Patent Landscape Report on Ritonavir - WIPO

are cited by more than one other document in the innovation track. The documents in the orangeboxes help interrelating the documents describing prodrug forms of Ritonavir. Covalentlylinking Ritonavir to peptides, amino acids, or non-peptidic polymers such as variouspoly(alkylene) oxides appears to be a recurrent theme throughout the documents in the innovationtrack.WO9414436, assigned to Abbott Laboratories, is the first disclosure of Ritonavir. The ‘436document claims a broad Markush structure describing Ritonavir. This initial document onlyclaims a retroviral protease inhibitor and does not appear to have claims directed to prodrugforms of Ritonavir. Only one document describing a prodrug form of Ritonavir,WO10144869, cites the ‘436 document. The other documents may be related to the ‘436document by more than 6 backward citations, but do not directly reference the ‘436 document.WO10144869 is discussed in greater detail below in the paragraph discussing secondgeneration documents.The next documents in the innovation track, WO8500372 (Battelle Memorial Institute),WO9514016 (Merck), WO9404193 (Enzon Inc), do not describe prodrugs of Ritonavir, butare cited either directly or indirectly by more than one document describing prodrugs of Ritonavir.Thus, these documents connect the other documents in the innovation track and appearto be pivotal documents in the progression of Ritonavir prodrug technology. The ‘372document describes a biodegradable polypeptide in which drugs may be incorporated. Thepolypeptide is degraded slowly in the body allowing for the gradual release of drugs. Thedocument claims an esterified cyclic polypeptide including polyaspartate or polyglutamatethat may be used as a carrier for drugs. This document is indirectly related by four backwardcitations to US6765019 and WO03020200, which both describe prodrug forms of Ritonavirand are discussed below. The ‘372 document is important in the innovation track becausemany of the documents in the innovation track describe prodrugs of Ritonavir in which Ritonaviris covalently linked to polypeptides or amino acids. Some of the documents in the innovationtrack also suggest that covalently linking polypeptide or amino acid residues canenhance drug bioavailability. WO9514016 describes ester prodrugs of the HIV protease inhibitorL-735,524, now known as Indinavir. The prodrugs help improve the extended releaseproperties of the protease inhibitor and increase the solubility of the drug in the intestine.Document ‘016 is directly cited by FR2773994, WO9933815, US7662987, three first generationdocuments describing prodrug forms of Ritonavir. These documents are discussed ingreater detail below. The ‘016 document is important to the innovation track because it is theearliest document in the innovation track that demonstrates the ability to apply prodrug technologyto protease inhibitors. WO9404193 describes polymer based prodrugs comprisingdrugs covalently linked to polyalkylene oxides. The document suggests that the incorporationof covalently linked polyalkylene oxides is particularly useful for peptide therapeuticagents and functions to prolong the circulating life, improve solubility, and increase the pHstability of the drug. The document has broad independent claims to polypeptide or chemotherapeuticdrugs, but does not explicitly claim protease inhibitors or antiviral compounds.WO9404193 is directly cited by US6765019 and WO04005313 (these documents are discussedin greater detail below in the paragraph discussing first generation documents) andindirectly cited by WO10107831, WO07089745, and WO08098789 (these documents arediscussed in the paragraph describing third generation documents) by three or more backwardcitations. The ‘193 document is important in the innovation track because it presentsthe concept of covalently linking polyoxyalkylene oxides to therapeutic agents to produce