UNEXPECTED RESULTS VERSUS UNEXPECTED MECHANISM
| July 28, 2023
In Re: John L Couvaras
Decided June 14, 2023
Before Lourie, Dyk and Stoll.
Summary
This precedential decision serves as a good lesson on what is necessary to overcome an obviousness rejection based on unexpected results. The applicant in this decision, however, failed to overcome the rejection due to arguing an unexpected mechanism instead of unexpected results.
Background
The applicant appeals a decision from the Patent Trial and Appeal Board (PTAB) affirming the Examiner’s rejection of the pending claims as obvious over prior art. Representative claim 11 recites:
11. A method of increasing prostacyclin release in systemic blood vessels of a human individual with essential hypertension to improve vasodilation, the method comprising the steps of:
providing a human individual expressing GABA-a receptors in systemic blood vessels due to essential hypertension;
providing a composition of a dosage of a GABA-a agonist and a dosage of an ARB combined into a deliverable form, the ARB being an Angiotensin II, type 1 receptor antagonist;
delivering the composition to the human individual’s circulatory system by co-administering the dosage of a GABA-a agonist and the dosage of the ARB to the human individual orally or via IV;
synergistically promoting increased release of prostacyclin by blockading angiotensin II in the human individual through the action of the dosage of the ARB to reduce GABA-a receptor inhibition due to angiotensin II presence during a period of time, and
activating the uninhibited GABA-a receptors through the action of the GABA-a agonist during the period of time; and
relaxing smooth muscle of the systemic blood vessels as a result of increased prostacyclin release. (emphasis added).
The applicant had conceded during prosecution that GABA-a agonists and ARBs had been known as essential hypertension treatments for many decades. The Examiner agreed and found that the claimed results (increased release of prostacyclin; activating the uninhibited GABA-a receptors; relaxing smooth muscle of the systemic blood vessels) were not patentable because they naturally flowed from the claimed administration of the known antihypertensive agents.
On appeal to the PTAB, the applicant asserted that the prostacyclin increase was unexpected and that objective indicia had overcome any existing prima facie case of obviousness. The PTAB affirmed the rejection, holding that the claimed result of an increased prostacyclin release was inherent, and that the objective indicia arguments did not overcome the rejection because no evidence existed to support a finding of objective indicium.
Discussion
The PTAB’s legal determination is reviewed de novo, and the factual findings are reviewed for substantial evidence.
Couvaras asserts that (1) the Board erred in affirming that motivation to combine the art applied by the Examiner, (2) that the claimed mechanism of action was unexpected in that the Board erred in discounting its patentable weight by deeming it inherent, and (3) that the Board erred in weighing objective indicia of nonobviousness.
1. Motivation to Combine
As explained by the Examiner and affirmed by the Board, “[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition which is to be used for the very same purpose.” Couvaras asserted that the Board’s reasoning was too generic. However, it is undisputed that the antihypertensive agents recited in the claims existed and were known to treat hypertension.
Couvaras also asserted that even if there had been a motivation to combine, such motivation would fail to identify a finite number of identified, predicted solutions. The CAFC dismissed this argument because (1) it was made in a footnote and thus waived, (2) there was no evidence presented regarding a “substantial number of hypertension treatment agent classes”, and (3) the Board’s conclusion was supported by substantial evidence.
Regarding a reasonable expectation of success, Couvaras did not present any arguments against the Examiner’s findings when the rejection was appealed.
2. Unexpected Mechanism of Action
Couvaras contends that because the increased prostacyclin release was unexpected, it cannot be dismissed as having no patentable weight due to inherency, citing Honeywell International Inc. v. Mexichem Amanco Holdings S.A.,865 F.3d 1348, 1355 (FED. Cir. 2017). This decision, however, held that unexpected properties may cause what may appear to be an obvious composition to be nonobvious, not that the unexpected mechanisms of action must be found to make the known use of known compounds nonobvious. As stated in the opinion:
We have previously held that “[n]ewly discovered results of known processes directed to the same purpose are not patentable because such results are inherent.” In re Montgomery, 677 F.3d 1375, 1381 (Fed. Cir. 2012) (citation omitted); see also In re Huai-Hung Kao, 639 F.3d 1057, 1070–71 (Fed. Cir. 2011) (holding that a “food effect” was obvious because the effect was an inherent property of the composition). While mechanisms of action may not always meet the most rigid standards for inherency, they are still simply results that naturally flow from the administration of a given compound or mixture of compounds. Reciting the mechanism for known compounds to yield a known result cannot overcome a prima facie case of obviousness, even if the nature of that mechanism is unexpected.”
3. Weighing objective indicia of nonobviousness
To establish unexpected results, Couvaras needed to show that the co-administration of a GABA-a agonist and an ARB provided an unexpected benefit, such as, e.g., better control of hypertension, less toxicity to patients, or the ability to use surprisingly low dosages. The CAFC agreed with the Board that no such benefits have been shown, and therefore no evidence of unexpected results exists.
Takeaways
- Evidence needs to be presented to rebut a prima facie rejection. It seems that the applicant was attempting to assert that the combined use of the 2 agents provided unexpected results (better than what would be expected) based on synergy. As set forth in MPEP 716.02, greater than expected results are evidence of nonobviousness.
MPEP 716.02(a)
Evidence of a greater than expected result may also be shown by demonstrating an effect which is greater than the sum of each of the effects taken separately (i.e., demonstrating “synergism”). Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989). However, a greater than additive effect is not necessarily sufficient to overcome a prima facie case of obviousness because such an effect can either be expected or unexpected. Applicants must further show that the results were greater than those which would have been expected from the prior art to an unobvious extent, and that the results are of a significant, practical advantage. Ex parte The NutraSweet Co., 19 USPQ2d 1586 (Bd. Pat. App. & Inter. 1991) (Evidence showing greater than additive sweetness resulting from the claimed mixture of saccharin and L-aspartyl-L-phenylalanine was not sufficient to outweigh the evidence of obviousness because the teachings of the prior art lead to a general expectation of greater than additive sweetening effects when using mixtures of synthetic sweeteners.).
It seems that no evidence was presented to support the applicant’s argument of synergy. In reviewing the prosecution history, there were two interviews with the primary Examiner, one of which also included the Supervisory Examiner (SPE)[1]. In the interview summary, the Examiners indicated that the claims were too broad in that there were no amounts recited, no dose regime and/or no specific agents recited. It seems that a successful outcome could have been possible if evidence had been presented which was commensurate in scope with the claims.
- Once an Examiner establishes a prima facie rejection, the burden shifts to the applicant to prove otherwise.
[1] It is never a good idea to call on the SPE to attend an interview with a Primary Examiner. This not only angers a Primary Examiner but also the SPE.
THE MORE YOU CLAIM, THE MORE YOU MUST ENABLE
| July 12, 2023
Amgen Inc. v. Sanofi
Decided: May 18, 2023
Supreme Court of the United States. Opinion by Justice Gorsuch
Summary:
Amgen owns patents covering antibodies that help reduce levels of low-density lipoprotein (LDL) cholesterol. Amgen sued Sanofi for infringement of its patents in district court. Sanofi raised the defense of invalidity for lack of enablement because while Amgen provided amino acid sequences for 26 antibodies, the claims cover potentially millions more undisclosed antibodies. The district court granted a motion for JMOL for invalidity due to lack of enablement, the CAFC affirmed, and the Supreme Court affirmed.
Details:
Amgen’s patents are to PCSK9 inhibitors. PCSK9 is a naturally occurring protein that binds to and degrades LDL receptors. PCSK9 causes problems due to degradation of LDL receptors because LDL receptors extract LDL cholesterol from the bloodstream. A method used to inhibit PCSK9 is to create antibodies that bind to a particular region of PCSK9 referred to as the “sweet spot” which is a sequence of 15 amino acids out of PCSK9’s 692 total amino acids. An antibody that binds to the sweet spot can prevent PCSK9 from binding to and degrading LDL receptors. Amgen developed a drug named REPATHA and Sanofi developed a drug named PRALUENT, both of which provide a distinct antibody with its own unique amino acid sequence. In 2011, Amgen and Sanofi received patents covering the antibody used in their respective drugs.
The patents at issue are U.S. Patent Nos. 8,829,165 and 8,859,741 issued in 2014 which relate back to Amgen’s 2011 patent. These patents are different from the 2011 patents in that they claim the entire genus of antibodies that (1) “bind to specific amino acid residues on PCSK9,” and (2) “block PCSK9 from binding to LDL receptors.” The relevant claims are provided:
Claims of the ‘165 patent:
1. An isolated monoclonal antibody, wherein, when bound to PCSK9, the monoclonal antibody binds to at least one of the following residues: S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, or S381 of SEQ ID NO:3, and wherein the monoclonal antibody blocks binding of PCSK9 to LDLR.
19. The isolated monoclonal antibody of claim 1 wherein the isolated monoclonal antibody binds to at least two of the following residues S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, or S381 of PCSK9 listed in SEQ ID NO:3.
29. A pharmaceutical composition comprising an isolated monoclonal antibody, wherein the isolated monoclonal antibody binds to at least two of the following residues S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, or S381 of PCSK9 listed in SEQ ID NO: 3 and blocks the binding of PCSK9 to LDLR by at least 80%.
Claims of the ‘741 patent:
1. An isolated monoclonal antibody that binds to PCSK9, wherein the isolated monoclonal antibody binds an epitope on PCSK9 comprising at least one of residues 237 or 238 of SEQ ID NO: 3, and wherein the monoclonal antibody blocks binding of PCSK9 to LDLR.
2. The isolated monoclonal antibody of claim 1, wherein the isolated monoclonal antibody is a neutralizing antibody.
7. The isolated monoclonal antibody of claim 2, wherein the epitope is a functional epitope.
In its application, Amgen identified the amino acid sequences of 26 antibodies that perform these two functions. Amgen provided two methods to make other antibodies that perform the described binding and blocking functions. Amgen refers to the first method as the “roadmap,” which provides instructions to:
(1) generate a range of antibodies in the lab; (2) test those antibodies to determine whether any bind to PCSK9; (3) test those antibodies that bind to PCSK9 to determine whether any bind to the sweet spot as described in the claims; and (4) test those antibodies that bind to the sweet spot as described in the claims to determine whether any block PCSK9 from binding to LDL receptors.
Amgen refers to the second method as “conservative substitution” which provides instructions to:
(1) start with an antibody known to perform the described functions; (2) replace select amino acids in the antibody with other amino acids known to have similar properties; and (3) test the resulting antibody to see if it also performs the described functions.
Amgen sued Sanofi for infringement of claims 19 and 29 of the ‘165 patent and claim 7 of the ‘741 patent. Sanofi raised the defense of invalidity because Amgen had not enabled a person skilled in the art to make and use all of the antibodies that perform the two functions Amgen described in the claims. Sanofi argued that Amgen’s claims cover potentially millions more undisclosed antibodies that perform the same two functions than the 26 antibodies identified in the patent.
The court provided an explanation of the law and policy regarding the enablement requirement. 35 U.S.C. § 112 requires that a specification include “a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art … to make and use the same.” The court stated:
the law secures for the public its benefit of the patent bargain by ensuring that, upon the expiration of [the patent], the knowledge of the invention [i]nures to the people, who are thus enabled without restriction to practice it.
The court stated that “the specification must enable the full scope of the invention as defined by its claims.” Specifically, the court stated:
If a patent claims an entire class of processes, machines, manufactures, or compositions of matter, the patent’s specification must enable a person skilled in the art to make and use the entire class.
The court emphasized that the enablement requirement does not always require a description of how to make and use every single embodiment within a claimed class. A few examples may suffice if the specification also provides “some general quality … running through” the class. A specification may also not be inadequate just because it leaves a skilled artisan to engage in some measure of adaptation or testing, i.e., a specification may call for a reasonable amount of experimentation to make and use a patented invention. “What is reasonable in any case will depend on the nature of the invention and the underlying art.”
Regarding this case, the court stated that while the 26 exemplary antibodies provided by Amgen are enabled by the specification, the claims are much broader than the specific 26 antibodies. And even allowing for a reasonable degree of experimentation, Amgen has failed to enable the full scope of the claims.
The court stated that Amgen seeks to monopolize an entire class of things defined by their function and that this class includes a vast number of antibodies in addition to the 26 that Amgen has described by their amino acid sequences. “[T]he more a party claims, the broader the monopoly it demands, the more it must enable.”
Amgen argued that the claims are enabled because scientists can make and use every undisclosed but functional antibody if they simply follow Amgen’s “roadmap” or its proposal for “conservative substitution.” The court stated that these instructions amount to two research assignments and that they leave scientists “forced to engage in painstaking experimentation to see what works.” The court referred to Amgent’s two methods as “a hunting license.”
Comments
The key takeaway from this case is that the broader your claims are, the more your specification must enable. If it is difficult to show enablement for every embodiment claimed, then make sure your specification describes some general quality throughout the class or genus. A reasonable amount of experimentation is permissible for enablement, but reasonableness will depend on the nature of the invention and the underlying art.
