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Rise of the Improper Markush Grouping Rejection and Biomolecules

With the “improper Markush grouping” rejection, U.S. patent examiners may reject claims reciting various alternative polynucleotide or polypeptide sequences.  However, there is no per se rule that groupings of alternative sequences are improper, as subsequent decisions from the Patent Trial and Appeal Board (PTAB) have made explicit.

The Ninth Edition (rev. 8) of the Manual of Patent Examining Procedure (MPEP), published in 2018, formally revived the “improper Markush grouping” rejection, with the current version specifying:

A Markush claim may be rejected under judicially approved “improper Markush grouping” principles when the claim contains an improper grouping of alternatively useable members. A Markush claim contains an “improper Markush grouping” if either: (1) the members of the Markush group do not share a “single structural similarity” or (2) the members do not share a common use. Supplementary Guidelines at 7166 (citing In re Harnisch, 631 F.2d 716, 721-22, 206 USPQ 300, 305 (CCPA 1980)).  

MPEP, 9th ed., rev. 10, § 2117(II) (emphasis added)

Thus, overcoming a rejection under these “principles” requires a showing that every member has both a “structural similarity” and a “common use.”  The latter element is often satisfied by disclosure in the patent application itself describing the common use of a particular collection of alternatives.  It is the “structural similarity” element that may prove to be the sticking point with an examiner.  

Although the Federal Circuit has not taken up this issue since the rejection was formally revived in the MPEP, decisions by the PTAB offer some helpful insight.  

In Ex parte Buyyarapu (Appeal 2018-006665; Application No. 14/212,469), an examiner rejected a claim reciting “at least one marker that is linked to the RN resistance trait, the marker being selected from the group consisting of SEQ ID NOs: 58-62” as an improper Markush grouping.  Notably, the PTAB expressly repudiated the notion that mere sequence differences rendered a group per se improper, stating:

To the extent Examiner applied a bright-line rule that focused solely on the sequence differences without consideration of other structural similarities, that approach is incorrect. See Harnish, 631 F.2d at 722 (“[I]n determining the propriety of a Markush grouping the compounds must be considered as wholes and not broken down into elements or other components.”); see also MPEP § 706.03 (y)(IV).

The PTAB in Ex parte Buyyarapu went on to find a “structural similarity” by virtue of “their specific physical proximity to each other and overall location within [the] cotton genome,” and a “common use” as markers of plant resistance to a particular pest.

The PTAB reversed another improper Markush rejection in Ex parte Narva (Appeal 2018-006168, Application No. 14/577,811).  There, the rejected claim recited several enumerated sequences for inhibitory double-stranded RNAs.  The PTAB quoted the applicant’s position that “a single structural similarity does not require nucleotide sequence level granularity” and concluded that “[w]e agree with Appellants that the claimed Markush group is not improper.”  With regard to the “structural similarity,” the PTAB observed that “[t]he nucleic acid sequences recited in the rejected claims belong to the same recognized chemical class of polyribonucleotides that are hybridized in dsRNA molecules and encode ROP proteins.” The “common use” was in “silencing ROP proteins.”

These two cases highlight a measure of latitude in the nature of the “structural similarity” that may be deemed sufficient, including physical proximity in a genome, and encoding portions of homologous proteins.  Indeed, even where the alternatives do not belong to an “art-recognized class,” the grouping may still be considered proper if the alternatives share a common use that “flow[s] from the substantial structural feature.”  (Ex parte Buyyarapu, citing MPEP § 706.03(y)(II) (now restated in MPEP § 2117(II)(B)).

 

Takeaway:  Mere sequence differences among claimed alternative polynucleotides or polypeptides are not adequate basis to sustain an “improper Markush grouping” rejection.  However, rebutting such a rejection will require articulating some structural feature and use shared by members of the group.

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Authors

Marc T. Morley is recognized as one of San Diego's top IP lawyers. He works with Mintz clients to develop and implement effective intellectual property strategies. Marc also handles IP-related transactions and due diligence. His clients include tech companies and research institutions.
Jeffery C. Giering, PhD counsels pharmaceutical and biotechnology clients creating, acquiring, and managing intellectual property rights pertaining to genomics, sequencing, molecular diagnostics, therapeutic antibodies, stem cell therapies, cancer therapeutics, microbial genetics, and gene therapy.