Proposed Revisions to the Canadian Patent Office’s Examination Guidelines on Pharmaceutical Solid Forms

The Canadian Patent Office (CPO) is seeking comments on its proposed revisions to Chapter 17 of the Manual of Patent Office Practice (MOPOP) as it relates to pharmaceutical solid forms (namely, polymorphs, salts, hydrates, solvates, desolvates and co-crystals).  In this post, we will examine various section of this amended chapter in detail.

Considerations Respecting Anticipation and Obviousness (Chapter 17.08.01)

This section of amended Chapter 17 describes the considerations to be used in assessing anticipation and obviousness of pharmaceutical solid forms.  According to this section, where a particular crystalline form (such as a polymorph) of a small chemical molecule has not been disclosed and enabled in the prior art, either explicitly or inherently, a claim to that crystalline form is considered to be novel and satisfy subsection 28.2(1) of the Canadian Patent Act (Patent Act).  However, if a polymorph is disclosed and enabled in the prior art, a claim encompassing that polymorph is considered to be anticipated.  Thus, a known polymorph will not be novel simply by making it dependent on a new process.  Nonetheless, a claim to a process used to prepare a polymorph may be novel if it can be distinguished over the prior art.

When assessing obviousness of a new crystalline form, the chapter notes that one factor to be considered is the process by which the new form is produced.  Inventiveness may be acknowledged for a form that can only be produced using an inventive process (such a process is considered to go beyond the mere application of common general knowledge and routine experimentation).

Nevertheless, the chapter further states that even if a process used to prepare a new solid form relies on basic crystallization techniques that are standard in the field, the solid form may still be non-obviousness.  Specifically, inventiveness may be acknowledged if the originally-filed application discloses that the form provides an unexpected benefit, such as a beneficial physicochemical property that is attributable to the form itself.  Specifically, the chapter further notes that:

Only benefits disclosed in the originally-filed application will be taken into account during an obviousness assessment.  The disclosure of the benefit may be either explicit (e.g., direct statements) or implicit (e.g. supportive data provided in the application).  In a patent application the most persuasive disclosure is one that provides data comparing the form of the invention to the prior art form (or all of the closest prior art forms when more than one exist) and confirms that there is a significant difference or improvement in one or more physicochemical properties compared to the prior art form(s) of the same chemical molecule.  Where the specification comprises statements indicating a solid form ‘may’ have a particular benefit or ‘has at least one’ benefit selected from a list of benefits (without clearly stating which it has), this amounts to an inexplicit indication of potential benefit.  Unless the benefit would be implicit from data provided in the application, such statements would not be considered during an obviousness assessment.  Likewise, a benefit that is recognized subsequent to the filing of the original application would be given no weight in the assessment.

It is important to note that the person skilled in the art would generally expect or predict that a crystalline form will have certain benefits over an amorphous form of the same small chemical molecule, including easier isolating, purifying, drying, and in batch processes, easier handling and formulating.  However, such expected are generally not sufficient, when taken alone, to support a finding of non-obviousness.

Considerations Respecting Utility (Chapter 17.08.02)

This portion of amended Chapter 17 states that although the utility of a polymorph does not need to be expressly set out in the application, the subject matter must have utility.  Moreover, a person skilled in the art would reasonably expect that polymorphs of a known small chemical molecule that have a previously established utility (either pharmacological or therapeutic) would also possess the same activity.  In such cases, because the utility of the polymorph will generally be self-evident to the skilled person, the utility requirement of section 2 of the Patent Act would be satisfied.

A utility defect will be made if the specification is silent regarding the utility of the claimed polymorph and the utility of other known forms of the same small chemical molecule are neither disclosed in the specification or common general knowledge to a skilled person in the art.

In instances where the claimed crystal form has a utility different from other known form(s) of the small chemical molecule, the utility must be established by demonstration or sound prediction.  However, if the utility relies on a physicochemical property that was not established and could not have been predicted, then the utility of the subject-matter of the invention cannot be established by sound prediction.  Specifically, this portion of the chapter states, “[R]ecall that the specific physicochemical properties of a particular crystalline form are generally considered as unpredictable since the crystal form must be prepared and tested before its properties can be ascertained (see 17.08.01). Given that such properties cannot be predicted and would not be implicit to the skilled person, in order to establish utility the applicant must be in a position to show that the property associated with the utility was demonstrated no later than the filing date of the application.”

Defining a polymorph in the claims (Chapter 17.08.03)

This portion of amended Chapter 17 states that with respect to claiming polymorphs, that the polymorph must be defined in terms of physical characterization data and/or physicochemical properties that are specific to its solid state structure and which serve to distinctly and explicitly distinguish it from all other forms of that molecule or in terms of the process by which it is made.

Polymorphs can be defined in a claim by: (1) the physical parameters relevant to its particular crystal structure; (2) spectral analysis parameters (such as X-ray powder diffraction (XRPD) pattern, Raman spectrum and/or solid-state nuclear magnetic resonance (NMR)); or (3) parameters associated with methods of thermal analysis (such as infrared (IR) absorption, differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), melting point or combinations thereof).  Polymorphs should not be defined by an internal designation (such as Form I, polymorph B, etc.), molecular formula or chemical name.

Examples (Chapter 17.08.05)

This portion of amended Chapter 17 provides two hypothetical examples involving claiming strategies for polymorphs and the application of the anticipation, obviousness and utility requirements discussed previously.  These examples are very useful from a practical perspective in understanding how the CPO will examine these claims.

Considerations relating to particular solid forms (Chapter 17.08.06)

This portion of amended Chapter 17 notes that the patentability of pharmaceutical salts, hydrates, solvates, desolvates and co-crystals involve the same considerations as those described earlier with respect to polymorphs.

Salts (Chapter 17.08.06a)

With respect to assessing whether claims to a novel salt are inventive, this portion of amended Chapter 17 notes that the process used to prepare a salt and any unexpected beneficial properties of the salt may be informative.  Where the originally-filed application discloses that a salt can only be produced using an inventive process that goes beyond routine methodologies or that the salt has a beneficial property that is unexpected, the claimed salt is inventive and complies with section 28.3 of the Patent Act.  Additionally, a person skilled in the art would reasonably expect that salts of known small chemical molecule having a previously established utility would also possess the same utility despite incorporation of a counterion in its structure.

In terms of defining a salt in the claims, inclusion of the counterion in the structure of the molecule is often sufficient to satisfy the requirements of subsection 27(4) of the Patent Act (such as, for example, by claiming “A besylate salt of compound of Formula (I)…”).  In cases where the claim is directed to a specific polymorph of a salt, the physical parameters relevant to the polymorph’s particular crystal structure must also be defined in order to satisfy the requirements of subsection 27(4) of the Patent Act.

Hydrates, solvates and desolvates (Chapter 17.08.06b)

With respect to assessing whether claims to a novel solvate or desolvate are inventive, the amended chapter notes that the process used for the preparation and any unexpected benefits of the particular entity may be informative.  As with novel salts, where the originally-filed application discloses that a solvate or desolvate can only be produced using an inventive process that goes beyond routine methodologies or that the solvate or desolvate crystalline form has a beneficial property that is unexpected, the claimed solvate or desolvate is inventive and complies with section 28.3 of the Patent Act.  Additionally, a person skilled in the art would reasonably expect that solvates and desolvates of known small chemical molecule having a previously established utility would also possess the same utility despite incorporation of a solvent into the crystal lattice (solvate) or the removal of a solvate form the solvated form (desolvate).

In terms of defining a solvate in the claims, inclusion of the number of solvent molecules per small chemical molecule is often sufficient to satisfy the requirements of subsection 27(4) of the Patent Act (such as, for example, by claiming, “A dihydrate of the compound of formula (I)”).   In cases where the claim is directed to a specific polymorph of a solvate, the physical parameters relevant to the polymorph’s particular crystal structure must also be defined in order to satisfy the requirements of subsection 27(4) of the Patent Act.

With respect to defining a desolvate in the claims, inclusion of the physical parameters relevant to its particular crystal structure are often sufficient to satisfy the requirements of subsection 27(4) of the Patent Act.

Co-crystals (Chapter 17.08.06c)

With respect to assessing whether claims to a novel co-crystal are inventive, as with salts, solvates and desolvates, the amended chapter notes that the process used for the preparation and any unexpected benefits of the particular co-crystal may be informative.  Specifically, the chapter notes that “[G]iven the state of the art and recognizing the extensive number of potential co-crystal formers that can be used, screening for co-crystals may involve an inventive process and co-crystals produced by such an inventive process would also be inventive”.  Additionally, a person skilled in the art would reasonably expect that co-crystals of known small chemical molecule having a previously established utility would also possess the same utility despite incorporation of a co-crystal in its structure.

In terms of defining a co-crystal in the claims, like polymorphs, inclusion of the relevant physical parameters to the particular crystal structure of the co-crystal are often sufficient to satisfy the requirements of subjection 27(4) of the Patent Act.

The deadline for submitting comments to CIPO on the above amended Chapter 17 is August 17, 2018.

This post was written by Lisa Mueller.

 

 

Author: Lisa L. Mueller

I am a Patent Attorney with Casimir Jones.

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