Publications – Oblon, McClelland, Maier & Neustadt, L.L.P.

Are you actually a Joint Inventor?

22 May 2023 00:00:00 -0800

The Court of Appeals for the Federal Circuit (CAFC), on May 2, 2023, reversed the Delaware District Court’s decision in HIP, Inc. v. Hormel Foods Corp., that David Howard of Unitherm should be added as a joint inventor on US 9,980,498 (herein, the ‘498 patent), a patent owned by Hormel and directed to methods of precooking bacon and meat pieces. The decision on appeal considered whether Howard contributed to the conception of the invention and whether the determination of his joint inventorship should be upheld.

In 2005, Hormel and Van Doorn of Unitherm entered into a joint agreement to develop an oven to be used in a two-step cooking process. During this agreement, two different ovens were utilized for testing. One oven was an infrared oven and the other was a more conventional spiral oven. Howard claimed during these initial meetings that he disclosed the infrared preheating concept at issue on appeal. In 2008, Hormel conducted additional testing using Unitherm’s mini spiral test oven at Unitherm’s research facility upon leasing the oven from Unitherm. Subsequent testing at Hormel’s own facility resulted in a two-step cooking process being developed. The first step involved preheating the bacon and the second step involved cooking the meat in a superheated steam oven. Upon developing the process, Hormel filed a non-provisional patent on the two-step cooking process in August 2011. The application issued in May 2018 as the ‘498 patent. The ‘498 patent named four inventors, who all assigned their interests in the patent to Hormel.

In 2021, HIP sued Hormel in the District Court of Delaware claiming that Howard was either the sole inventor or a joint inventor of the ‘498 patent based on various claims. At the bench trial, the district court determined Howard was not the sole inventor, but that he was a joint inventor based solely on his alleged contribution of the infrared preheating in claim 5. The court stated that the infrared preheating concept in claim 5 was significant based on the differences between independent claim 1 and independent claim 5. The differences between claim 1 and claim 5 are shown below:

Claim 1: A method of making precooked bacon pieces using a hybrid cooking system, comprising:
Preheating bacon pieces with a microwave oven to a temperature of 140° F. to 210° F… .

Claim 5: A method of making precooked bacon pieces using a hybrid cooking system, comprising:
Preheating bacon pieces in a first cooking compartment using a preheated method selected from the group consisting of a microwave oven, an infrared oven, and hot air to a temperature of at least 140° F… .

The district court determined that Howard was a joint inventor based on his contribution of the concept of preheating with an infrared oven identified in claim 5. This was corroborated by testimony from Van Doorn, pork loin testing date, and by three of the Hormel inventors stating they had not conceived of this particular element. The district court ordered the USPTO to add David Howard as a joint inventor on the ‘498 patent and to issue a Certificate of Correction accordingly.

On appeal to the CAFC, Hormel raised two issues. Firstly, Hormel argued that the district court erred in determining Howard was a joint inventor because the alleged contribution of preheating with an infrared oven was well known and part of the state of the art. Hormel asserted that its claim to alternatively using an infrared oven was not significant when measured against the scope of the full invention. Secondly, Hormel contended that the court erred in holding that HIP met its burden of establishing by clear and convincing evidence that Howard is a joint inventor because Howard’s testimony was insufficiently corroborated.

The CAFC identified that inventorship is a question of law, reviewed without deference to the district court, and noted that the burden of proving that an individual should be added as an inventor to an issued patent is a heavy one, because the patent that issued creates a presumption that the named inventors are the true and only inventors, citing to Pannu v. Iolab Corp, 155 F.3d 1344, 1349 (Fed. Cir. 1998) and Garrett Corp. v. United States, 422 F.2d 874, 880 (Ct. Cl. 1970). As a result, an allegedly excluded inventor must prove a claim to joint inventorship by clear and convincing evidence. e.g., Hess v. Advanced Cardiovascular Sys., Inc., 106 F.3d 976, 980 (Fed. Cir. 1997). Inventorship in the US has always been conception, but a test for sufficiency of the contribution to qualify in joint inventorshipcontests to that conception was set forth in Pannu, which the CAFC applied. Pannu, 155 F.3d at 1351. The Pannu factors require that a joint inventor: (1) contributed in some significant manner to the conception of the invention; (2) made a contribution to the claimed invention that is not insignificant in quality, when that contribution is measured against the dimension of the full invention; and (3) did more than merely explain to the real inventors well-known concepts and/or the current state of the art.

Hormel argued that Howard (from HIP) did not satisfy factor (3) of the Pannu test, based on a prior printed publication, i.e., US 2004/0131738 A1 (Holm), that identified preheating pieces of meat with an infrared oven. Hormel argued that the district court erred by not taking into account this prior disclosure and only looking at the claim language to determine whether preheating with an infrared oven reflected the state of the art. Hormel additionally argued that Howard did not satisfy factor (2) of the Pannu test, stating that the district court’s finding that Howard was not the sole inventor clearly identifies that he did not contribute to the overall conception of the claimed method, but only suggested using a piece of equipment. Hormel noted that the specification of the ‘498 patent mentions “infrared ovens” only once, compared to “microwave ovens” mentioned multiple times, including the figures. Finally, Hormel argued that the infrared oven recitation in claim 5 does not make the ‘498 patent patentable, and therefore the recitation should not make the infrared oven contribution significant.

The CAFC agreed with Hormel’s argument regarding the second Pannu factor, thus not addressing the other arguments. The court held that Howard’s alleged contribution of pre-heating meat pieces using an infrared oven was “insignificant in quality” to the claimed invention given the frequency of microwave ovens in the description and drawings of the ‘498 patent. The CAFC noted the single usage of “infrared oven” in the specification, as well as the single recitation in claim 5, determining that the use of a microwave was much more significant in determining the dimension of the full invention. The majority of the specification, the examples and corresponding figures for the preheating step employed a microwave oven, and not an infrared oven, according to the CAFC. The HIP Court summarized that “the specification, claims, and figures all illustrate that Howard’s alleged contribution of preheating the bacon or meat pieces with an infrared oven is ‘insignificant in quality’ when ‘measured against the dimension of the full invention,’ … which squarely focuses on a preheating step using a microwave oven.” The CAFC did not need to visit the other Pannu factors, as a failure to meet any one factor is dispositive on the question of inventorship. Thus, the CAFC did not address HIP’s argument that Holm, describing a technique never described in a marketing or sales brochure or in a textbook, was too obscure to qualify as a well-known concept and/or the current state of the art, relevant to factor (3) in the Pannu test.

Application

The decision in HIP, Inc. v. Hormel Foods Corp affirmed that the Pannu test is controlling law in determining qualification for joint inventorship. The CAFC found it persuasive that the ubiquity in the written description of an undisputedly prior art technique, i.e., microwave heating, suffices to discount the claiming of a lesser known technique, i.e., infrared heating, likely because neither heating technique was itself necessary to the inventive concept of a first heating step to form a fat or grease barrier layer around the pre-cooked meat to reduce condensation and flavor dilution. Ensuring correct inventorship for applications in joint inventorship situations may require considering the frequency in the description and drawings of an alternative claim element, particularly regarding a use of alternative prior art elements for achieving a result important to conception. In considering the second factor of the Pannu test and the issue of frequency, Howard's technique was “recited only once in a single claim ..., in a Markush group reciting a microwave oven, an infrared oven, and hot air,” whereas the other (two) independent claims “only recite[d] … preheating … with a microwave oven and d[id] not recite preheating with an infrared oven.” The CAFC will weigh the "significance," in the Pannu test, of an optional technique to the claimed invention substantially based on the frequency in the description and drawings, as well as recitation in the claims.

It's Time to Change How Antibodies Are Claimed in Patent Strategy

22 May 2023 00:00:00 -0800

Daniel Pereira, PhD, Managing Partner of Oblon, analyzes the impact of the US Supreme Court's ruling in Amgen v. Sanofi, in an article entitled, "It's Time to Change How Antibodies Are Claimed in Patent Strategy," as published in the May 22, 2023 issue of Bloomberg Law.

PTAB Denies Motion to Amend Claims After Determining the Term "High Pressure" is Indefinite

16 May 2023 00:00:00 -0800

The Patent Trial and Appeals Board denied U.S. Well Services, LLC’s (the Patent Owner) Motion to Amend the claims of U.S. Patent No. 10,254,732 B2 (the ‘732 Patent) during inter partes review after determining that the term “high pressure” as used in the amended claims was indefinite under 32 U.S.C. §112(b). See Haliburton Energy Services, Inc., v. U.S. Well Services, LLC, IPR2022-00074, Final Written Decision Granting in Part and Denying in Part Patent Owner’s Revised Non-Contingent Motion to Amend at 3. The Patent Owner moved to cancel claims 1-13 and substitute the canceled clams with claims 14-26. As a preliminary matter, the Board found that the Patent Owner met the statutory threshold for amending the claims by ruling that the recited camera data bypass feature did not constitute “new matter.” Id. at 21.

Claim 14 recites a system for use with a fracturing operation, comprising “a plurality of…pumps fluidly connected to a well…and configured to pump fluid into the well at high pressure so that the fluid passes from the well into the formation, and fractures the formation” (emphasis added). Id. at 7. Haliburton challenged claim 14 arguing that the term “high pressure” was an indefinite term of degree because the “baseline” of the term was unclear in the art of fracking. Id. at 26. The Board reiterated that under Interval Licensing, terms of degree are considered definite when the context of the invention provides enough certainty to a person of ordinary skill in the art. The Board also pointed to Liberty Ammunition, Inc. when stating that terms of degree are considered indefinite when the term’s “baseline” is unclear.

The Board ultimately concluded that the ‘732 Patent did not provide any guidance for what the patent meant by “high pressure.” Decision at 27. The Board found that the ‘732 Patent did not disclose a minimum pressure, nor did the ‘732 Patent describe how to measure pressure to determine if “high pressure” was being employed. The Board also noted that the prosecution history did not address the meaning of “high pressure.”

The Patent Owner was forced to rely on its Expert Witnesses, who gave conflicting answers when proffering pressure ranges that might meet the definition of “high pressure” as used in claim 14. The Patent Owner’s first expert, Mr. William Marscher, testified that a person of ordinary skill in the art would estimate “high pressure” as between 5,000 and 15,000 psi. Mr. Marscher also indicated that what was considered “high pressure” would also depend on the field, pointing out that in the waterjet cutting industry “high pressure” ranged from 20,000 to 40,000 psi. But Mr. Marscher concluded his statement that in the fracking industry, “high pressure” would range from 5,000 to 15,000 psi. Id. at 28.

The Patent Owner’s second expert, Mr. Robert Schaff, testified that a person of ordinary skill in the art of fracking would consider “high pressure” to range from 8,000 to 12,000 psi. Id. at 29. Mr. Schaaf refuted Mr. Marscher’s testimony, saying that a person of ordinary skill in the art of fracking would not consider 5,000-15,000 psi to be “high pressure.” Id. Mr. Schaaf also explained that the pressure needed to fracture the formation often depended on the formation itself and that certain fracking jobs cold be done as “pressures that are not high pressure.” Id.

Faced with no information in the ‘732 Patent itself that clarified what “high pressure” meant, and the conflicting ranges offered by the Patent Owner’s own experts, the Board agreed with the Petitioner’s Expert, Dr. Robert A. Durham, who testified that there generally was no consensus as to what ranges qualified as “high pressure.” Id. at 30.

The Board’s ruling should serve as a reminder that if a term of degree is used in the claims, the specification needs to provide a baseline definition for that term of degree to avoid indefiniteness issues.

PTAB Reverses Obviousness Rejection and Affirms Double-Patenting Rejection with Terminal Disclaimer

04 May 2023 00:00:00 -0800

Read Grace Kim's article entitled "PTAB Reverses Obviousness Rejection and Affirms Double-Patenting Rejection with Terminal Disclaimer", as published in the January/February 2023 edition of IP Litigator. A subscription can be purchased here. The article is available at the link below.

Amgen Supreme Court Arguments Aren't Just About Biology

24 Mar 2023 00:00:00 -0800

Sameer Gokhale is quoted in the Law360 article “Amgen Supreme Court Arguments Aren’t Just About Biology.”

Federal Circuit protects infringement demand letters as free speech

17 Mar 2023 00:00:00 -0800

Read Frank West’s article entitled “Federal Circuit protects infringement demand letters as free speech)”, as published in the March 17, 2023 edition of IAM. The First Amendment of the U.S. Constitution protects free speech in the context of licensing and other demand letters unless made in bad faith – a high standard that is difficult to meet under federal law. Defendants may have better success using state law abusive patent assertions acts which may place greater disclosure requirements for demand letters and broader definitions of what may constitute bad faith than federal law. Read more here.

Aso available at the link below.

Risk Evaluation and Mitigation Strategy Patent Not Listable in Orange Book

06 Mar 2023 00:00:00 -0800

The Federal Circuit on February 24^th affirmed the Delaware District order in Jazz Pharm., Inc. v. Avadel CNS Pharm., LLC., 2023-1186, that Jazz delist from the Orange Book its Patent 8,731,963 directed to a REMS to control access to its drug Xyrem, also known as gamma hydroxyl butyrate (GHB) which was misused to facilitate rape, the “date rape” drug.” The decision considered whether to list a drug in the Orange Book was proper. Patents may be listed in the Orange Book if it either claims the drug or methods of using the drug. 21 U.S.C. § 355(b)(FDCA) and 21 C.F.R. § 314.53(b)(1). Jazz contended that patent law did not provide the correct framework determining whether a patent should be listed in the Orange Book. Both the statute and rule look to the patent claims to determine if a patent claims either the drug or a method of using the drug. Here the issue was whether the ‘963 claims were directed to a method of using Xyrem.

The claims are:

1. A computer-implemented system for treatment of a narcoleptic patient with a prescription drug that has a potential for misuse, abuse or diversion, comprising:

one or more computer memories for storing a single computer database having a database schema that contains and inter- relates prescription fields, patient fields, and prescriber fields;

* * *

a data processor configured to:

* * *

said identifying that the narcoleptic patient is a cash payer by said second database query being an indicator of a potential misuse, abuse or diversion by the narcoleptic patient and being used to notify the physician that is interrelated with the narcoleptic patient through the schema of the single computer database.

6. The system of claim 1 wherein the prescription drug comprises gamma hydroxyl butyrate (GHB).

The district court had performed a claim construction deciding that the ‘963 patent was not a method of use patent under the FDCA which requires the patent “claims a method of using [the] drug for which approval is sought or has been granted in the application.” Jazz argued that the district court erred in not treating the claims as method claims which relate a REMS-based procedure. The Federal Circuit agreed with the district court that the claims are directed to a “system” and not a method. Like the district court the Federal Circuit noted the claims recite an “assemblage of components.” Jazz did not point to anything in the patent or the prosecution history which contradicts this conclusion.

The Court then turned to Jazz’ second point that 21 C.F.R. § 314.53(b)(1) which describes listing patents that “claim conditions of use,” informs the analysis of whether a patent claims “an approved method of using the drug” under § 355. Jazz argued this allowed for a broader definition of “method” than permitted under patent law. Jazz also points to subsections of 21 U.S.C. § 355 that use the phrase “conditions of use,” to establish that this term is inclusive of all patents claiming elements of an approved REMS. However, the conditions of use described in the rule describe conditions of use evaluated for efficacy, implicating “relevant science,” “clinical investigations,” and “establishing effectiveness” and determining whether a “new drug can be expected to have the same therapeutic effect as the listed drug when administered” according to the approved “conditions of use prescribed, recommended, or suggested in the labeling.” The Court did not consider these provisions to expand the meaning of “method of using the drug” which must take its meaning from patent law.

Jazz’ final argument was that to delist a patent does not permit delisting a patent which falls into a category neither requiring nor forbidden to be listed. Jazz argued that since it was permissive in 2014 to list the patent, § 355(c)(3)(D)(ii)(I) does not provide one with the power to request a delisting. The Federal Circuit affirmed the district court’s analysis that the provision does not require the listing to have violated law but may request an order requiring the patent holder to correct or delete listings for patents that do not claim the drug or a method of using the drug. As the ’963 patent claims neither and has been asserted in a patent infringement action against Avadel, §355(c)(3)(D)(ii)(I) provides Avadel with a delisting remedy.

The key is to remember that the patent claims should be directed to a method of using the drug, here they were to a system for using the drug. A better approach would have been to draft the claims to a method of using the drug using the claimed system. Here the claims could have been drawn to a patient selection scheme which may have avoided the Court’s criticisms.

Federal Circuit Reiterates: Isolated Natural Products Alone Are Not Patent Eligible Without A Markedly Different Characteristic

03 Mar 2023 00:00:00 -0800

co-authored by Sara Pistilli, PharmD. and Richard D. Kelly

In Chromadex, Inc., Dartmouth College, v. Elysium Health, Inc., on February 13, 2023, the Federal Circuit affirmed a summary judgement for the asserted claims of US 8,197,807 (the ’807 patent) being directed to unpatentable subject matter under 35 U.S.C. § 101. The invalidity of the claim in question related to the “product of nature” and “law of nature” exceptions to patentability.

The claim in contention recited:

1. A composition comprising isolated nicotinamide riboside in combination with one or more of tryptophan, nicotinic acid, or nicotinamide, wherein said combination is in admixture with a carrier comprising a sugar, starch, cellulose, powdered, tragacanth, malt, gelatin, talc, cocoa butter, suppository wax, oil, glycol, polyol, ester, agar, buffering agent, alginic acid, isotonic saline, Ringer’s solution, ethyl alcohol, polyester, polycarbonate, or polyanhydride, wherein said composition is formulated for oral administration and increases NAD+ biosynthesis upon oral administration.

The original filing of the ’807 patent battled novelty and obviousness objections ending in three allowable claims out of a total of 33 claims presented during prosecution. Claims 2 and 3 respectively further recited, “[t]he nicotinamide riboside [NR] is isolated from a natural or synthetic source” and “[t]he formulation comprises a tablet, troche, capsule, elixir, suspension, syrup, wafer, chewing gum, or food.”

The district court focused its analysis of the alleged infringement on the term, “isolated [NR],” which it interpreted as, “[NR] that is separated or substantially free from at least some other components associated with the source of [NR].” The court furthered that “compositions comprising isolated [NR], a naturally occurring vitamin present in cow milk” were directed towards a natural phenomenon. ChromaDex, the licensee of the ’807 Patent, argued (unsuccessfully) that isolated NR differed from naturally occurring nicotinamide riboside (NR) in stability, bioavailability, purity, and therapeutic efficacy, thus making the claims eligible patent subject matter. The district court concluded that the claims were patent ineligible because the claims applied a patent ineligible law of nature.

The Federal Circuit affirmed that the claims directed towards a bioavailable oral form of NR were patent ineligible because the bioavailable oral form of NR is a naturally occurring product. This decision hinged on a comparison of the claimed invention and natural cow’s milk. Both parties agreed that:

1. Milk is a naturally occurring product and is patent ineligible;

2. Milk contains tryptophan and lactose, a sugar; and

3. Tryptophan in milk treats NAD+ deficiencies.

Therefore, the only difference between at least one embodiment within the scope of the claims in question and natural cow’s milk was that the claims were directed towards “isolated” NR.

In view of Myriad (Ass’n for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. 576 (2013)), the Federal Circuit found the act of isolating NR alone insufficient to make the claims in question patent eligible subject matter, because isolating NR does not make it different from its natural counterpart in structure or function. ChromaDex, the licensee of the ’807 Patent, argued that the claimed “isolated” NR composition was advantageous over natural cow’s milk because the isolated NR increased NAD+ biosynthesis. ChromaDex, the licensee of the ’807 Patent, furthered that “NR in milk does not enhance NAD+ biosynthesis” but rather tryptophan was the source of enhanced NAD+ biosynthesis. The Federal Circuit found this argument unpersuasive, as the claims did not require NR specifically to raise NAD+ biosynthesis. Because an increase in NAD+ biosynthesis was the only therapeutic effect claimed, milk’s ability to increase NAD+ biosynthesis was sufficient to satisfy the claimed effect, despite it accomplishing the claimed effect through a different mechanism.

Next, ChromaDex, the licensee of the ’807 Patent, argued the isolated NR composition patent eligible because it was markedly different from milk. It stated the isolation of NR provided NR in higher concentrations than was found in milk. It furthered the isolated NR was different from its natural counterpart because it was bioavailable due to the lack of NR bound lactalbumin whey protein, present in milk. The Federal Circuit compared this case to Natural Alternatives (Nat. Alts. Int'l, Inc. v. Creative Compounds, LLC, 918 F.3d 1338 (Fed. Cir. 2019)), where an isolated natural product was incorporated into an oral dosage form. The Federal Circuit’s decision in Natural Alternatives stated claims directed towards specific treatment formulations that incorporated natural products could be patent eligible if the formulations had different claimed characteristics and could be used in a manner the natural counterpart could not. Based on this decision, the Federal Circuit stated that the increased bioavailability did not distinguish the claimed composition from milk, as the claims did not require the composition to be bioavailable or to be separated from lactalbumin whey protein. Additionally, the Federal Circuit stated the higher concentrations of NR, when in the isolated form, leading to the increase in NAD+ biosynthesis also did not distinguish the claimed composition from milk because the claims did not require a specific amount or concentration to achieve the claimed therapeutic effect. Thus, the Federal Circuit found that the isolated NR composition lacked any markedly different characteristic from its natural counterpart to make it patent eligible.

This case is a reminder that the isolation of a natural product, without specifically claiming a feature that distinguishes the isolated product from its natural counterpart, is insufficient for subject matter eligibility in the US. Claiming natural products in a patent eligible manner requires that the claim recites a markedly different characteristic from the product of nature in its natural state. Markedly different characteristics can be pharmaceutical functions or activities, chemical properties, functional characteristics, or the like.

In the present case, the Applicants did not sufficiently claim the composition’s characteristics that differentiated it from its natural counterpart. If the Applicants had recited a specific concentration/quantity of isolated NR needed to increase NAD+ biosynthesis, a bioavailability requirement, a need for NR to be separated from lactalbumin whey protein, or a required mechanism for NAD+ biosynthesis—the Federal Circuit likely would have considered the claimed composition as patent eligible subject matter. Although these differences were stated in the ‘807 Patent’s specification, it is the claims that must be directed towards patent eligible subject matter. Applicants attempting to patent a composition that includes a natural product should therefor make sure to include language in the claims that is directed towards a specific characteristic the claimed composition possesses that the naturally occurring counterpart does not.

Claims Directed to Detecting Natural Phenomena Using Conventional Techniques Are Patent Ineligible

22 Feb 2023 00:00:00 -0800

CareDx is the exclusive licensee of U.S. Patents 8,703,652, 9,845,497, and 10,329,607 entitled “Non-Invasive Diagnosis of Graft Rejection in Organ Transplant Patients” owned by Stanford. The patents describe diagnosing or predicting organ transplant status by using methods to detect a donor’s cell-free DNA (“cfDNA”). When an organ transplant is rejected, the recipient’s body, through its natural immune response, destroys the donor cells, thus releasing cfDNA from the donated organ’s dying cells into the blood. The increased levels of donor cfDNA, which occur naturally as the organ’s condition deteriorates, can be detected and used to diagnose the likelihood of an organ transplant rejection. Claim 1 of the ’652 patent reads (simplified):

1. A method for detecting transplant rejection, graft dysfunction, or organ failure, the method comprising:

(a) providing a sample comprising [cfDNA] from a subject who has received a transplant from a donor;

(b) obtaining a genotype of donor-specific polymorphisms to establish a polymorphism profile for detecting donor [cfDNA];

(c) multiplex sequencing of the [cfDNA] in the sample followed by analysis of the sequencing results using the polymorphism profile to detect donor [cfDNA] and subject [cfDNA]; and

(d) diagnosing, predicting, or monitoring a transplant status or outcome of the subject who has received the transplant by determining a quantity of the donor [cfDNA] based on the detection of the donor [cfDNA] and subject [cfDNA] by the multiplexed sequencing, wherein an increase in the quantity of the donor [cfDNA] over time is indicative of transplant rejection, graft dysfunction or organ failure, and wherein sensitivity of the method is greater than 56% compared to sensitivity of current surveillance methods for cardiac allograft vasculopathy (CAV).

Claim 1 of the ’497 patent is similar, except that it recites high-throughput sequencing or digital PCR instead of multiplex sequencing for “determining” the amount of donor cfDNA. Claim 1 of the ’607 patent is also similar, except that it recites selective amplification of the cfDNA by PCR before high-throughput sequencing.

A two-step analysis under Alice/Mayo is used to determine whether a patent claim is directed to patent eligible subject matter. In Step 1, the question is whether the claims are directed to a law of nature, natural phenomenon, or/and abstract idea. If yes, in Step 2 the question is whether the claim elements individually and as a whole contain additional elements that amount to significantly more than the judicial exception (i.e., transform the claim into patent-eligible subject matter). Simply appending well-understood, routine, conventional activities previously known to the industry, specified at a high level of generality, to the judicial exception do not make the claims patent eligible.

Here, the methods in the representative claims essentially have four steps for detecting a donor’s cfDNA in a transplant recipient:

1. “obtaining” or “providing” a “sample” from the recipient that contains cfDNA;

2. “genotyping” the transplant donor and/or recipient to develop “polymorphism” or “SNP” “profiles”;

3. “sequencing” the cfDNA from the sample using “multiplex” or “high-throughput” sequencing; or performing “digital PCR”; and

4. “determining” or “quantifying” the amount of donor cfDNA.

CareDx sued Natera, Inc. (“Natera”) and Eurofins Viracor, Inc. (“Eurofins”), alleging that their transplant rejection tests infringed the patents at issue. Natera and Eurofins moved to dismiss the complaints for failure to state a claim due to lack of patent-eligible subject matter under § 101. The motions to dismiss were referred to a magistrate judge, who recommended that they be denied. The magistrate judge held that the claims were a “purportedly new, unconventional combination of steps” to detect natural phenomena.

The district court vacated the magistrate judge’s recommendation. The court noted that language in the specification of the asserted patents suggested that the patented steps were not new or unconventional and that the “specifications raise[d] doubts about the patents’ validity.” However, the court was cautious about ruling prematurely, and denied the motion to dismiss so that the parties could conduct limited discovery and develop the record on conventionality. After the discovery, Natera and Eurofins moved for summary judgment of ineligibility and the district court granted the motions. The court determined that the asserted claims were directed to natural phenomena, i.e., the presence of donor cfDNA in a transplant recipient and the correlation between donor cfDNA and transplant rejection, and concluded that the claims recited only conventional techniques. CareDx appealed.

On Appeal at the U.S. Court of Appeals for the Federal Circuit (“the Court”) CareDx argued that, regarding Alice/Mayo step one, the patents’ claimed advance was not the discovery of a natural correlation between organ rejection and the donor’s cfDNA levels in the recipient’s blood, but rather improved measurement methods in the claims as superior to the inadequate prior art measurement techniques. CareDx argued that the district court did not properly perform the step one analysis because it concluded that step one was essentially the same as step two and centered on “conventionality”. It asserted that there was no basis in the law for a one-step application of Alice/Mayo. Regarding Alice/Mayo step two, CareDx argued that using digital PCR and next-generation sequencing (“NGS”) to identify and measure donor-specific SNPs was an inventive breakthrough and that the patents claim this specific and useful application.

Natera responded that CareDx’s asserted claims were directed to detecting natural phenomena, the presence of an organ donor’s cfDNA in the blood of a transplant recipient and the correlation between elevated levels of that cfDNA and organ transplant rejection. The claims recited performing this detection using collection and measurement techniques that the specification admitted were conventional and could be used without modifications. According to Natera, the claims were indistinguishable from other diagnostic method claims that the Supreme Court found ineligible in Mayo and the Court found ineligible on multiple occasions. Natera added that the district court properly applied Alice step one and relied on the express use of the word “detecting” to conclude that the claims were directed to a natural phenomenon and that the court properly recognized that Alice step one could overlap with step two. The Court agreed with Natera and Eurofins.

The Court noted that this was not a case involving a method of preparation or a new measurement technique, referring to Illumina, Inc. v. Ariosa Diagnostics, Inc., 952 F.3d 1367, opinion modified by 967 F.3d 1319, 1327 (Fed. Cir. 2020). CareDx did not invent or discover the relationship between donor cfDNA and the likelihood of organ transplant rejection. The patents’ specification also expressly stated that the techniques referred to in the claims were conventional and were well within the skill of art. The Court pointed out that CareDx’s patents applied conventional measurement techniques to detect a natural phenomenon and the claimed methods were indistinguishable from other diagnostic method claims.

The Court pointed to Ariosa that involved claims reciting methods for making a diagnosis of certain fetal characteristics based on detecting paternally inherited cell-free fetal DNA (“cffDNA”) in the blood of a pregnant female. 788 F.3d at 1376. The Court explained that here the claims at issue, as in Ariosa, “boil down to collecting a bodily sample, analyzing the cfDNA using conventional techniques, including PCR, identifying naturally occurring DNA from the donor organ, and then using the natural correlation between heightened cfDNA levels and transplant health to identify a potential rejection, none of which was inventive. The claims here are equally as ineligible as those in Ariosa.”

The Court then explained that CareDx incorrectly characterized “our precedent as limiting the conventionality inquiry to step two. On the contrary, and as the district court recognized, we have repeatedly analyzed conventionality at step one as well” (the Court referred to Athena, 915 F.3d 743, 751 (Fed. Cir. 2019) and Cleveland Clinic, 859 F.3d 1352, 1361 (Fed. Cir. 2017)). “Indeed, we have explained that ‘the two stages are plainly related: not only do many of our opinions make clear that the two stages involve overlapping scrutiny of the content of the claims, but . . . there can be close questions about when the inquiry should proceed from the first stage to the second. Elec. Power Grp., LLC v. Alstom S.A., 830 F.3d 1350, 1353 (Fed. Cir. 2016) (citations omitted).” The Court concluded that “our precedent rejects CareDx’s effort to draw a bright line between the two steps.”

Concerning CareDx’s arguments that the “claimed advance” was an improved method for measuring increases in donor cfDNA in a recipient’s body to identify organ rejection and that the patents’ claims were directed not to natural phenomena, but to improved laboratory techniques (the use of digital PCR, NGS, and selective amplification to more accurately measure donor SNPs of cfDNA in transplant recipients), the Court explained that CareDx did not “actually claim any improvements in laboratory techniques—rather … the actual claims of the patent merely recite the conventional use of existing techniques to detect naturally occurring cfDNA. Furthermore, the specification admits that the laboratory techniques disclosed in the claims require only conventional techniques and off-the-shelf technology.” The Court affirmed that the ’652, ’497, and ’607 patents’ asserted claims were directed to natural phenomena under Alice/Mayo step one.

Regarding Alice/Mayo step two, the Court also agreed that the asserted claims added nothing inventive because they merely recite “standard, well-known techniques in a logical combination to detect natural phenomena.” The Court agreed that the district court had thoroughly considered whether any of the claims’ additional elements were unconventional and, based on the specification’s admissions, properly found that they were not. The Court noted again that the specification admitted that each step in the purported invention required only conventional techniques and commercially available technology. “We have repeatedly held that applying standard techniques in a standard way to observe natural phenomena does not provide an inventive concept.” The Court explained that “[a]s in each of these cases [referring to Ariosa, Athena, Roche], CareDx’s asserted claims add nothing inventive at step two because they recite detection methods that ‘simply append[] conventional steps, specified at a high level of generality’ to natural phenomena.” “Each of the methods in the recited steps was already being performed by those in the art. Furthermore, the claimed combination of steps adds nothing inventive.” “The practice of the asserted method claims does not result in an inventive concept that transforms the natural phenomena into a patentable invention” and affirmed the district court’s holding with regard to Alice/Mayo step two.

The Court held that because the claims in the ’652, ’497, and ’607 patents were directed to a natural law together with conventional steps to detect or quantify the manifestation of that law, they were ineligible under § 101.

The proper claim drafting is essential in the diagnostic field. To be patent-eligible, the claims must be significantly more than an instruction to apply judicial exception using some unspecified/generic/well-known techniques. Conventional technologies can be used in unconventional ways to make the claimed invention patent eligible. Also, specific elements may make claims patent eligible. The invention with a high level of specificity, specific steps/components may lead to patent eligibility of the claim. The claim’s specificity/technical character should be connected to its advance over the prior art.

CareDx, Inc. v. Natera, Inc., 40 F.4th 1371 (Fed. Cir. 2022).

Reasonable Expectation of Success in Treating Different Conditions Not Implied by Structural Similarity

07 Feb 2023 00:00:00 -0800

In the matter of Ex parte Taleb, et al., the Patent Trial and Appeal Board (PTAB) determined on January 31, 2023, that an examiner (James Anderson, supported by Supervisory Patent Examiners, Jeffrey Lundgren and Kortney Klinkel) failed to establish the obviousness of claims by failing to establish a reasonable expectation of success in achieving a claimed result of a method claim. The claim in question recited

[a] method of treating obesity in an obese subject in need thereof, comprising administering to the obese subject a therapeutically effective amount of an indoleamine 2,3-dioxygenase (IDO) inhibitor selected from the group consisting of β-(3-benzofuranyl)-alanine, β-(3-benzo(b)thienyl)-alanine, 6-nitro-tryptophan, 6-fluoro-tryptophan, 4-methyl-tryptophan, 5-methyl tryptophan, 6-methyl-tryptophan, 5-methoxytryptophan, 5-hydroxy-tryptophan, 3,3'-diindolylmethane, 5-Br-4-Cl-indoxyl 1,3-diacetate, 9-vinylcarbazole, acemetacin, 5-bromo-tryptophan, 5-bromoindoxyl diacetate, pyrrolidone dithiocarbamate, and 4-phenylimidazole.

The structures of the claimed compounds are provided below:

The original filing of the appealed application presented four claims, three of which were independent. Original claim 1 recited “[a] method of treating obesity in a subject in need thereof comprising administering to the subject a therapeutically effective amount of an indoleamine[-2,3-]dioxygenase (IDO) inhibitor,” while independent claims 2 and 4 respectively recited methods of “for the prophylactic treatment of an obesity related disease” and “improving insulin sensitivity in an obese subject.”

After novelty rejections of the claims, the applicant amended the claims to recite specific indoleamine-2,3-dioxygenase (IDO) inhibitors, which were further defined after three further office actions containing obviousness rejections, relying at the outset on the primary and tertiary prior art references appealed. The tertiary prior art reference related to the efficacy of 1-methyl tryptophan in reversing IDO-mediated arrest of T-cell proliferation in human epithelial ovarian cancer. The narrowing of the IDO inhibitors eliminated, among other things, 1-methyl tryptophan from the claims.

The rejection of the applicant’s appealed method claim relied upon a combination of five (5) prior art references. The examiner argued that the primary non-patent literature (NPL) reference described several salient details related to treating obesity, namely:

(1) morbid obesity is associated with low-grade systemic inflammation and immune activation, which results in the synthesis and release of pro-inflammatory cytokines, including TNF-α and IFN-γ;

(2) elevated production of TFN-α induces expression of indoleamine 2,3-dioxygenase (IDO), which functions to convert tryptophan into kynurenine;

(3) lowered tryptophan availability from increased kynurenine production affects serotonin production, since tryptophan is a precursor in the synthesis of serotonin, thereby resulting in diminished serotonin in the central nervous system;

(4) decreased serotonin levels increase the susceptibility to mood disturbance, depression and increased appetite; and

(5) quantitative serotonin deficiency can lead to a reward deficiency syndrome that perpetuates pathologic eating, thereby supporting a functional link to obesity.

The examiner relied on a secondary NPL reference for its disclosure of a study of obese and non-obese adolescents finding that serum TNF-α was significantly higher in the obese group than the non-obese group. A tertiary NPL reference relied upon by the examiner described that levo-1-methyl-tryptophan, i.e.,

is an IDO inhibitor and a quaternary NPL reference gave the definition of overweight as a BMI of 25.0 to 29.9. The fifth prior art NPL reference was relied on for a disclosure that 1-methyl-tryptophan and (among others) several other recited compounds, i.e., β-(3-benzofuranyl)-DL-alanine, β-(3-benzo(b)thienyl)-DL-alanine, 6-nitro-L-tryptophan, 3,3'-diindolylmethane, 5-Br-4-Cl-indoxyl 1,3-diacetate, 9-vinylcarbazole, acemetacin, 5-bromo-DL-tryptophan, and 5-bromoindoxyl diacetate, are IDO inhibitors.

The applicant had initially also claimed 1-methyl-tryptophan, but removed 1-methyl-tryptophan from the claim to attempt to define over the combined cited art. The applicant argued the lack of predictability of maintaining the effect of 1-methyl-tryptophan using the different active ingredients from the fifth prior art NPL reference, which:

cites various IDO inhibitors but does not teach intervention in inflammatory disease or obesity and/or obesity-related diseases. Thus, the biological outcome of the use of each as a treatment for obesity and/or obesity-related disorders cannot be predicted based on the chemical structures of the various inhibitors. One of ordinary skill in the art would recognize that minor changes in constituents of a family chemical structures can dramatically change the binding and efficacy between those family members. Therefore, it is not obvious that IDO inhibitors effective for neurological disorders would also be effective for treating obesity and/or obesity-related disorders.

The examiner maintained on appeal that it would have been obvious to administer an IDO inhibitor to treat or inhibit obesity because (i) the primary NPL reference teaches that immune activation resulting in increased TNF-α and systemic inflammation in obesity causes elevated expression of IDO, an effect that reduces circulating serotonin by utilizing tryptophan - a serotonin synthesis precursor - for forming kynurenine, thereby increasing appetite, and (ii) the secondary NPL reference teaches that elevated TNF-α is observed in overweight subjects. The examiner felt that this established that overweight subjects would exhibit elevated IDO expression as a result of increased TNF-α.

The examiner argued that inhibiting IDO would have been expected to minimize tryptophan depletion, thereby promoting serotonin synthesis, which increase serotonin. Deficiency in serotonin was known to lead to pathologic eating due to increased appetite, thus the examiner argued that increasing serotonin levels would have reasonably expected to inhibit obesity in such subjects.

The applicant / appellant argued that the primary NPL reference teaches that elevated production of IFN-γ induces expression of IDO, and that TNF-α is expressed because of IDO expression, not as a cause, and further that the primary NPL reference teaches that leptin, ghrelin, TGF-β, IL-1, IL-6, IL-8, IL-10, haptoglobin, factors of the complement cascade, chemoattractant cytokines, neopterin, cyclohydrolase, all play a role in the chronic immune activation that affects obesity. That is, the applicant / appellant argued the opposite effect would have been expected by IDO inhibition, and that many factors besides IDO affected obesity.

The PTAB found that the primary prior art NPL reference in fact stated that IDO-mediated tryptophan degradation due to chronic immune activation can be considered as the driving force for food intake in obese subjects, but that this suggestion depended on a string of inferences. The PTAB noted the examiner’s citations, but pointed to the conclusion in the primary NPL reference that

[a]ccumulating evidence suggests that IDO might be an important contributing factor to the complex pathophysiology [sic] of morbid obesity that links the immune system with central regulators of hunger, satiety and mood disturbances and thus can be considered as a novel scientific target that deserves further investigation in the urgent need to treat overweight [subjects].

The PTAB found that the primary prior art NPL reference described a hypothesis connecting IDO activity to obesity, but lacked evidence supporting the theory that increased IDO activity causesobesity, and provides no evidence showing that IDO expression or activity is higher in obese subjects than in lean subjects, or that increased IDO activity causes decreased serotonin levels in obese subjects, or that lower serotonin levels cause subjects to overeat, or that inhibiting IDO activity causes serotonin levels to rise and, ultimately, causes subject to eat less and lose weight.

The PTAB found that no other cited reference established this link, and that the fifth prior art NPL reference merely showed the treatment of other conditions by IDO inhibition. Therefore the PTAB was persuaded that there was no reasonable expectation of successfully treating obesity or obesity-related symptoms with the compounds in the appealed claims. Accordingly, the obviousness rejection was reversed.

This case is a reminder that, particularly for method claims in which a specific medicinal or therapeutic effect is claimed, structural similarity is generally insufficient to extrapolate efficacy to structurally related compounds for which that medicinal or therapeutic effect is unknown. The pharmaceutical chemical art is still treated as unpredictable by the PTAB, even if the examining corps does not as deferentially consider this fact.