Interpretation of Pfizer's December 2021 Important Product Class Patents and Patents Related to Paxlovid Drugs: This report provides PFIZER's newly disclosed important product class invention patents in December 2021, and focuses on its newly obtained US FDA emergency use authorization for paxlovid drug related patents WO2021250648A1, and found Pardes through analysis Biosciences has fully disclosed the general formula structure and substituent conditions of Pfizer's compound in the description of patent US11124497B1.
table of contents
First, Pfizer urgently authorized the use of the drug Paxlovid related patent in-depth analysis
1. Interpretation of Pfizer's 3CL protease inhibitor drug Paxlovid patent WO2021250648A1
2. Pardes Biosciences and Paxlovid's patent interpretation of compounds with similar structures
3. Nankai University and the Shanghai Institute of Materia Medica of the Chinese Academy of Sciences have disclosed compound formulas similar in structure to Paxlovid
4. List of important patents for anti-new coronavirus 3CL protease inhibitors in the past 2 years
2. Pfizer disclosed patents for other important products in December
In December 2021, Pfizer was disclosed worldwide in 42 patents, including 10 US patents, 9 WO patents, 7 EP disclosures, and other disclosed countries/regions including China, Spain and India. Its patent contents mainly include nitrile-containing compounds that inhibit or block coronavirus (3CL protease inhibitors), IL15 variants, GLP1R agonists, Janus kinase inhibitory compounds, TL1A antibodies for inflammatory bowel disease, monoclonal antibodies against anticoagulant factor XIA, BCMA such as PF-06863135 and anti-PD-L1 antibodies for cancer, new immunogenic compositions for pneumococcal vaccines, Lorlatinib Maleate crystal form, Aminopyrimidinyl compounds as JAK inhibitors, etc.
From 2020 to 2021, there are many patents at home and abroad related to 3CL protease inhibitors against the coronavirus, among which important applicants in this field include Nankai University and the Shanghai Institute of Materia Medica of the Chinese Academy of Sciences.
Among the patents that Pfizer received in December 2021, the most noteworthy patent is WO2021250648A1 (Nitrile-Containing Antiviral Compounds), which deals with a nitrile-containing compound that can inhibit or prevent the replication of coronaviruses such as SARS-CoV-2, which is a 3CL protease inhibitor, and the patent has a total of 4 priority rights, all U.S. patents. The earliest priority date is U.S. Patent 63 / 073,982 of September 3, 2020.
The compound disclosed in the patent protects Nirmatrelvir (PF-07321332), one of the main ingredients in Pfizer's oral anti-coronavirus drug Paxlovid, which was granted by Pfizer on December 22, 2021 under the U.S. FDA Emergency Use Authorization (EUA), namely compound (1R, 2S, 5S)-N-{{(1S)-1-Cyano-2-[(3S)-2-oxopyrrolidin-3-yl]ethyl}- 6,6-dimethyl-3-[3-methyl-N-(trifluoroacetyl)-L-valyl]-3-azabicyclo[3.1.0] hexane-2-carboxamide (structural formula shown in Figure 1 below):
▲Figure 1 The structure and related information of PF-07321332 disclosed in patent WO2021250648A1
In the patent, claim 1 first claims protection of the structure of the nitrile-containing Marcus structural compound as shown in FIG. 2 below.
▲Figure 2 Compound Marcus structure disclosed in patent WO2021250648A1
The patent discloses in the specification of the compound Nirmatrelvir associated with the crystalline form and crystalline solids, as well as an amorphous structure, methyl tert-butyl solvate (compound E62-E66 in the patent), and disclosed in Example 13 the preparation process of the compound (FIG. 3 below), and discloses the preparation process of its methyl tert-butyl solvate. At the same time, the patent claims to protect the maximum oral dose range of 10mg-1500mg.
▲Fig. 3 Patent WO2021250648A1 discloses the preparation process of compound PF-07321332
The reason why Pfizer was able to quickly develop the compound to treat the new crown was that when the SARS outbreak occurred in 2002, combined with earlier scientific research findings, it began to design a 3CL protease inhibitor of the SARS coronavirus and obtained the drug-ready compound PF-00835231. But then the SARS outbreak ended in 2003, so Pfizer stopped research and development of the drug.
Pfizer filed a patent application in 2005 for this compound and its preparation (WO/2005/113580).
In the outbreak of the new crown in 2020, because the sequence of the 3CL protease required for replication of the new coronavirus and its earlier study of the SARS coronavirus was 100% the same at the catalytic site of protein cleavage, Pfizer optimized the compound on the basis of the PF-00835231 compound, and finally obtained a compound with satisfactory permeability and oral utilization such as cyano group PF-07321332 through the introduction of cyanide.
By searching for 3CL protease inhibitors for antiviral patents, it was found that Pardes Biosciences Company had 2 granted patents, applied for protection of proteases used for antivirals such as 3C- or 3CL cysteine protease inhibitors, patent disclosure and claimed protection as shown in Figure 4 (US11174231B1, authorized on November 16, 2021) and Figure 5 below (US11124497B1, authorized on September 21, 2021) The structure of the compound shown. The earliest priority right for the patent is April 17, 2020.
Figure 4 Pardes Biosciences patent US11174231B1 disclosed compound structure general formula
Figure 5 Pardes Biosciences Patent US11124497B1 disclosed compound structure general formula
Comparing the structure of the drug PF-07321332 developed by Pfizer, Pardes Biosciences granted patent US11124497B1 disclosed the compound general formula and its independent claim 1 description of the variable substituent (FIG. 5), there is a large structural similarity between the two, and the general formula structure and substituent conditions of the Pfizer compound are disclosed in the description of the patent (Fig. 6 below);
However, Pardes Biosciences disclosed in the patent more than 700 specific compounds and 42 compound preparation embodiments, there is no compound consistent with the structure of Pfizer compound.
Fig. 6 Pardes Biosciences Patent US11124497B1 discloses a structural general formula and substituent most similar to the structure of compound PF-07321332
Founded in early 2020, Pardes Biosciences is a biopharmaceutical company dedicated to researching drug treatments for COVID-19.
The company's 3CL protease inhibitors are used in anti-COVID-19 research results, most likely thanks to its chief scientific officer, Dr. Lee Arnold, who has worked for pharmaceutical companies such as Pfizer, and through patent searches, it can be found that Pfizer has applied for a total of 102 (24 patent families) inventors including Lee Arnold, filed for 1994-2017, and its patents are mainly heterocyclic compounds, quinoline or pyrimidine derivatives.
Other important innovative research subjects in mainland China with similar structures to this compound are mainly the Shanghai Institute of Materia Medica of the Chinese Academy of Sciences and Nankai University.
Among them, the patent CN201511030933.6 disclosed compound structure disclosed in 2015 by the Shanghai Institute of Materia Medica of the Chinese Academy of Sciences in cooperation with the School of Biochemistry of the University of Lübeck in Germany is shown in Figure 7 below, although the focus is on enteroviral protease inhibitors, but in the patent disclosed that it has inhibitory activity against coronavirus (SARS) master protease;
Patent CN201810903062.1, patent applied in collaboration with Fudan University, discloses the application areas of the compound for the treatment or prevention of diseases related to coronavirus or Ebola virus.
Figure 7 The general formula of a compound similar to the structure of PF-07321332 in the patent application of the Shanghai Institute of Materia Medica of the Chinese Academy of Sciences
Nankai University has more patents for research on compounds of similar structures (figure 8 below), but its compounds are mainly used for enterovirus 71, which is mainly in cooperation with Tsinghua University.
Figure 8 The general formula of a compound similar to the structure of PF-07321332 in the patent application of Nankai University
Through patent analysis, in addition to Pfizer and Pardes Biosciences, the 3CL protease inhibitors for the new coronavirus in 2020-2021 also include the Shanghai Institute of Materia Medica of the Chinese Academy of Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai Jiao Tong University, Dompe Farmaceutici, Nlc Pharma Ltd, etc., of which the main patents of the above applicants are shown in Table 1 below.
▼Table 1 List of major patents for the research and development of 3CL protease inhibition against the new coronavirus in 2020-2021
Other important patents disclosed by Pfizer in December include the IL15 variant, the GLP1R agonist, and the Janus kinase inhibitory compound, as shown in Table 2.
▼Table 2 Pfizer's important product patent information in December
Source: Dawei Intellectual Property
Edit: Sharon