By Kevin E. Noonan –

On August 25^th, the Patent Trial and Appeal Board (PTAB) of the U.S. Patent and Trademark Office designated as Informative its decision in Ex parte Chowdhury, directed toward what constituted improper Markush groupings (see Ex parte Markush, 1925 Dec. Comm’r Pat. 126, 127 (1924) and In re Harnisch, 631 F.2d 716, 719-20 (CCPA 1980), reversing the final rejection of the Examiner.

The decision arose over examination of claims to methods for treating radiation-induced damage in a human as recited in this (and other) claims:

60.  A method of treating radiation-induced damage in a human subject in need thereof, the method comprising:

(a)  determining at a first time point a first level of one or more miRNAs in a first serum sample obtained from the human subject, wherein the one or more miRNAs is selected from the group consisting of miR-130a-3p, miR-150-Sp, miR-142-Sp, miR-706, miR-342-3p, miR-136-Sp, miR-17-3p, miR-126-3p, miR-322-3p, miR-34b-3p, miR-187-3p, miR-194-Sp, miR-27a-3p, miR-30a-3p, and miR-30c-5p;

(b)  after the first time point and before a second time point, administering a first treatment for reducing radiation induced damage to the human subject, wherein the first treatment for reducing radiation-induced damage is selected from the group consisting of: a cytokine, potassium iodide, Prussian blue, diethylenetriamine pentaacetic acid, bone marrow transplantation, blood transfusion, and surgery to remove damaged tissues;

(c)  determining a second level of the one or more miRNAs of step (a) in a second serum sample obtained from the human subject at the second time point; and

(d) (i) determining that the first treatment administered in step (b) was effective and administering one or more additional doses of the first treatment for reducing radiation-induced damage to the human subject; or

(d) (ii) determining that the first treatment administered in step (b) was not effective and administering a second treatment for reducing radiation-induced damage to the human subject, wherein the first treatment for reducing radiation induced damage is not the same as the second treatment for reducing radiation-induced damage;

wherein one or more of:

(i)  an elevation in the second level of one or more miRNAs selected from the group consisting ofmiR-136-Sp, miR-322-3p, miR-142-Sp, miR-706, miR-150-Sp, miR-342-3p, miR-17-3p, miR-187-3p, miR-194-Sp, and miR-27a-3p, and

(ii)  a decrease in the second level of one or more miRNAs selected from the group consisting ofmiR-130a-3p, miR-126-3p, miR-34b-3p, miR-30a-3p, and miR-30c-Sp, as compared to the first level(s) of one or more miRNAs selected from the group consisting of miR-136-Sp, miR-322-3p, miR-142-Sp, miR-706, miR-150-Sp, miR-342-3p, miR-17-3p, miR-187-3p, miR-194-Sp, miR-27a-3p, miR-130a-3p, miR- 126-3p, miR-34b-3p, miR-30a-3p, and miR-30c-5p, indicates that the treatment for reducing radiation-induced damage administered to the human subject was effective.

The Examiner rejected this claim on the basis that it was an incorrect Markush group.  The basis for this allegation was that the recited lists of miRNAs did not “share [sufficient] structural similarity” amongst themselves, which the Examiner identified as “that all of the miRNAs comprise nucleotides.”  Also, “they do not belong to a chemical or art-recognized class,” and “there is no expectation from the knowledge in the prior art that the miRNAs behave in the same manner and can be substituted for one another with the same intended result achieved.”  What the Examiner did recognize as being in common was “the property of being correlated with radiation exposure” (i.e., a similarity in function) but even then “they do not share a substantial structural similarity essential to this activity.”  Thus, the Examiner concluded “the recited miRNAs are not members of the same recognized physical or chemical class or the same art-recognized class” and did not satisfy the requirements set forth in  M.P.E.P. § 706.07 (which is now set forth in M.P.E.P. § 2117).

The Applicant made the distinction that, unlike the requirements for Markush claims recited in claims to a single compound, when recited in claims for a process or combination propriety of collection in a Markush group is satisfied when the recited components “possess at least one property in common which is mainly responsible for their function in the claimed relationship,” i.e., “they all possess this [same] property.”  Accordingly, because these claims recite “methods of treating that use a cellular state or miRNA signature that is present after exposure to radiation” their collection into a Markush group in the rejected claims were proper.  Also, they are used in these claims as “markers” for the shared functional activity and thus “substitutable for one another and . . . are structurally similar enough to be classified as a unified class.”

The Board was persuaded by this argument, relying on In re Harnisch, 631 F.2d 716 (CCPA 1980) and In re Jones, 162 F.2d 479 (CCPA 1947), for the capacity of recited common function being enough as comprising a common “unity of invention” under Jones for having a common function.  Citing Multilayer Stretch Cling Film Holdings, Inc. v. Berry Plastics Corp., 831 F.3d 1350, 1357 (Fed. Cir. 2016) (“It is generally understood that . . . the members of the Markush group . . . are alternatively usable for the purposes of the invention. . . .“)(emphasis in PTAB opinion), the Board set forth the propriety of inclusion into a Markush group to be “if a recited Markush group lists a set of things that the inventor describes as a subgenus, and those things are described in the specification as useful for the function of the invention because of their similarities,” in accordance with the provisions of M.P.E.P. § 2117.II.A.  Importantly, the opinion also asserts that “a Markush group’s species may be structurally divergent . . . but if they would be expected to perform the same function in the context of the invention, they are properly grouped.”

The Board discerns that the Examiner had acknowledged “some structural and functional similarity amongst the recited group of miRNAs, in the context of the invention.”  A distinction here is that the recited miRNAs in the Markush group need not have to “function as miRNAs,” provided that “the claimed miRNA species as representative of a patient’s exposure to radiation, as they are quantifiable and can be observed to either increase or decrease in quantity as a patient’s reaction to such exposure” (which is a reasonable definition for many biomarkers).  This functionality (“need[ing] only be quantifiable”) is common amongst the members of the species recited in the Markush group.  This is the case even if the miRNA’s are not the same (“the diversity of miRNA species may be structurally different”).

The Board synopsizes the standard for proper inclusion in a Markush group to be “if the members of a group share a single structural similarity [which here is apparently being miRNAs] and a common use” and as claimed in this case to be “whether the claimed miRNAs are produced in response to radiation exposure, and at what level they are produced” because the individual miRNA species are “interchangeable” for that purpose.

This decision does suggest a few distinctions that can be made more generally, particularly in the context of the decades-long changes in what is required for satisfaction of enablement and written description (which is not generally changed or limited in response).  It raises the question of what the members of a Markush group are used for, and whether that might have a disparate impact on outcomes.   For example, in Amgen v. Sanofi, 26 distinct antibodies disclosed by Amgen and immunologically specific for certain amino acid sequences in PCSK9 were the basis for having a cholesterol-lowering effect.  The Supreme Court found claims to the broader group, based on their function with regard to binding affinity to the particular amino acids, to be invalid for lack of enablement, because identifying the much larger number of such antibodies having this binding affinity function amounted to undue experimentation.  This outcome was consistent with the aforementioned tightening of enablement standards.  At least with regard to the possibility of expanding this group, provided that a Markush group is proper due to common use, then the structural similarity resulting from common complementarity-determining regions (CDRs) might provide a way to nudge the needle away from a “what you see is only what you get” standard which is arguably what exists for antibody claims under current law.  It might at a minimum be worth a try for some claims in some applications for some antibodies, specifically ones that as in Chowdhary are directed to combinations and methods rather than the antibody compounds per se.

Ex parte Chowdhury (PTAB 2026)
Panel:  Administrative Patent Judges Katz, Flax, and Hardman
Decision on Appeal by Administrative Patent Judge Flax