Drafting crystal patent claims in China: the implications of divergent approaches

The crystal form of an active pharmaceutical ingredient (API) is important for drug development, because APIs are typically developed as a solid dosage form, which can exist as a wide range of crystalline solids. The crystal form often dictates key properties of drug formulation, including solubility, stability, and processability. In the pharmaceutical industry, X-ray powder diffraction (XRPD) is a testing method widely employed to definitively distinguish different crystal forms of the same compound. It has therefore become a common practice to define crystal form claims by XRPD parameters.

In practice, the CNIPA, in granting crystal patents, allows divergent approaches in defining the subject matter of crystal form claims. However, as indicated in several publicly available invalidation cases, the divergence is not without ramifications, as different approaches may have varying implications for the interpretation of the protection scope of the claims, and even the assessment of novelty.

The divergent drafting approaches employed by patentees are exemplified by two recently granted crystal patents, as analysed below.

CN109379891B, which is entitled 'Polymorphs of kallikrein inhibitors’, has a granted claim 1 that reads: “A solid form of N-[(3-fluoro-4-methoxypyridin-2-yl)methyl]-3-(methoxymethyl)-1-({4-[(2-oxopyridin-1-yl)methyl]phenyl}methyl)pyrazole-4-carboxamide, which exhibits at least the following characteristic X-ray powder diffraction peaks at […]”(emphasis added).

CN110372670B, which is entitled ‘Therapeutically active compounds and their methods of use’, has a granted claim 1 that reads: “An isolated crystalline form of 2-methyl-1-[(4-[6-(trifluoromethyl)pyridin-2-yl]-6-{[2-(trifluoromethyl)pyridin-4-yl]amino}-1,3,5-triazin-2-yl)amino]propan-2-ol methanesulfonate, wherein the isolated crystalline form is form 3, characterised in having the peaks of X-ray powder diffraction pattern at […]” (emphasis added).

The difference between the two examples is that example 2 explicitly defines the protected subject matter as a crystal form of “form 3”, while example 1 only defines “a solid form” of the compound. In fact, the description of example 1 also discloses multiple crystal forms of the compound, which are named as forms 1–18, wherein the definition of claim 1 is consistent with form 1 in terms of XRPD characteristic peak positions. However, contrary to the drafting approach of example 2, example 1 does not define the name of the crystal form, “form 1”, in the claims.

In the substantial examination proceeding, both claims were allowed by the CNIPA examiners. However, the choice the patentees made in the drafting process may have unexpected implications when a patent’s validity is scrutinised in invalidation proceedings, as illustrated by two invalidation decisions below.

Regarding patent ZL201410302945.9, which is entitled ‘A Trifluridine compound and the pharmaceutical composition thereof’, the claims examined in invalidation decision No. 50128 are:

1. “A Trifluridine compound as shown in Formula (I), characterised in that the said Trifluridine compound is in a crystalline form with its XRPD diagram having characteristic peaks at […]”;

2. “The Trifluridine compound of Claim 1, characterised in having the XRPD diagram as shown in Fig.1”; and

3. “[…]”.

Analysing from the perspective of formality, the claims of the patent have the following features:

The subject matter is defined as the crystalline form of the compound, without specifying the name of the crystal form, using the same drafting approach of example 1; and

Claim 1 defines the XRPD peak positions, and dependent claim 2 defines the characteristic of the entire XRPD diagram.

In this case, the petitioner argued that the patent lacked novelty over the crystal form disclosed by the prior art. Through comparison, it was found that the crystal form of Trifluridine as disclosed by the prior art has all the characteristic peaks as defined by claim 1, while the relative intensities of the characteristic peaks differ markedly between the prior art and figure 1, as referred to in claim 2. Thus, the collegiate panel held that claim 1 was devoid of novelty and should be invalidated, while claim 2 possessed novelty and was sustained.

This case is intriguing as it demonstrates a possibility that in certain circumstances, the protection scope of a crystal patent claim defined by an XRPD diagram may not equate to the scope as defined by the positions of some peaks selected from the XRPD diagram. In assessing the novelty of claim 1, the invalidation decision opined that “[c]laim 1 only defines (the position of) partial characteristic peaks without stating the relative intensities, peak numbers, or the XRPD diagram. This indicates that the patentee intends to acquire a broader scope of protection, which is not limited to a specific crystal product actually prepared by the embodiments” (emphasis added).

Therefore, such drafting approach could prompt the examiner to separately assess the protection scope as defined by the XRPD diagram and by the peak positions, which might lead to contradictory findings of validity.

The case below further illustrates that the examination criteria may change significantly when the claims are defined in a different manner.

Regarding patent ZL201510038935.3, which is entitled ‘Crystal Form of 7-Ethyl-10-Hydroxycamptothecin and the Preparation Method and Application thereof’, the claims examined in invalidation decision No. 580492 are:

1. “A crystal form II of 7-ethyl-10-hydroxycamptothecin, characterised in that it is irradiated with Cu-Kα, and the XRPD represented by a 2θ value has characteristic peaks at a diffraction angle of […]”;

2. “A crystal form II of 7-ethyl-10-hydroxycamptothecin, characterised in that it is tested with [the] Cu-Kα spectrum and shows an XRPD diagram as [illustrated in] Figure 1”;

3. “A crystal form II of 7-ethyl-10-hydroxycamptothecin, characterised in that it has an infrared spectrum with bands at […]”; and

4. “[…]”.

This patent and the patent in case 1 use both XRPD characteristic peak positions and an XRPD diagram to define the protection scope of the crystal patent. The difference is that the former explicitly limits the specific “crystal form II” in the subject matter of the claims, using the same drafting approach of example 2.

In the invalidation procedure, the patentee requested an amendment of the claims through incorporating the technical feature of the original claim 2 (which reads “it is tested with [the] Cu-Kα spectrum and shows an XRPD diagram as [illustrated in] Figure 1”) into claim 3.

The petitioner challenged the legality of the amendment, arguing that claims 1–3 belonged to different technical solutions, as the description failed to specify which embodiment of the patent produced the crystal of figure 1. Thus, the merged claims formed a new technical solution that exceeded the disclosure of the original application.

However, the panel was not convinced. It held that the original claims 1–3 protected the same technical solution, as “the subject matter of Claims 1-3 have been clearly defined as crystal form II”, and further considering the disclosure of the patent description, the definitions of the original claims 1–3 were directed to the technical features of the same crystal form II. Therefore, the panel determined that this amendment did not exceed the scope of the original application. In reviewing the novelty, the panel also comprehensively combined all the technical features of the XRPD characteristic peaks positions, the XRPD diagram, and the infrared spectrum defined in claims 1–3 as an identical technical solution, and ultimately concluded that claims 1–3 were novel.

In this case, the panel determined that the protection scope of the claims as limited by the XRPD characteristic peak positions and by the XRPD diagram are substantially the same, which seems to contradict the criteria employed in case 1.

The panel made the following clarification in the decision: “For the inventions of crystal forms of organic compounds, in general, if a claim only defines partial characteristic peaks without specifying the crystal form, it indicates that the patentee intends to obtain a relatively wide protection scope which is not limited to the specific crystal form actually prepared in the embodiments. The protection scope of such a claim should be different from that of a claim as limited by the full XRPD diagram. However, as mentioned above, under the premise that Claims 1–3 have clearly defined their subject matter as crystal form II, the technical solutions of Claims 1-3 should be perceived as characterising the same crystal form with different parameter features” (emphases added).

Therefore, it was the difference in the wording of the subject matter in cases 1 and 2 that prompted the panel to make divergent conclusions in their validity assessment.

The above cases seem to attest the following findings in the CNIPA’s current examination practice: in the absence of a specified crystal form in the subject matter of claims, the scope defined by partial characteristic peak positions may be interpreted more broadly, rather than being limited to the specific crystal form actually prepared in the embodiments. Conversely, if the subject matter is explicitly limited to a specific crystal form, the protection scope may be interpreted as limited to the crystal form obtained in the description.

There is a pitfall, though, if patentees intend to leverage such a finding in tactically broadening the protection scope of their crystal form patent.

Where the protection scope of the claim covers crystal forms that are not actually prepared according to the patent description, the validity of the technical solutions would be questioned by the examiners, as they cannot be supported by the description. Therefore, even if the subject matter is drafted in such a manner that it is not limited to a specific crystal form, this drafting tactic is likely to increase the risk of patent invalidity, rather than broadening the protection scope of the patent.

In short, to err on the safe side, it is advisable that patentees limit the subject matter to a specific crystal form so that they would be able to fend off validity challenges by interpreting the scope of protection in a more pragmatic manner.