During the week of January 7, the Patent Trial and Appeal Board (“the Board”) issued four decisions in TC 1600, one denying institution of inter partes review (“IPR”) and three final written decisions.  Summaries of the decisions follow:

CSL Behring LLC, CSL Behring GMBH, and CSL Behring Recombinant Facility AG (“CSL”) v. Bioverativ Therapeutics Inc. (“Bioverativ”), IPR2018-01313 (Decision Denying Institution of IPR Entered January 9, 2019).

In its petition, CSL challenged claims 1-28 of U.S. Patent No. 9,623,091 (“the ’091 patent”), directed to methods of administering Factor IX using chimeric polypeptides comprising Factor IX and an FcRn binding partner to treat hemophilia B.

CSL challenged claims 1-28 of the ’091 patent as obvious over the combined teachings of: (1) Peters and Shapiro and/or (2) Metzner and/or U.S. Pat. Pub. No. 2008/0260755 (the ’755 publication) in view of Shapiro and Carlsson.  The challenged claims are directed methods of treating hemophilia B in humans by intravenously administering doses of 50 IU/kg to about 100 IU/kg of a chimeric Factor IX peptide.  Doses are administered about intervals of about 10 to about 14 days.  In particular, the chimeric Factor IX peptide comprises Factor IX and an FcRn binding partner, such as Fc or albumin.  Following administration of the chimeric Factor IX peptide, the human subject’s plasma Factor IX activity is maintained above 1 IU/dL.  IPR2018-01313, Paper 10 at 3-4.

Peters was relied upon by the examiner in support of an obviousness rejection during prosecution; however, the examiner later admitted that Peters was not prior art following Bioverativ’s arguments and 1.132 declaration in support of the same.  Id. at 10.  CSL argued that the examiner’s removal of Peters as prior art was improper at least because (1) the relevant inquiry is whether the Peters disclosure was attributable only to inventors of the ’091 patent, and (2) the “averments that coauthors were carrying out experiments under Peters’ direction and control are insufficient” in view of the authorship section of Peters, “which indicates that other coauthors designed research, and ‘paragraphs 4-5 of Peters’s declaration, which suggest that he took credit for directing and controlling all the work.’”  Id. at 10-11.

Analyzing CSL’s arguments regarding Peters, the Board turned to the Federal Circuit’s Katz decision which “determined that a reference by an inventor co-authored with non-inventors was not § 102(a) prior art on the basis that the co-authors contribution fails to rise to joint inventorship, and not on the basis that they made no contribution. Katz, 687 F.2d at 455–56 (‘the board . . . should have accepted that [the co-authors] were acting in the capacity indicated, that is, students working under the direction and supervision of appellant’).”  Id. at 11 (quoting In re Katz, 687 F.2d 450, 455 (C.C.P.A. 1982)).  The Board ultimately disagreed with CSL and determined that the record supports Bioverativ’s position that Peters was responsible for the content of the Peters reference, resulting in the reference not being prior art to the ’091 patent.

CSL further contended that the ’091 patent cannot properly claim priority to any of the provisional applications in its priority chain because they “do not satisfy the written description and enablement requirements for the ’091 patent claims.”  IPR2018-01313, Paper 10 at 13.  CSL’s arguments regarding written description and enablement largely focus on the Factor IX and FcRn binding partner disclosures in the provisional applications as including a large number of proteins having a wide variety of structural variations.  CSL pointed to data for only one molecule of this class in the provisional applications and alleged that the limited data was insufficient to meet both the written description and enablement standards for the claimed invention.  However, as Bioverativ pointed out in its response, CSL’s allegations are “based on an incomplete reading of the Priority Applications” and, thus, ignore disclosure relevant to the adequacy of the written description, such as the PCT applications, U.S. patents, and other references incorporated therein.  Id. at 15.  The Board agreed with Bioverativ and determined that CSL failed to meet their burden to show that the ’091 patent was not entitled to its priority date, which eliminated Peters as 102(b) prior art, and, accordingly, found CSL’s obviousness grounds based on Peters to be unpersuasive.

With respect to CSL’s allegation that claims 1-28 are unpatentable for being obvious over Metzner and/or the ’755 publication in view of Shapiro and Carlsson, the Board disagreed.  According to the Board, CSL failed to establish (1) that once weekly doses taught by Shapiro maintained a subject’s Factor IX activity above 1 IU/dL, (2) that “inconsistencies in Metzner and the ’755 publication as to half-life data in animal models, and the application of that half-life data to dosing and dosing intervals in human patients” are not immaterial, and (3) why “one skilled in the art would not have found the half-life data for FIX-deficient mice to undercut an expectation of half-life extension in human patients suffering from hemophilia B.”  IPR2018-01313, Paper 10 at 25-26.

As such, the Board concluded that CSL failed to demonstrate by a preponderance of the evidence that claims 1-28 the ’091 patent would have been obvious.

 

Nuevolution A/S (“Nuevolution”) v. Chemgene Holdings APS (“Chemgene”)

In all three of the IPRs summarized below, the Board instituted trial only on certain grounds.  Nevertheless, after the Supreme Court’s decision in SAS Institute, Inc. v. Iancu, 138 S. Ct. 1348 (2018), the Board modified the institution decision in each of the following IPRs to include the remaining grounds in the trial proceedings.

As an initial matter, the Board construed one claim term, found in all independent claims of the challenged patents, consistently across all three IPR proceedings.  All three decisions turn on the Board’s interpretation of this claim term, which is, “one or more reaction wells . . . each of said reaction wells.”  According to the Board, “‘one or more reaction wells . . . each of said reaction wells’ means that the synthesis of any particular bi-functional molecule . . . is conducted within the same reaction well because ‘said’ indicates that the reaction wells . . . are the same.”  See, e.g., IPR2017-01598, Paper 47 (Final Written Decision) at 21.  The Board reiterated this point when explaining that “a particular bi-functional molecule is synthesized by a linker becoming attached to a respective molecule fragment and oligonucleotide identifier is, for example, a tube or a nanocompartment in that tube, it must be the same reaction well — the same physical containment and localized space.”  Id.

In its petition, Nuevolution challenged claims 1, 2, 4, 5, 7-9, 16, 18-23, 27-30, 32, 33, 35, 36, 38-41, 42, 43, 45, and 46 of U.S. Patent No. 8,168,381 (“the ’381 patent”), which is directed to synthesis of encoded molecule fragments using mix and split techniques as well as template directed synthesis.

Independent claim 1 is representative and recites:

1. A method for synthesizing an encoded molecule comprising the steps of:

a) Adding a linker molecule L to one or more reaction wells;
b) Adding a molecule fragment to each of said reaction wells;
c) Adding an oligonucleotide identifier to each of said reaction wells;
d) Subjecting said wells to conditions sufficient to allow said molecule fragments and said oligonucleotide identifiers to become attached to said linker molecule, or conditions sufficient for said molecule fragments to bind to other molecule fragments and sufficient for said oligonucleotide identifiers to bind to other oligonucleotide identifiers, so as to form bi-functional molecules consisting of an encoded molecule and an oligonucleotide;
e) Combining the contents of said one or more reaction wells, to produce an admixture of said bi-functional molecules;
f) Optionally, distributing the combined product to one or more new reaction wells;
g) Optionally, repeating steps b) to f) one or more times; and
h) Contacting the resulting bifunctional molecule(s) of step e) or g) with one or more templates each capable of hybridizing to at least one of the oligonucleotide identifiers added in step c);
wherein
the linker molecule L contains at least one reactive group capable of reacting with a reactive group in the molecule fragment and at least one reactive group capable of reacting with a reactive group in the oligonucleotide;
the molecule fragments each contain at least one reactive group capable of reacting with a reactive group in the linker molecule L or a reactive group in another molecule fragment, and the reactive groups of each molecule fragment may be the same or different;
the oligonucleotide identifiers each contain at least one reactive group capable of reacting with a reactive group in the linker L or a reactive group in another oligonucleotide identifier, and the reactive groups of each oligonucleotide identifier may be the same or different;
the region of the oligonucleotide identifier added to each well in step c) which hybridizes to said template identifies the molecule fragment added to the same well in step b);
the steps a) to d) may be performed in any order;
the steps b) to d) in step g) may also be performed in any order;
the number of wells in steps a) and f) may be the same or different; and
the oligonucleotide template optionally is associated with a reactive group.

IPR2017-01598, Paper 47 (Final Written Decision) at 11-12.

The claims were challenged on eleven grounds of anticipation and/or obviousness in view of one or more of Gouliaev ’627, Gouliaev ’994, Pedersen, Franch ’929, Liu, and Freskgård.  The Board instituted trial on three of the eleven grounds and its Final Written Decision discusses the same in detail.  While the remaining eight grounds were added following the Supreme Court’s decision in SAS, the Board’s decision turned on the institution grounds.

First, the Board addressed Nuevolution’s asserted anticipation ground based on Freskgård and pointed out that “a key dispute here is whether the asserted prior art discloses that particular bi-functional (carrier) molecules are synthesized according to the claimed steps in the same reaction well.”  Id. at 32.  While Nuevolution argued that Freskgård disclosed that the claimed steps take place in the same reaction well (in particular—at Figure 12 which shows a 96-well microtiter plate where the disclosed process occurs in each well), Chemgene argued that Freskgård disclosed the use of different reaction wells for preparation of bi-functional carriers.  The Board agreed with Nuevolution’s additional arguments regarding the claimed linker molecule, finding that “‘linker molecule L’ as claimed encompasses, at minimum, Freskgård’s nascent bi-functional complexes, such as shown in Freskgård’s Figure 13, to which particular molecule fragments and codon oligos are reacted and attached in individual wells of a microtiter plate.”  Id. at 44.  Unfortunately for Nuevolution, the Board ultimately agreed with Chemgene’s arguments that even if Freskgård discloses all features of the claimed method, Nuevolution relied upon individual steps from protocols of unrelated embodiments within Freskgård in violation of Net MoneyIN.   

Second, in advancing its position that the claims are obvious in view of Freskgård, Nuevolution argued that each and every element of the claims is disclosed by Freskgård and it would be advantageous to combine the protocols of each of Freskgård’s embodiments (Modes 1 and 2) because Mode 2 provides versatile reactions, and Mode 1 provides high local concentrations of reactants.  Id. at 50.  The Board agreed because, while picking and choosing from embodiments may not be proper for an anticipation analysis, it may be for an obviousness rejection where, as here, there are “several evidence-backed reasons that we [the Board] find explain why the skilled person would have predictably and advantageously combined Mode 2 and Mode 1 techniques to arrive at the subject matter of the challenged claims.”  Id. at 53.  Chemgene’s arguments to the contrary did not persuade the Board otherwise at least because the “argument that there is no sufficient motivation or reasonable expectation of success in combining those techniques … is inconsistent with at least Freskgård’s express teachings and substantial expert testimony in this case.”  Id.  Accordingly, while the Board concluded that Nuevolution failed to demonstrate, by a preponderance of the evidence, that claims 1, 4, 5, 7–9, 16, 19–22, 27–30, 32, 33, 35, 36, and 38–41 of the ’381 patent are anticipated by Freskgård, the Board determined that Nuevolution had successfully demonstrated that these claims are obvious in view of Freskgård.

Third, the Board agreed with Nuevolution regarding its allegation that the claims having features of template-directed synthesis methods are obvious in view of Freskgård and Pederson.  The Board explained that, “[w]hen combined with bi-functional molecules synthesized according to Freskgård’s Mode 2 (split-and-mix) technique,” they find that “the skilled artisan would have had reason to combine the split-and-mix and template-directed techniques to obtain the known advantages of each of those techniques.”  IPR2017-01598, Paper 47 at 63.  Since “the skilled artisan would have had a reasonable expectation of success in carrying out the method claimed,” at least for the same reasons discussed with respect to the anticipation and obviousness grounds based on Freskgård alone, Nuevolution demonstrated by a preponderance of the evidence that claims 1, 2, 4, 5, 7–9, 16, 18–22, 27–30, 32, 33, 35, 36, 38–41, and 46 are unpatentable for being obvious over Freskgård and Pedersen.  Id. at 63-64.

In sum, the Board found Nuevolution had demonstrated by a preponderance of the evidence that claims 1, 2, 4, 5, 7-9, 16, 18-23, 27-30, 32, 33, 35, 36, 38-41, 42, 43, 45, and 46 were unpatentable.

In its petition, Nuevolution challenged claims 1, 3, 5, 6, 10-15, 17, 23-26, 31, 34, 37, 44, and 45 of the ’381 patent.  Representative claim 1 is provided above.  The claims were challenged on seven grounds of anticipation and/or obviousness in view of one or more of Pedersen, Franch ’929, Franch ’427, and Freskgård.  The Board instituted trial on five of the seven grounds and its Final Written Decision discusses the same in detail.  While the remaining two grounds were added following the Supreme Court’s decision in SAS, the Board’s decision turned on the institution grounds.

Similar to its reasoning on anticipation and obviousness grounds based on Freskgård in IPR217-01598, the Board found Nuevolution had demonstrated by a preponderance of the evidence that claims 1, 3, 5, 6, 10-15, 17, 23-26, 31, 34, 37, 44, and 45 were unpatentable.

In its petition, Nuevolution challenged claim 1 of U.S. Patent No. 8,951,728 (“the ’728 patent”), which is directed to methods for synthesizing encoded molecules.

Independent claim 1 is representative and recites:

1. A method for synthesizing an encoded molecule comprising the steps of:

a) Adding a linker molecule L to one or more reaction wells;
b) Adding a molecule fragment to each of said reaction wells;
c) Adding an oligonucleotide identifier to each of said reaction wells;
d) Subjecting said wells to:
conditions sufficient to allow said molecule fragments and said oligonucleotide identifiers to become attached to said linker molecule, or
conditions sufficient for said molecule fragments to bind to other molecule fragments and sufficient for said oligonucleotide identifiers to bind to other oligonucleotide identifiers;
e) Combining the contents of said one or more reaction wells;
wherein at least one reactive group of the linker molecule L reacts with a reactive group in the molecule fragment, or with a reactive group in the oligonucleotide;
wherein at least one reactive group of the molecule fragments reacts with a reactive group in the linker molecule L, or with a reactive group in another molecule fragment,
wherein at least one reactive group of the oligonucleotide identifiers reacts with a reactive group in the linker L, or with a reactive group in another oligonucleotide identifier; and
wherein the region of the oligonucleotide identifier added to each well in step c), which hybridizes to said template identifies the molecule fragment added to the same well in step b).

IPR2017-01603, Paper 45 (Final Written Decision) at 10-11.

The claims were challenged on fourteen grounds of anticipation and/or obviousness in view of one or more of Gouliaev ’627, Gouliaev ’994, Pedersen, Franch ’929, Franch ’427, and Freskgård.  Id. at 11-12.  The Board instituted trial on four of these grounds and its Final Written Decision discusses the same in detail.  While the remaining ten grounds were added following the Supreme Court’s decision in SAS, the Board’s decision turned on the institution grounds

Similar to its rationale discussed above with respect to Nuevolution’s anticipation and obviousness grounds relying on Freskgård in IPR2017-01598, the Board found Nuevolution had demonstrated by a preponderance of the evidence that claim 1 is unpatentable.