reductase type 2 deficient men (Imperato-McGinley (1974)). In addition, a study by Itami et al, had demonstrated that the 5α-reductase present in dermal papilla cells from androgen dependent beard follicles was similar to that found in the prostate but dissimilar to that present in dermal papilla cells from non-androgen dependent occipital scalp follicles. Taken together these observations provided evidence that the 5α-reductase in the dermal papilla of the balding scalp follicles could also be the same as that present in the dermal papilla of the beard follicles and in the prostate, since all of them are androgen dependent tissues. Accordingly, in 1993 there were good grounds for believing that male androgen dependent hair follicles might well be mediated by the type 2 5α-reductase isozyme.”