MF59 adjuvant patents

MF59 is the subject of a large patent family titled "Adjuvant formulation comprising a submicron oil droplet emulsion".  Patents have been granted in Canada, European countries of Austria, Germany, Denmark, Spain, Greece, Hungary, Ireland, Portugal - Hong Kong, Japan and the United States.  An application is also pending in the U.S.  Between the European patents and United States patents, broader claims have issued in Europe, although claims broader than already issued in the U.S. are being pursued. 

The lead claim in EP 0 399 843 B recites an adjuvant composition comprising:

• a metabolizable oil, and
• an emulsifying agent

in which the oil and emulsifying agent are in the form of an oil-in-water emulsion;

the oil droplets in the emulsion are less than 1 micrometer in diameter;and

the composition does not contain a block copolymer.

The lead claim (Claim 1) broadly encompasses oil-in-water emulsions as long as the oil is metabolizable, the oil droplets are sub-micron in size, and a block copolymer is not in the emulsion.¹  As such, this claim covers many compositions, of which MF59 is but one.  The particular formula of MF59 (squalene, polyoxyethylene sorbitan monooleate and sorbitan trioleate) isn't claimed until claim 8 (The composition of the lead claim wherein the emulsifying agent comprises a polyoxyethylene sorbitan, mono-, di-, or triester or a sorbitan mono-, di- or triester.).  The intervening claims recite particulars about the oil - an animal oil, an unsaturated hydrocaron, a terpenoid, a vegetable oil, the oil is 0.5 to 20% by volume; and about the emulsifying agent - comprises a non-ionic detergent. 

The two U.S. patents have much narrower claims.  US 6,299,884 B claims methods of stimulating an immune response by administering an antigen and adjuvant consisting essentially of:

(i) 0.5% to 20% v/v of a metabolizable oil, and

(ii) 0.01% to 2.5% w/w of an emulsifying agent,

in which substantially all the oil droplets of the oil-in-water emulsion are about 100 nm to less then 500 nm diameter,

and the composition does not contain either any polyoxypropylene-polyoxyethylene block copolymer or muramyl peptide. 

US 6,451,325 claims an adjuvant composition consisting essentially of:

(i) 0.5% to 15% v/v of a metabolizable oil,

(ii) 0.01% to 2.5% w/w of an emulsifying agent, and

(iii) an antigen

in which substantially all the oil droplets of the oil-in-water emulsion are about 100 nm to less then 500 nm diameter,

the antigen is not present in the internal phase of the adjuvant composition, and

the composition does not contain any polyoxypropylene-polyoxyethylene block copolymer.

"Consisting essentially of" carries a special meaning in U.S. patent claims.  The transitional phrase "consisting essentially of" limits the scope of a claim to the specified materials or steps "and those that do not materially affect the basic and novel characteristic(s)" of the claimed invention.  In other words, some additional ingredients will still render a composition infringing, but not if the ingredients considerably alter the essential quality of the claimed invention.  There isn't a bright line rule for someone to know which additional ingredients will allow the compostion to evade the claims.  It needs to be evaluated on a case-by-case basis and a showing of evidence of alterations will likely be required to sway a court to a finding of non-infringement. 

Claims being pursued in US 10/246,195 currently (as of March 2008) recite a composition comprising:

(i) an adjuvant comprising

4-5% v/v squalene and

an emulsifying agent consisting essentially of polyoxyethylenesorbitan monooleate and sorbitan trioleate,
in which the total amount of the sorbitan ingredients is about 1% w/w;
substantially all of the oil droplets of the oil-in-water emulsions are less then 1 micron diameter; and
there isn't any polyoxyproplylene-polyoxyethylene block copolymer;

(ii) an antigenic substance

in which the antigenic substance is from a virus, a bacterium or a parasite; and
the antigenic substance is not present in the internal phase of the adjuvant composition. 

Even though the United States Patent Office is often accused of issuing too broad claims, in this case, it is the European Patent Office that has issued very broad claims.  All the U.S. claims - patented or pending - are a fair bit narrower in scope.

1 - In a series of patents, all of which are now expired, Syntex had patented an adjuvant composition that contained an immunopotentiating amount of an immunostimulating glycopeptide, a polyoxypropylene-polyoxyethylene block polymer, a glycol ether-based surfactant, and, optionally, a metabolizable non-toxic oil.  These patents are likely why a block co-polymer is excluded from the MF59 claims.  Note that some of Syntex patents directed to similar subject matter are still in force.

The information contained in this page was believed to be correct at the time it was collated. New patents and patent applications, altered status of patents, and case law may have resulted in changes in the landscape. CAMBIA makes no warranty that it is correct or up to date at this time and accepts no liability for any use that might be made of it. Corrections or updates to the information are welcome. Please send an email to info@bios.net.

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