No financial details were available on the agreement, under which Pharming will pay ACT a one-time licence fee for exclusive global rights to patents in the field of transgenic technology.
Pharming already had non-exclusive rights to these patents through prior agreements with Infigen, a former competitor to Advanced Cell Technology whose intellectual property (IP) assets relating to somatic cell nuclear transfer, parthenogenesis and other associated technologies were acquired by ATC in February 2007.
The Dutch company said the patents previously owned by Infigen cover " a wide range of technologies, including for Pharming relevant elements of nuclear transfer, which is an essential step in generating transgenic cattle ".
The agreement with ATC gives Pharming " strict control over the generation of its transgenic cattle while, at the same time, increasing the barriers of entry for others ", it added.
According to ATC, the licence relates to " non-human use of certain patents associated with, but not limited to, oocyte activation patents held by Advanced Cell Technology ".
As the company noted when it acquired the Infigen IP portfolio, 'parthenogenetic activation' or the activation of oocytes ('egg cells') - female gametocyte s or germ cell s involved in reproduction - is a critical step in somatic cell nuclear transfer (SCNT).
Infigen had invested heavily in IP for animal cloning and had filed " some of the earliest and most strategic patents in fundamental steps related to SCNT ".
Under a previous royalty-bearing cross licence, ATC had secured the freedom to operate under the Infigen patents in the field of human cell therapy.
The acquisition of 26 issued patents and " numerou s" pending applications from Infigen removed any royalty obligations and gave ATC exclusive ownership of the relevant patents for use in regenerative medicine programmes and licensing animal applications.
For its part, Pharming announced in July 2004 that it had renegotiated the terms of previous licensing agreements with Infigen to obtain worldwide, non-exclusive, royalty-free and non-terminable licences to patents on nuclear transfer and associated technologies.
This would enable Pharming to advance commercialisation of its product pipeline and protein production technology, the Dutch company said.
The listed IP portfolio acquired by ATC from Infigen includes US patents for the in vitro activation of mammalian ooocytes and their use in cloning procedures; for ungulates (hoofed animals) produced by sequential nuclear transfer; for methods of producing a polypeptide in an ungulate, cloning bovine embryos and cloning bovines using reprogrammed non-embryonic bovine cells; for parthenogenic oocyte activation and parthenogenic bovine oocyte activation; and for multiplying bovine embryos.
Pharming owns or licenses some 36 patents on various aspects of transgenic technology and products derived from the milk of transgenic animals.
The company produces therapeutic proteins such as Rhucin (recombinant human C1 esterase inhibitor), its anti-inflammatory for treating acute attacks of hereditary angioedema (HAE), in the mammary glands of transgenic rabbits (e.g., Rhucin) or cattle, then purifies the protein in milk.
According to Pharming, these methods are not only significantly faster and more cost-effective than manufacturing proteins in optimised cell cultures, they also yield better-quality and safer therapeutic products for medical or nutraceutical applications.
A single dairy can produce up to 10,000L of milk, the company notes, adding: " With expression levels of recombinant proteins in the milk of transgenic animals in the range of 1-10g/L, only a limited number of cows is enough to meet market demands for many medical applications ".
Pharming runs a state-of-the art cattle facility, Vienna Pharms, in Wisconsin, US that can house up to 80 transgenic calves.
Whereas 'Herman', the world's first transgenic bull, was generated through microinjection, Pharming uses nuclear transfer, which involves importing transgenic DNA into female bovine cells.
The nuclei of the transfected cells are injected into matured oocytes from which the original DNA has been removed.
The transgenic embryos are then transferred to foster mothers for development into transgenic calves.
This method substantially reduces the time needed for product development, as production herds are established directly, bypassing the conventional breeding process, Pharming points out.
As little as 15 months after establishing the first pregnancies, significant quantities of milk can be obtained through lactation induction to initiate preclinical product assessment, it says.
Large-scale production of calving-induced milk can begin after about 33 months.
Pharming hit a snag with its Rhucin development programme last December when the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMEA) adopted a negative opinion on the EU-wide approval application for Rhucin in HAE.
According to Pharming, the CHMP " was not reassured that there was sufficient evidence to confirm the benefits of Rhucin in laryngeal sub-mucosal attacks [of HEA], or how safe and effective the medicine is when given to a patient more than once ".
At that point, Rhucin had been administered more than 150 times to human subjects, several of whom received five or more doses of the drug, the company said.
It acknowledged that, with HAE being a rare, orphan disease, the number of patients treated in clinical programmes was relatively low.
Nonetheless, Pharming insisted, the quality of the product and the " clear " efficacy data generated from a placebo-controlled European trial - which last year was halted early for methodological and ethical reasons - " suggest that Rhucin is an advance in the many markets of Europe where no product [for HAE] has been approved to date ".
Pharming has asked for a re-examination of the CHMP's negative opinion, submitting detailed grounds for this request last month.
A final decision on the EU approval application for Rhucin is expected during the first half of 2008.