biotech patents and section 101 rejections: meeting patent...

Biotech Patents and Section 101 Rejections:

Meeting Patent Eligibility RequirementsLeveraging Recent Decisions and USPTO Guidance to Overcome Rejections

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TUESDAY, FEBRUARY 12, 2019

Presenting a live 90-minute webinar with interactive Q&A

Amanda K. Murphy, Ph.D., Partner, Finnegan Henderson Farabow Garrett & Dunner, Washington, D.C.

Steven P. O'Connor, Ph.D., Partner, Finnegan Henderson Farabow Garrett & Dunner, Reston, Va.

Sanya Sukduang, Partner, Finnegan Henderson Farabow Garrett & Dunner, Washington, D.C.

Sara A. Leiman, Ph.D., Attorney, Finnegan Henderson Farabow Garrett & Dunner, Boston

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5

Section 101 – The Basics

“Whoever invents or discovers any new and useful

process, machine, manufacture, or composition of

matter, or any new and useful improvement thereof,

may obtain a patent therefor, subject to the conditions

and requirements of this title.” 35 U.S.C. §101

Exceptions: “laws of nature, physical

[natural] phenomena, and abstract ideas”

Bilski; citing Diamond v. Chakrabarty

6

Section 101

Mayo/Alice Two Step

Step 1: Claims directed to patent ineligible subject matter?

(i.e., law of nature, natural phenomena, or abstract idea)

• No → End of analysis

• Yes → Move to Step 2

Step 2: Search for an inventive concept

• Identify non-patent-ineligible elements of the claim.

• Consider these elements both individually and as an ordered

combination.

• Do the additional elements “transform the nature of the claim”

into a patent eligible-application?

7

“§101 Success By Subject Matter”

Source: Docketnavigator Plus Special Report, “Alice Through the Looking Glass,” Jan. 2019.

8

56% Success Rate66% Success Rate60% Success Rate

“§101 Success By Litigation Stage”


9

“§101 Success By Litigation Stage and Patent

Classification”


10

Success of §101 Motions

Varies Considerably by Court

Source: Based on chart in Docketnavigator Plus Special Report, “Alice Through the Looking Glass,” Jan. 2019;

win rate based on motions asserting a s. 101 challenge that were granted or partially granted; not technology-

specific.

58%59/102

48%36/75

67%41/61

67%34/51

74%17/23

84%16/19

83%10/12

57%4/7

43%3/7

100%4/4

0%

10%

20%

30%

40%

50%

60%

70%

80%

90%

100%

D Del ED Tex ND Cal CD Cal ND Ill ED Va SDNY D NJ WD Tex MD Fla

11

Which Step is Lacking in Unsuccessful § 101

Challenges

12


§ 101 Challenges: PTAB PGR/CBM Petitions


13

Federal Circuit Post-Alice

111 Federal Circuit decisions involving challenges to patents under Alice.

Federal Circuit invalidation rate = 91% (101/111)

100%9/9

67%2/3

30%

40%

50%

60%

70%

80%

90%

100%

Wallach, Hughes Newman, O'Malley

Rate of invalidation under § 101

Source: Matthew Bullman, “Patents Are Surviving Challenges Under Alice More Often,: Law360 (Sept. 25, 2017)https://www.law360.com/ip/articles/966126/patents-are-surviving-challenges-under-alice-more-often?nl_pk=72a5af6d-8bfa-40dd-866d-e47ede53dd7f&utm_source=newsletter&utm_medium=email&utm_campaign=ip

Case Law and USPTO Updates

• Pre-Vanda CAFC, District Court, and PTAB decisions

• Vanda v. West-Ward

• Post-Vanda changes to USPTO guidance on 101

• Post-Vanda CAFC, District Court, and PTAB decisions

15

Federal Circuit – Pre-Vanda

Patent Ineligible

Genetic Technologies v. Merial, LLC, 818 F.3d 1369 (Fed. Cir.

2016) – method of detecting an allele

Cleveland Clinic v. True Health Diagnostics, LLC, 859 F.3d

1352 (Fed. Cir. 2017) – diagnostic methods

Patent Eligible

Rapid Litigation v. CellzDirect, 827 F.3d 1042 (Fed. Cir.

2016) – method of producing cryopreserved hepatocytes

16

Patent Ineligible

Genetic Technologies v. Merial

1. A method for detection of at least one coding region allele of a multi-allelic genetic locus comprising: a) amplifying genomic DNA with a primer pair that spans a non-

coding region sequence, said primer pair defining a DNA sequence which is in genetic linkage with said genetic locus and contains a sufficient number of non-coding region sequence nucleotides to produce an amplified DNA sequence characteristic of said allele; and

b) analyzing the amplified DNA sequence to detect the allele.

CAFC: Affirmed ineligible - claim directed to a law of nature. • Describes a natural phenomenon.• No sufficient “inventive concept” to provide subject matter

eligibility. • “Amplifying” and “analyzing” were well known, routine, and

conventional.

17

Patent Ineligible

Cleveland Clinic v. True Health Diagnostics

Three of the four patents-in-suit directed to methods of diagnosing cardiovascular disease based on testing for myeloperoxidase.

District court held that claims of the testing patents were patent ineligible.

CAFC: Affirmed ineligible - claims directed to a law of nature.

• “The claims of the testing patents are directed to multistep methods for observing the law of nature that MPO correlates to cardiovascular disease.”

• “[W]ell-known technique to execute claimed method.”

• Claim steps merely tell those interested in the correlation.

• “the testing patents here do not extend their discovery that MPOcorrelates to cardiovascular risk to a patentable method.”

18

Patent Eligible

Rapid Litigation v. CellzDirect

1. A method of producing a desired preparation of multi-cryopreserved hepatocytes, said hepatocytes being capable of being frozen and thawed at least two times, …, said method comprising:• subjecting hepatocytes …to density gradient fractionation to separate viable

hepatocytes from nonviable hepatocytes, • recovering the separated viable hepatocytes, and • cryopreserving….

CAFC: Vacated and remanded. Patent-eligible subject matter under §101.• Inventors “create[d] a new and improved way of preserving hepatocyte cells for

later use.”• Claims focused on a process with steps for achieving this desired outcome,

not simply an observation or detection of the ability of hepatocytes to survive multiple freeze-thaw cycles.

• Distinguishable from type of claims held patent-ineligible in Myriad (well-known process) and Ariosa (patent ineligible natural product).

19

District Court: Patent Ineligible, Pre-Vanda

Esoterix Genetic Labs., LLC v. Qiagen Inc., 2016 WL 4555613

(D. Mass. Aug. 31, 2016) – methods of predicting drug efficacy; kits

*Boehringer Ingelheim Pharm., Inc v. HEC Pharm Co., 2016 WL

7177704 (D.N.J. Dec. 8, 2016) – methods of treatment/disease

prevention

*Nat. Alternatives Int'l, Inc. v. Creative Compounds, LLC, 2017 WL

3877808 (S.D. Cal. Sept. 5, 2017) – supplements; method of

regulating hydronium ion concentrations

*Mallinckrodt Hosp. Prod. IP Ltd. v. Praxair Distribution, Inc., 2017

WL 3867649 (D. Del. Sept. 5, 2017) – methods of treatment

20

* On Appeal

1. A method for determining an increased likelihood of

pharmacological effectiveness of treatment by gefitinib or erlotinib

in an individual diagnosed with non-small cell lung cancer

comprising: obtaining DNA from a non-small cell lung cancer

tumor sample from the individual; and determining the presence or

absence of at least one nucleotide variance . . .

District court held the claims invalid as directed to a law of nature

and lacking anything “transformative”:

• Claims identify a law of nature explaining why a known cancer

treatment is more effective for a certain population of patients

• Claims merely tell physicians to “apply” that law of nature by

testing for the relevant mutations using methods well known in

the art

Patent Ineligible

Esoterix Genetic Labs., LLC v. Qiagen Inc.

1. A kit comprising:

(a) at least one nucleic acid probe designed to detect a nucleotide

variance within exons 18, 19, 20 or 21 of the EFGR gene,

wherein detection is based on specific hybridization to the

nucleotide variance sequence,. . .wherein the nucleic acid probe

comprises a detectable label;

(b) products and reagents required to carry out an annealing

reaction; and

(c) instructions.

District court held the kit claims were “method claims in the guise

of a device”

• In practical effect cover the same invention as the method claims

(discovery of a natural correlation)

Patent Ineligible

Esoterix Genetic Labs., LLC v. Qiagen Inc.

Patent Ineligible

Boehringer Ingelheim Pharm., Inc v. HEC Pharm Co.

Appeal filed Nov. 2018

1. A method of treating and/or preventing metabolic diseases in a

patient for whom metformin therapy is inappropriate due to at least

one contraindication against metformin comprising orally

administering to the patient a DPP-IV inhibitor wherein the

contraindication is selected from the group consisting of: . . .

District court distinguished CellzDirect on basis that the ’156

patent claims recite a single instruction of “orally administering” a

DPP-IV inhibitor, rather than a series of steps tied to tangible

embodiments

District court concluded that claims of the ’156 patent are directed

to an abstract idea: the discovery that DPP-IV inhibitors of the

patent are mainly excreted via the liver

District court stated that the ’156 patent provides no contribution

over conventional knowledge of administering DPP-IV inhibitors

and instruction to physicians is a mental process

24

Patent Ineligible

Boehringer Ingelheim Pharm., Inc v. HEC Pharm Co.

Patent Ineligible

Nat. Alternatives Int'l, Inc. v. Creative Compounds

Appeal filed Dec. 2017 - Representative Claims (different patents):

A human dietary supplement, comprising a beta-alanine in a unit dosage

of between about 0.4 grams to 16 grams . . .

A human dietary supplement for increasing human muscle tissue strength

comprising a mixture of creatine, a carbohydrate and free amino acid

beta-alanine that is not part of a dipeptide, polypeptide or an

oligopeptide, . . .

A method of regulating hydronium ion concentrations in a human tissue

comprising: providing an amount of beta-alanine to blood or blood

plasma effective to increase beta-alanylhistidine dipeptide synthesis . . .

and exposing the tissue to the blood or blood plasma . . .

25

District court focused on the fact that beta-alanine is an amino acid

naturally present in human and other vertebrate muscle, and that

the specification of the patent “acknowledges that placing a natural

substance into a dietary supplement to increase the function of

tissues is conventional activity”

District court held that achieving unnaturally high levels of

carnosine synthesis through the dietary supplement does not

render the claims patent-eligible, as doing so merely applies the

same natural law and relies on the human body to do the work.

District court found the method claim invalid as directed to patent-

ineligible subject matter for taking a natural phenomenon and

“add[ing] the words apply it to human tissue.”

26

Patent Ineligible

Nat. Alternatives Int'l, Inc. v. Creative Compounds

Patent Ineligible

Mallinckrodt Hosp. Prod. IP Ltd.

v. Praxair Distribution, Inc.

Appeal filed Oct 2017

1. A method of treating patients who are candidates for inhaled

nitric oxide treatment, . . . comprising: (a) identifying a plurality of

term or near-term neonatal patients who have hypoxic respiratory

failure and are candidates for 20 ppm inhaled nitric oxide

treatment; (b) determining that a first patient of the plurality does

not have left ventricular dysfunction; (c) determining that a second

patient of the plurality has left ventricular dysfunction . . . ; (d)

administering 20 ppm inhaled nitric oxide treatment to the first

patient; and (e) excluding the second patient from treatment with

inhaled nitric oxide . . . .

27

District court held that the core of the invention “is really a patient

populations' natural physiological response to 20 ppm of inhaled nitric

oxide treatment,” which is a natural phenomenon.

District court found that the claims fail to make a transformative

contribution, as the method of identifying the target patient population

was routine in the art and nitric oxide was already an established

treatment.

District court equated the “excluding” step of subpart (e) to the

“wherein” clauses in Mayo, finding that this step merely tells physicians

how to apply a law of nature, and further analogized the claims to those

in invalidated in Cleveland Clinic, as predicting patient risk “‘with no

meaningful non-routine steps in between.’”

28

Patent Ineligible

Mallinckrodt Hosp. Prod. IP Ltd.

v. Praxair Distribution, Inc.

District Court – Pre-Vanda

Patent Eligible

Idexx Labs., Inc. v. Charles River Labs, Inc., 2016 WL 3647971 (D.

Del. Jul. 7, 2016) - methods of blood collection from rodents

*Vanda Pharm, Inc. v. Roxane Labs., Inc., 2016 WL 4490701 (D. Del.

Aug. 25, 2016) - methods of treatment

29

* Appealed

Patent Eligible

Idexx Labs., Inc. v. Charles River Labs, Inc.

Motion to dismiss denied

1. A method of determining a presence or absence of an infectious

disease in a population of rodents, the method comprising: (a) providing

a plurality of blood collection cards to a user . . . (b) providing

instructions to the user comprising the following: (i) draw blood from an

individual rodent; (ii) apply the blood to one of the plurality of blood

collection cards; (iii) allow the blood sample to dry on the collection card;

(iv) repeat steps i, ii, and iii . . . ; and (v) transport the plurality of

collection cards to a laboratory as a single unit; (c) receiving the plurality

of collection cards as a single unit from the user, (d) extracting dried

blood from the cards; (e) analyzing the extracted blood . . . ; and (f)

reporting the results of the presence or absence of the infectious disease

to the user.

District court held that “when examined as an ordered combination

of limitations,” the claims describe a “specific, novel

implementation of the abstract idea of collecting, analyzing, and

reporting.”

District court noted the improvements represented by the claimed

invention: permitting monitoring of a rodent population without

euthanizing animals, waiting for blood to clot in a centrifuge, or

shipping blood serum samples overnight in a refrigerated

container.

31

Patent Eligible

Idexx Labs., Inc. v. Charles River Labs, Inc.

32

1. A method for treating a patient with iloperidone, wherein the patient is suffering from schizophrenia, the method comprising the steps of:• determining whether the patient is a CYP2D6 poor metabolizer by:

• obtaining or having obtained a biological sample from the patient;• and performing or having performed a genotyping assay on the

biological sample to determine if the patient has a CYP2D6 poor metabolizer genotype; and

• if the patient has a CYP2D6 poor metabolizer genotype, then internally administering iloperidone to the patient in an amount of 12 mg/day or less, and if the patient does not have a CYP2D6 poor metabolizer genotype, then internally administering iloperidone to the patient in an amount that is greater than 12 mg/day, up to 24 mg/day,

• wherein a risk of QTc prolongation for a patient having a CYP2D6 poor metabolizer genotype is lower following the internal administration of 12 mg/day or less than it would be if the iloperidone were administered in an amount of greater than 12 mg/day, up to 24 mg/day.

Patent Eligible

Vanda Pharm, Inc. v. Roxane Labs., Inc.

District court held that claims are directed to laws of nature

• “The claims depend on the [natural] relationship between

iloperidone, CYP2D6 metabolism, and QTc prolongation.”

BUT District court distinguished Mayo because the dosage adjustment

steps of Vanda’s patent were not routine and conventional activity

• Dosage steps require applying genetic tests in a highly specified

way

• Process of using the claimed genetic test to inform dosage

adjustment not routine and conventional

Holding: Claims amount to more than a routine application of a

natural law, and are directed to patent eligible subject matter

33

Patent Eligible

Vanda Pharm, Inc. v. Roxane Labs., Inc.

PTAB: Patent Ineligible, Pre-Vanda

Ex Parte Manolescu, APPEAL 2014-000655, 2016 WL

6819066 (PTAB Nov. 16, 2016) - diagnostic methods

Ex Parte Vogelstein, APPEAL 2014-006244, 2016 WL

7046652 (PTAB Nov. 28, 2016) - diagnostic methods

Ex Parte Agan, APPEAL 2015-001596, 2016 WL 7175317

(PTAB Nov. 30, 2016) - diagnostic methods

*Ex Parte Axtell, APPEAL 2015-003156, 2016 WL 7175327

(PTAB Nov. 30, 2016) – methods of assessing prognosis,

methods of treatment

Ex Parte Goronzy, APPEAL 2015-000312, 2016 WL 7210590

(PTAB Dec. 8, 2016) - diagnostic methods

34

Ex Parte Penn, APPEAL 2015-006953, 2016 WL 7210600


Ex Parte Murphy, APPEAL 2015-005591, 2016 WL 7487305


*Ex Parte Chamberlain, APPEAL 2014-009849, 2017 WL

244123 (PTAB Jan. 18, 2017) – methods of treatment

Ex Parte Theodoor, APPEAL 2016-003313, 2017 WL 430834

(PTAB Jan. 27, 2017) - diagnostic methods

Ex Parte Zanger, APPEAL 2015-006154, 2017 WL 476028


35


Ex Parte Penger, APPEAL 2015-007994, 2017 WL 476039


*Ex Parte Hayes, APPEAL 2015-000614, 2017 WL 605092

(PTAB Feb. 13, 2017) – compositions

Ex Parte Park, APPEAL 2015-007714, 2017 WL 745073r

(PTAB Feb. 21, 2017) - diagnostic methods

Ex Parte Weibrecht, APPEAL 2016-003523, 2017 WL

1032612 (PTAB Mar. 14, 2017) - process

36


*Ex Parte McBride, APPEAL 2015-006282, 2016 WL 7097705

(PTAB Dec. 1, 2016) - compositions

*Ex Parte Terbrueggen, APPEAL 2017-001359, 2017 WL

462099 (PTAB Jan. 13, 2017) – detection methods

37

PTAB: Patent Eligible, Pre-Vanda

Patent Ineligible - Ex Parte Axtell

1. A method for assessing prognosis for responsiveness of a human

multiple sclerosis patient to an IL-17 inhibitor, comprising:

analyzing a blood sample from said patient with an antibody-based

assay for the presence of IL-17F and IL-7 . . . assessing

responsiveness to an IL-17 inhibitor . . . and providing to the

multiple sclerosis patient an assessment of the prognosis for

responsiveness to an IL-17 inhibitor.

14. The method of Claim 1, further comprising administering an IL-

17 inhibitor to a patient assessed as a responder to IL-17

inhibitors.

PTAB analogizes these claims to claims 2 and 6 of USPTO’s Life

Sciences Subject Matter Eligibility Guidance - Example 29

38

Example 29: Diagnosing and Treating Julitis

• Applicant found that the presence of a particular protein

“JUL-1” is indicative of a particular skin disease (julitis)

• Unclear from fact pattern whether JUL-1 was previously

known or newly discovered along with the discovery of its

association with julitis

• Julitis patients were sometimes misdiagnosed as having

rosacea (rosacea treatments are ineffective against julitis)

• Julitis traditionally treated with anti-TNF antibodies

39

Example 29, Claims 2 and 6, Pre-Vanda

2. A method of diagnosing julitis in a patient, said method comprising:

a. obtaining a plasma sample from a human patient; b. detecting

whether JUL-1 is present in the plasma sample by contacting the plasma

sample with an anti-JUL-1 antibody and detecting binding between JUL-

1 and the antibody; and c. diagnosing the patient with julitis when the

presence of JUL-1 in the plasma sample is detected.

6. A method of diagnosing and treating julitis in a patient, said method

comprising: a. obtaining a plasma sample from a human patient; b.

detecting whether JUL-1 is present in the plasma sample; c. diagnosing

the patient with julitis when the presence of JUL-1 in the plasma sample

is detected; and d. administering an effective amount of anti-tumor

necrosis factor (TNF) antibodies to the diagnosed patient.

40


1. A method for assessing prognosis for responsiveness of a human

multiple sclerosis patient to an IL-17 inhibitor, comprising:

analyzing a blood sample from said patient with an antibody-based

assay for the presence of IL-17F and IL-7 . . . assessing

responsiveness to an IL-17 inhibitor . . . and providing to the

multiple sclerosis patient an assessment of the prognosis for

responsiveness to an IL-17 inhibitor.

14. The method of Claim 1, further comprising administering an IL-

17 inhibitor to a patient assessed as a responder to IL-17

inhibitors.

41


PTAB held that “Claim 1 in this appeal has the same ineligibility

deficit as in claim 2 of Example 29” – drawn to a mental step

(assessing/providing an assessment)

PTAB notes that claim 14 (like claim 6 of Example 29) includes

diagnosis steps but adds a treatment step, however:

“The steps recited in rejected claim 14, however, do not ensure

accurate differential diagnosis between two diseases as they did in

claim 6 of Example 29. Rather, claim 14 involves administering a

known drug to the same class of accurately diagnosed patient. The

patients are the same; the drug is the same; the only difference is

the knowledge of the natural law which enables a doctor to

administer the drug to patients responsive to the drug.”

42

Patent Ineligible - Ex Parte Chamberlain

1. A method of treating a human individual having a bone disorder,

the method comprising: determining in a nucleic acid sample . . .

the presence of a TT genotype at a single nucleotide polymorphism

rs2297480 . . . in the farnesyl diphosphate synthase (FDPS) gene,

the presence of the TT genotype at SNP rs2297480 being indicative

that the individual is responsive to bisphosphonates; and

administering a bisphosphonate to the individual if the TT genotype

is present.

PTAB held claim 1 invalid as directed to a law of nature, and

because administering bisphosphonate to treat a bone disorder is

routine in the art.

43

Patent Ineligible - Ex Parte Hayes

13. A liquid formulation comprising (a) an oligonucleotide

consisting of Seq ID No. 1 . . And (b) an aqueous carrier comprising

an aggregation-preventing compound selected from the group

consisting of mono and disaccharides and/or sugar alcohols,

wherein the amount of the aggregation-preventing compound is

sufficient to solubilize the oligonucleotide and maintain it in

solution without aggregation for a period in excess of 6 hours at

room temperature, wherein the oligonucleotide is a present in the

formulation at a concentration of at least 25 mg/ml.

PTAB held claim 13 invalid because the claim requires a native

sequence and “[t]he use of sugars and sugar alcohols to prevent

agglomeration of DNA fragments was well known in the art.”

44

Patent Eligible - Ex Parte McBride

1. A composition comprising an isolated polypeptide . . . wherein

the isolated polypeptide is bound to a solid support or a detectable

label.

36. An isolated antibody . . . wherein the antibody is either bound

to a solid support or a detectable label.

PTAB held:

• Polypeptide (or antibody) bound to a solid support or detectable

forms a new non-natural composition

• Claimed subject matter is not directed to a natural product.

45

Patent Eligible - Ex Parte Terbrueggen

1. A method for detecting a plurality of different target nucleic

acids in a sample, wherein each target nucleic acid comprises a first

target domain adjacent to a second target domain and a third

target capture domain located upstream or downstream from said

first and second target domains, said method comprising: (a)

providing a plurality of ligation substrates . . . (b) ligating said first

and second ligation probes without the use of a ligase enzyme to

form a first plurality of ligation products; (c) hybridizing target

capture probes comprising a capture moiety to said third target

domain of said target nucleic acids to form target complexes;

(d) capturing said target complexes on a surface using said capture

moiety; (e) amplifying said ligation products to form amplicons; (f)

detecting said amplicons, thereby detecting said target nucleic

acids.

46

Patent Eligible - Ex Parte Terbrueggen

PTAB found:

• Claim 1 requires concrete physical steps

• Ex: Step (f) requires “actual physical detection of amplified

nucleic acids” (specification lists suitable detection techniques)

• Thus, the claimed detecting step is not an abstract idea

• “Examiner did not properly evaluate the claimed invention as a

whole in determining that the claimed process recited nothing

more than the use of conventional steps to implement the

alleged abstract idea of detecting target nucleic acids in a

sample.”

47

Vanda at the Federal Circuit

48

Patent Eligible - Vanda Pharms. v. West-Ward

Pharms., 887 F.3d 1117 (Fed. Cir. 2018)

49

1. A method for treating a patient with iloperidone, wherein the patient is suffering from schizophrenia, the method comprising the steps of:• determining whether the patient is a CYP2D6 poor metabolizer by:

• obtaining or having obtained a biological sample from the patient;• and performing or having performed a genotyping assay on the

biological sample to determine if the patient has a CYP2D6 poor metabolizer genotype; and

• if the patient has a CYP2D6 poor metabolizer genotype, then internally administering iloperidone to the patient in an amount of 12 mg/day or less, and if the patient does not have a CYP2D6 poor metabolizer genotype, then internally administering iloperidone to the patient in an amount that is greater than 12 mg/day, up to 24 mg/day,

• wherein a risk of QTc prolongation for a patient having a CYP2D6 poor metabolizer genotype is lower following the internal administration of 12 mg/day or less than it would be if the iloperidone were administered in an amount of greater than 12 mg/day, up to 24 mg/day.

Patent Eligible - Vanda Pharm, Inc. v. Roxane Labs.,

Inc., 2016 WL 4490701 (D. Del. Aug. 25, 2016)

District court held that claims are directed to laws of nature

• “The claims depend on the [natural] relationship between

iloperidone, CYP2D6 metabolism, and QTc prolongation.”

BUT District court distinguished Mayo because the dosage

adjustment steps of Vanda’s patent were not routine and

conventional activity

• Dosage steps require applying genetic tests in a highly

specified way

• Process of using the claimed genetic test to inform

dosage adjustment not routine and conventional

50

CAFC: Affirmed. Patent-eligible subject matter under §101.

“Claim 1 requires specific steps: (1) determining the patient's CYP2D6metabolizer genotype by (a) obtaining a biological sample and (b) performing a genotyping assay; and (2) administering specific dose ranges of iloperidone depending on the patient's CYP2D6 genotype.”

“directed to a method of using iloperidone to treat schizophrenia. The inventors recognized the relationships between iloperidone, CYP2D6 metabolism, and QTc prolongation, but that is not what they claimed. They claimed an application of that relationship.”

“directed to a specific method of treatment for specific patients using a specific compound at specific doses to achieve a specific outcome. . . . They recite more than the natural relationship between CYP2D6 metabolizer genotype and the risk of QTc prolongation. Instead, they recite a method of treating patients based on this relationship that makes iloperidone safer”

51

Patent Eligible - Vanda Pharms. v. West-Ward

Pharms., 887 F.3d 1117 (Fed. Cir. 2018)

USPTO Memo: Recent Subject Matter

Eligibility Decision: Vanda (June 7, 2018)

• Federal Circuit evaluated claims as a whole to determine what claim is “directed to”

• Method of treatment claims that apply a natural relationship should pass step 2A (claim “directed to” patent eligible subject matter)

• No consideration of “routine or conventional” activity in step 2B when eligibility determined as “yes” in step 2A

52

Updated Subject Matter Eligibility Examples:

Life Sciences

https://www.uspto.gov/sites/default/files/documents/ieg-may-

2016-ex.pdf

•Example 28 Vaccines

•Example 29 Diagnosing and Treating Julitis

Corrected in USPTO memo on Vanda

•Example 30 Dietary Sweeteners

•Example 31 Screening for Gene Alterations

•Example 32 Paper-Making Machine

•Example 33 Hydrolysis of Fat

53

Example 29: Diagnosing and Treating Julitis

• Applicant found that the presence of a particular protein

“JUL-1” is indicative of a particular skin disease (julitis)

• Unclear from fact pattern whether JUL-1 was previously

known or newly discovered along with the discovery of its

association with julitis

• Julitis patients were sometimes misdiagnosed as having

rosacea (rosacea treatments are ineffective against julitis)

• Julitis traditionally treated with anti-TNF antibodies

• Applicant discovered it is possible to treat julitis with

topical vitamin D

54

Post-Vanda, these claims pass Step 2A

5. A method of diagnosing and treating julitis in a patient, said

method comprising: a. obtaining a plasma sample from a human

patient; b. detecting whether JUL-1 is present in the plasma

sample; c. diagnosing the patient with julitis when the presence of

JUL-1 in the plasma sample is detected; and d. administering an

effective amount of topical vitamin D to the diagnosed patient.

6. A method of diagnosing and treating julitis in a patient, said

method comprising: a. obtaining a plasma sample from a human

patient; b. detecting whether JUL-1 is present in the plasma

sample; c. diagnosing the patient with julitis when the presence of

JUL-1 in the plasma sample is detected; and d. administering an

effective amount of anti-tumor necrosis factor (TNF) antibodies to

the diagnosed patient.

55

Section 101

New USPTO Guidance

USPTO released “2019 Revised Patent Subject Matter Eligibility Guidance”

Effective Jan. 7, 2019. Public comments requested by March 8, 2019.

Step 1: Are the claims directed to statutory patent eligible subject matter

(process, machine, manufacture, or composition of matter)?

• Yes → Move to Step 2

• No → End of analysis (claim does not recite patent-eligible subject

matter)

56

Step 2:

2A, Prong 1: Does the claim recite a judicial exception?

• “basic tool of scientific and technological work,” i.e., law of nature,

natural phenomena, or abstract idea)

2A, Prong 2: Does the claim integrate the judicial exception into a

practical application?

• Clarifies that a claim “reciting” a judicial exception does NOT equate to

a claim “directed to” a judicial exception

• Yes → End of analysis (patent-eligible subject matter)

• No → Go to 2B.

2B. Search for an inventive concept (if Yes → patent-eligible)

• Do the additional elements “transform the nature of the claim” into a

patent eligible-application?

• Are the additional elements “well-understood, conventional, or routine”?

57

Section 101

New USPTO Guidance

USPTO Quick Reference Sheet

58

USPTO Quick Reference Sheet

59

Court and PTAB decisions after Vanda

60

CAFC and District Court decisions

Post-Vanda

Patent Ineligible

Roche Molecular Sys., Inc. v. Cepheid, 905 F.3d 1363 (Fed. Cir.

2018) – methods for detecting M. tuberculosis

Athena Diagnostics, Inc. v. Mayo Collaborative Servs., LLC, 17-2508

(Fed Cir. 2019) - diagnostic methods

Genetic Veterinary Sciences, Inc. v. LABOklin GmbH & Co., KG, 314

F.Supp.3d 727 (E.D. Va. May 14, 2018) – genotyping methods

Patent Eligible

In re Biogen '755 Patent Litigation, 335 F.Supp.3d 688 (DNJ Sept 7,

2018) – methods of treatment or immunomodulation

Pernix Ireland Pain DAC v. Alvogen Malta Operations Ltd., 2018 WL

2768655 (D. Del. June 8, 2018) – methods of treatment

61

Patent Ineligible

Roche Molecular Sys., Inc. v. Cepheid (Fed. Cir.)

1. A method for detecting Mycobacterium tuberculosis in a biological

sample suspected of containing M. tuberculosis comprising:

a) subjecting DNA from the biological sample to polymerase chain reaction

[PCR]… to produce an amplification product…and

b) detecting the presence or absence of an amplification product[.]

17. A primer having 14–50 nucleotides that hybridizes under hybridizing

conditions to an M. tuberculosis rpoB [gene] …

CAFC: Affirmed ineligible.• “Roche’s primers are indistinguishable from their corresponding

nucleotide sequences on the naturally occurring MTB rpoB gene.”• PCR is a well-known and routine process that did not convert the

method claim to eligible subject matter.• Distinguished from Vanda at not directed to methods of treatment

62

1. A method for diagnosing neurotransmission or developmental

disorders related to muscle specific tyrosine kinase (MuSK) in a

mammal comprising the step of detecting in a bodily fluid of said

mammal autoantibodies to an epitope of muscle specific tyrosine

kinase (MuSK).

7. A method according to claim 1, comprising contacting MuSK or

an epitope or antigenic determinant thereof having a suitable label

thereon, with said bodily fluid, immunoprecipitating any

antibody/MuSK complex or antibody/MuSK epitope or antigenic

determinant complex from said bodily fluid, monitoring for said label

. . ., wherein the presence of said label is indicative of [a MuSK-

related disorder].”

63

Patent Ineligible

Athena Diagnostics, Inc. v. Mayo Collaborative Servs.

(Fed. Cir.)

CAFC: Affirmed ineligible.• “Here, [the natural law] is the correlation between the presence of

naturally-occurring MuSK autoantibodies in the bodily fluid and MuSKrelated neurological diseases like MG. This correlation exists in nature apart from any human action.”

• “[W]e reaffirm that use of a man-made molecule [a label] in a method claim employing standard techniques to detect or observe may still leave the claim directed to a natural law.”

• Distinguished from Vanda as not directed to methods of treatment• Distinguished labeled MuSK from cDNA (Myriad) as not “a new

composition of matter that was not a natural product”• Distinguish from CellzDirect because “end result” of Athena’s claims

is just an observation or detection of a natural law, not an application of it

• Use of standard techniques (labeling; detecting) do not transform a claim into patentable subject matter under Step 2 of Mayo/Alice Test

64

Patent Ineligible


• CAFC has ruled inconsistently on the patent (in)eligibility of

diagnostic method claims

• Claims are directed to “a new multi-step” method.

• “[A] man-made reaction sequence employing new components

in a new combination to perform a new diagnostic procedure”

• Claim must be considered as a whole: “It is incorrect to excise from

the claims any steps that are performed by conventional

procedures.”

• Majority applied an incorrect analytical framework: “[M]y

colleagues hold that since the separate procedures are

conventional, it is irrelevant that the method as a whole is a new

method.”

• Concerned about the consequences of unpredictable patent

support on the development of future diagnostic methods

65

J. Newman’s Dissent


Patent Ineligible

Genetic Veterinary Sciences, Inc.

v. LABOklin GmbH & Co., KG (EDVA)

1. An in vitro method for genotyping a Labrador Retriever comprising: a)

Obtaining a biological sample from the Labrador Retriever; b) Genotyping

a SUV39H2 gene encoding the polypeptide of SEQ ID NO: 1 and c)

Detecting the presence of a replacement of a nucleotide T with a

nucleotide G at position 972 of SEQ ID NO:2.

• District court held that the method of claim 1 “begin and end” with a

discovery of a natural phenomenon: correlation of a point mutation

and a specific disease

• Distinct from Vanda because invention here not directed to a method

of applying the discovery or a method of treating Labradors

• Distinct from CellzDirect because not a new laboratory technique but

instead only an observation of the natural phenomena

• Applying Step 2: The specific steps are well-known and routine steps

of detection and genotyping

66

Patent Eligible

Pernix Ireland Pain DAC

v. Alvogen Malta Operations Ltd. (D. Del.)

Motion for re-argument of SJ decision denied: Case heard by Judge Bryson

sitting by designation

• Two types of method claims at issue: method of treating “non-adjustment”

of dose; and “PK-only” claims were dose is adjusted to achieve certain PK

parameters

• District court: “A claim to a method of treating an illness is typically more

than an expression of a natural law; if it were otherwise, pharmaceutical

patents would be hard to come by, as most methods of treatment using

pharmaceuticals consist simply of the administration of a drug that affects

the human body in a manner that is dictated by laws of nature.”

• “Adding limitations [PK parameters’] to a claim that satisfies section 101

does not convert the claim into one that is directed to unpatentable subject

matter.”

67

Patent Eligible

In re Biogen '755 Patent Litigation (DNJ)

1. A method for immunomodulation or treating a viral condition, a viral

disease, cancers or tumors comprising the step of administering . . . a

therapeutically effective amount of a composition comprising: a recombinant

polypeptide produced by a nonhuman host transformed by a recombinant

DNA molecule comprising a DNA sequence selected from [sequences for

expressing recombinant interferon-β]. . . said DNA sequence being

operatively linked to an expression control sequence in the recombinant

DNA molecule.

• Defs. argue: claim is (1) directed to natural phenomena because it uses the

same IFN polypetide found in nature to perform the same function in nature:

recombinant IFB does not change inquiry; (2) abstract idea of using a natural

product to perform its natural function (treating a viral disease)

• Biogen argues: method of treatment claims are consistently held patent-

eligible; claim does not use natural IFN, but recombinant; 3D protein

structure of natural and recombinant IFN are different

68

• District court noted that the 3D native and recombinant interferon-β

proteins are not the same (e.g., different glycosylation patterns).

• “As the Federal Circuit recognized in Vanda, method of treatment

claims (which apply natural relationships as opposed to being

‘directed to’ them) were identified by the Supreme Court as not

being implicated by its Mayo and Myriad decisions because they

‘confine their reach to particular applications.’”

• “Here, the claims at issue are method of treatment claims, not claims

to DNA or polypeptides. Moreover, as stated above, based on the

record evidence no reasonable jury could conclude that the

recombinant protein administered in the claimed method is identical

to the protein found in nature.”

69

Patent Eligible

In re Biogen '755 Patent Litigation (DNJ)

70

Ex Parte Nagy, 2018 WL 3855099 (PTAB July 30, 2018)

– method of assessing disease risk

Ex Parte Stroh et al, 2018 WL 7106369 (PTAB Dec. 31, 2018)

Ex Parte Stroh et al, 2018 WL 7131928 (PTAB Dec. 31, 2018)

- methods of predicting therapeutic efficacy

PTAB: Patent Ineligible, Post-Vanda

Patent Ineligible - Ex Parte Nagy

71

2. A method of assessing the risk of Alzheimer's disease

progression in a human subject suspected of having Alzheimer's

disease, which method comprises (i) obtaining lymphocytes . . . ;

(ii) inducing cell division in the lymphocytes . . . ; (iii) separating

the dividing lymphocytes of (ii) into two pools and treating one pool

of lymphocytes with rapamycin; (iv) assaying the level of protein of

at least one interleukin . . . ; (v) comparing the level of protein of

the at least one interleukin obtained in (iv) . . . ; (vi) repeating steps

(ii) - (v) using control lymphocytes taken from the age-matched

healthy subject with normal cognitive ability; and (vii) determining

that said human subject suspected of having Alzheimer's disease is

at increased risk of Alzheimer's disease progression when . . . .

PTAB held claims were similar to those held invalid in Mayo

Patent Ineligible - Ex Parte Stroh

17. An in vitro method for predicting the likelihood that a patient

suffering from KRAS wild type EGFR expressing metastatic

colorectal cancer (mCRC) will respond therapeutically to the

treatment with an anti-EGFR antibody, comprising: (a) measuring .

. . the expression level of EREG (b) exposing ex-vivo . . . to said

anti-EGFR antibody, (c) following exposure to said anti-EGFR

antibody, measuring . . . the expression level of EREG, and (d)

calculating the differences in expression levels measured in steps

(b) and (c) . . . and wherein said anti-EGFR antibody is administered

to said patient upon a finding in step (d) of an increased likelihood

that said patient responds therapeutically to the treatment with said

anti-EGFR antibody.

72

PTAB analogized these claims to claims held invalid in Mayo

• “an administered anti-EGFR antibody modulates EREG production through a natural process in the patient's biopsied tissue, in the same way that administering the thiopurine drug naturally elicits the 6-TG metabolite.”

• “the level of a biomarker -- 6-TG in Mayo and EREG in claim 17 -- is used similarly to tell the doctor about the effect of administering a drug to the patient.”

• “the steps ‘simply tell doctors to gather data from which they may draw an inference in light of the correlations,’ which in this case is whether or not to administer the anti-EGFR antibody.

PTAB notes that these claims are not method of treatment claims (the claims do not always lead to treatment) – therefore, Vanda does not apply.

73

Patent Ineligible - Ex Parte Stroh

PTAB: Patent Eligible, Post-Vanda

74

Ex Parte Schwartz et al, 2018 WL 3951533 (PTAB July 31,

2018) – method of modulating gene expression

Ex Parte Pierik et al, 2018 WL 4360570 (PTAB Aug. 28, 2018)

– method for testing nucleic acids on a support

Patent Eligible - Ex Parte Schwartz

75

21. A method [of] selectively modulating expression of a target

gene in the genome of a human cell determined to be in need

thereof, comprising: determining the presence of an encoded

antisense transcript overlapping a promoter of the target gene;

contacting the antisense transcript with an exogenous gapmer or

double-stranded agRNA; and detecting a resultant modulation of

expression of the target gene, . .

Examiner rejected the claims as directed to the abstract idea of

determining the presence of an encoded antisense transcript

Considering the claims as a whole, the PTAB held the claims are

directed not to a method of “determining the presence...” but to a

method of “selectively modulating expression of a target gene”

Patent Eligible - Ex Parte Pierik

1. A method for testing nucleic acids on a support, comprising the

steps of: (a) immobilizing one or more nucleic acids on a solid

support via crosslinking by heat or light or via chemical

immobilization, wherein each of the immobilized nucleic acids

includes a stretch of nucleotides of only one basetype; (b) providing

a labeled oligonucleotide complementary to the stretch of

nucleotides of only one basetype, wherein said labeled

oligonucleotide is capable of forming a complex with each of the

immobilized nucleic acids at the stretch of nucleotides of only one

basetype; and (c) determining a value indicative for the condition of

said nucleic acids via the amount of labeled oligonucleotide being

in complex with the immobilized nucleic acid.

76

PTAB analogized claims to those upheld as valid in Cellzdirect

• “Just as the method in Cellzdirect ‘is not simply an observation

or detection of the ability of hepatocytes to survive multiple

freeze-thaw cycles,’ the instant claims 1 and 15 are not simply a

method of observing but rather ‘recite processes to achieve a

desired outcome, e.g., methods of producing things.”

• “That is, the instant claims are entirely physical, not abstract.”

• Does not matter that claimed steps were already known in the

art

77

Patent Eligible - Ex Parte Pierik

Avoiding and Overcoming § 101

Rejections and Challenges

78

Percent of §101 Rejections

79

Source: bilskiblog.com, “Two Years After Alice: A Survey Of The Impact Of A “Minor Case” (Part 2)

”Jun. 20, 2016.

Avoiding/Overcoming a § 101 Rejection

General Tips

• Strategize for patent eligibility under section 101 based on USPTO guidance documents

• Anticipate eligibility rejections and plan a deliberate eligibility strategy to overcome

• Utilize a variety of invention settings (method/kit claims not visibly parallel to other claims)

• Draft and prosecute narrow claims first?• Limit to practical application

• Avoid elements that read on mental steps

80

Drafting or Amending Method Claims to

Avoid/Overcome a § 101 Rejection

• Recite a practical application and/or tangible result

• Recite at least one concrete/physical step

• If possible, recite a series of steps

• If possible, recite at least one non-routine element

• Choose a clear preamble, and continue with language consistent

with that preamble:

• A method of treatment . . .

• A method of preventing . . .

• A method of [achieving X tangible/measurable result] . . .

• A method of detecting X . . . comprising [physical detection step] . . .

• If claiming a method of diagnosis, include a non-routine

element or a treatment step

81

82

Drafting Claims to Avoid/Overcome

a § 101 Challenge:

Discrepancies between USPTO

practice and Case Law

Drafting Method Claims to

Avoid/Overcome a § 101 Challenge:

• A method of detecting Y, comprising obtaining a sample,

performing detection step X (e.g., sequencing or exposing

sample to an agent), and detecting target Y.

• A physical detection step is likely not enough for a method of

detection claim to survive a challenge during litigation.

• A method of detection claim should recite more than the

tracking of a natural phenomenon using known means.

83

Patent Eligible

USPTO (Example 29)PTAB (Ex Parte Terbrueggen)

Patent Ineligible

District Court (E.D. Va.) (Genetic Vet. Sci.)Fed. Cir. (Roche)

• Disclose practical applications (e.g., implementation beyond

“mental step” diagnosis, such as diagnosis + treatment)

• Disclose concrete examples of broadly-claimed methods (e.g.,

suitable technologies for carrying out the method)

• Disclose why recited elements (e.g., compositions, steps in a

method) are non-routine

• *Disclose why the invention is an improvement over the prior art

• *Disclose why one of skill in the art would not have reasonably

expected success in making the invention

84

Drafting the Specification to


* Though these elements are more appropriately § 103 considerations, they may also be helpful in overcoming a § 101 rejection.

• Argue that the claims recite physical/tangible elements (point to

support from specification)

• Argue that the claims recite non-routine elements

• *Argue that the invention is an improvement over the prior art

• *Argue that one of skill in the art would not have reasonably

expected success in making the invention

• *Argue that the prior art teaches away from the invention

85

Arguments during Prosecution to


* Though these elements are more appropriately § 103 considerations, they may also be helpful in overcoming a § 101 rejection.

Litigation Positions that may

Overcome a § 101 Challenge

• Emphasize practical application to analogize to Vanda

• Emphasize tangible outcome to analogize to CellzDirect

• Emphasize any specific/physical steps recited in the claim

• *Present evidence that an element or combination of

elements was non-routine or unlikely to succeed based on

prior art knowledge

• *Emphasize improvements over the prior art

86

* Though more appropriately a § 103 consideration, these positions have proven useful in overcoming § 101 challenges [CellzDirect, Idexx, Vanda (Dist Ct)].

Thank you.

87

Amanda K. Murphy, Ph.D. Finnegan, Henderson, Farabow, Garrett & Dunner, LLP901 New York Avenue, NWWashington, DC [email protected]

Steven P. O’Connor, Ph.D.Finnegan, Henderson, Farabow, Garrett & Dunner, LLPTwo Freedom Square11955 Freedom Dr.Reston, VA [email protected]

Sara A. Leiman, Ph.D. Finnegan, Henderson, Farabow, Garrett & Dunner, LLPTwo Seaport LaneBoston, MA [email protected]

Sanya SukduangFinnegan, Henderson, Farabow, Garrett & Dunner, LLP901 New York Avenue, NWWashington, DC [email protected]

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