How does Pfizer do the patent layout?Knowing these points is important

How does Pfizer do the patent layout? Knowing these points is important

Source: Yaozhi.com/ Williamxiang

Make drug creation easier.

Recently, as the FDA approved the world's first TYK2 inhibitor and the eighth JAK kinase inhibitor in China, the JAK kinase inhibitor entered the public's vision again, and the attention continued to rise. There are already many articles that introduce JAK kinase suppression and mechanisms, as well as listing and research products, and I wo n’t repeat it about it. This article will use the "Universe Factory" Pfizer as an entry to analyze and explore its patent application layout of the Jak kinase inhibitor.

The key enzymes of Pfizer JAK Kinase inhibitory compound patents involve JAK1, JAK3 and Tyk2. The parent nuclear has a certain selectivity to JAK1 and JAK3, indicating that when the parent nucleus is the same, replacement of the base will affect its selectivity.

According to the general strategy of Pfizer's crystal patent layout, and considering the relatively late application time for Pfizer Crystal patent, it can be speculated that Pfizer is developing these theme compounds as preferred compounds as preferred below. It is worth focusing on attention. Essence Please see below.

Compound patent

1. Overall sorting out

Note:

A patent open number/announcement number is included in the priority order: CN ... B/C (authorized announcement)> cn ... A (application public)> us ... bx> ep ... bx> us ... AX> EP ... BX> Others, in a strict sense, only those who apply for disclosure should be called "patent application", which is collectively called "patent" in this article;

The B instructions only qualitatively disclose the inhibitory activity of the compound to enzymes, and the quantitative data is not disclosed.

C's compound patent of Tarvarto;

D only disclosed the IC50 of the two compounds to JAK1 ~ 3 and the IC50 of Tyk2 by 1 compound;

E only discloses the inhibitory effect of 4 compounds on T cell proliferation;

F is the compound of AbroCitinib. The compound disclosed on JAK1, JAK2, JAK3 and Tyk2's IC50 values ​​(ranking) in turn is 29 (30.5), 803 (29),> 10000, 1250 (24) nm;

G only discloses the inhibitory activity of the four compounds including Abroctinib to various enzymes;

NSID = Not Specified in Description, that is, it is not clear in the manual

Second, a single patent preferred compound relationship relationship relationship relationship

CN102131812B only discloses the inhibitory activity of two compounds to each JAK kinase, as shown in the table below:

Note:*represents the key enzyme of the patent.

CN102574860A disclosed the inhibitory activity of 141 compounds to JAK1 ~ JAK3. The preferred compounds of different indicators are shown in the table below:

US8372854B2 disclosed the inhibitory activity of 51 compounds to JAK1 ~ 3. The preferred compounds of different indicators are shown in the table below:

Note:

A The digital drawn in each structure represents the embodiment number of the compound in the relevant patent.

CN102822177A only disclosed the IC50 of 4 compounds to the proliferation of T cells. As a result, the following table is shown:

CN105008362B disclosed the inhibitory activity of 42 compounds to JAK1 ~ 3 and TYK2. The preferred compounds of different indicators are shown in the table below:

It should be pointed out that the patent is the compound of Abrocitinib. The compound disclosed on JAK1, JAK2, JAK3 and Tyk2's IC50 values ​​(ranking) in turn is 29 (30.5), 803 (29),> 10000, 1250 (24) nm.

CN106061973B disclosed the inhibitory activity of 329 compounds to JAK3, of which the five compounds of the best inhibitory activity of JAK3 (IC50 <0.1 ~ 0.1nm) when the ATP concentration is 4 μm is shown below.

The patent also disclosed multiple other compounds for the IC50 = 0.1nm of JAK3 when the ATP concentration is 4 μm. The two compounds with the lowest IC50 value of JAK3 when the ATP concentration is 1mm is included.

As mentioned earlier, the patent disclosed that most of the compounds on the IC50 value of JAK3 when the ATP concentration was 1mm, with a minimum value of 3.4nm. This article did not describe it in detail.

CN106459048A disclosed the inhibitory activity of 169 compounds to JAK1 ~ 3 and TYK2. The preferred compounds of different indicators are shown in the table below:

US10966980B2 disclosed the inhibitory activity of 120 compounds to JAK1 ~ 3 and TYK2. The preferred compounds of different indicators are shown in the table below:

CN107074867B disclosed the inhibitory activity of 117 compounds to JAK1 ~ 3 and TYK2. The preferred compounds of different indicators are shown in the table below:

The US10703756B2 disclosed the inhibitory activity of more than 300 compounds to JAK3, and the 5 compounds with the lowest IC50 value (0.124 ~ 0.179 nm) are shown below. CN109071546B disclosed the inhibitory activity of 37 compounds to JAK1 ~ 3 and TYK2. The preferred compounds of different indicators are shown in the table below:

US11254668B2 disclosed the inhibitory activity of 481 compounds to JAK1 ~ 3 and TYK2. The preferred compounds of different indicators are shown in the table below:

It should be pointed out that although the title of the present invention is piper and [1,5-A] pyrazine-like compounds, the structure of the compounds disclosed in the claims and instructions The structure of the optimized compounds is raviolin or pyrine.

WO2021240356A1 disclosed the inhibitory activity of 4 compounds to JAK1 ~ 3 and TYK2. As a result, as shown in the following table:

Crystal patent

According to the general strategy of the crystal patent layout, and considering the relatively late application time of the crystal patent, it can be speculated that Pfizer is or about to further develop the theme compounds as a preferred compound, which is worthy of attention.

In addition, similar to Abroctinib, the theme compounds in the crystal patent are not the best enzyme inhibitory activity in the patent of the patent of the corresponding compound, which shows that in addition to enzyme suppression activity, there are other important considerations, such as selectivity.

Conclusion

Selective-Structural Maternal Auction Analysis

As can be seen above, the key enzymes of Pfizer's JAK Kinase inhibitory compound patent involve JAK1, JAK3 and TYK2. -D] Piopidine is the most, and the parent nuclear has a certain selectivity to JAK1 and JAK3, indicating that when the parent nucleus is the same, the substitution base will affect its selectivity.

PS: Due to the limited energy of the author, there must be defects in this article. The main manifestations are that patent retrieval cannot guarantee 100%inspection. This article does not selective and preferably sort in compounds. The author will improve in subsequent articles. Interested friends continue to pay attention to, and welcome to forward discussions and comments.

- END -