CSL Limited

Patent Trials and Appeals Board

Dec 28, 2020

2020002030 (P.T.A.B. Dec. 28, 2020)

UNITED STATES PATENT AND TRADEMARK OFFICE
UNITED STATES DEPARTMENT OF COMMERCE
United States Patent and Trademark Office
Address: COMMISSIONER FOR PATENTS
P.O. Box 1450
Alexandria, Virginia 22313-1450
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
15/054,358 02/26/2016 Craig RAYNER 06478.1593-01000 1349
22852 7590 12/28/2020
FINNEGAN, HENDERSON, FARABOW, GARRETT & DUNNER
LLP
901 NEW YORK AVENUE, NW
WASHINGTON, DC 20001-4413
EXAMINER
DABKOWSKI, ERINNE R
ART UNIT PAPER NUMBER
1654
NOTIFICATION DATE DELIVERY MODE
12/28/2020 ELECTRONIC
Please find below and/or attached an Office communication concerning this application or proceeding.
The time period for reply, if any, is set in the attached communication.
Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the
following e-mail address(es):
regional-desk@finnegan.com
PTOL-90A (Rev. 04/07)

UNITED STATES PATENT AND TRADEMARK OFFICE
____________

BEFORE THE PATENT TRIAL AND APPEAL BOARD
____________

Ex parte CRAIG RAYNER
____________

Appeal 2020-002030
Application 15/054,358
Technology Center 1600
____________

Before JEFFREY N. FREDMAN, DEBORAH KATZ, and JOHN G. NEW,
Administrative Patent Judges.

FREDMAN, Administrative Patent Judge.

DECISION ON APPEAL
This is an appeal1,2 under 35 U.S.C. § 134(a) involving claims to
administering fixed dosages of apolipoprotein formulations. The Examiner
rejected the claims as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We affirm.

1 We use the word “Appellant” to refer to “applicant” as defined in 37
C.F.R. § 1.42. Appellant identifies the Real Party in Interest as CSL
LIMITED (see Appeal Br. 4).
2 We have considered and herein refer to the Specification of Feb. 26, 2016
(“Spec.”); Final Office Action of July 12, 2018 (“Final Act.”); Appeal Brief
of Aug. 13, 2019 (“Appeal Br.”); Examiner’s Answer of Nov. 21, 2019
(“Ans.”); and Reply Brief of Jan. 16, 2020 (“Reply Br.”).
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Statement of the Case
Background
“[C]linical administration of apolipoprotein formulations such as in
the form of reconstituted [high-density lipoproteins (“HDL”)] (rHDL)
formulations have been shown to confer beneficial effects to
hypercholesterolemic patients suffering from recent acute coronary
syndromes (ACS)” (Spec. 1:19–22). “Dosages of apolipoprotein
formulations, such as rHDL formulations, are typically calculated according
to the body weight of the patient or individual to whom the formulation is
administered” (id. at 1:23–25). “[T]he expectation is that body weight based
dosing of the apolipoprotein formulation would result in each patient
receiving the same exposure to the apolipoprotein with minimal variation
between patients of the same or different body weights” (id. at 1:27–30).
The Specification explains that “[t]he invention at least partly arises from the
unexpected discovery that a fixed dosing regime[n] for apolipoprotein
formulations (e.g. rHDL) independent of patient body weight has less impact
on apoA-1 exposure over a range of patient body weights than that imposed
by body weight-adjusted dosing” (id. at 5:27–30).
The Claims
Claims 1, 4, 7, 8, 10, 12–17, 40, 44, and 45 are on appeal.3
Independent claim 1 is representative and reads as follows:
1. A method of therapeutically treating a disease, disorder, or
condition in a human in need thereof comprising
administering to the human a fixed dosage of an
apolipoprotein formulation in order to therapeutically treat the
disease, disorder, or condition in the human,

3 Status of other claims (withdrawn, cancelled, etc.)
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wherein the disease, disorder, or condition is selected
from the group consisting of cardiovascular disease,
hypercholesterolemia, and hypocholesterolemia,
wherein the apolipoprotein is Apolipoprotein A1 (Apo-
A1),
wherein the human has a body weight of 60 kg to 140 kg,
wherein the fixed dosage comprises an amount of
apolipoprotein in a range of 5 g to 7 g, and
wherein the apolipoprotein formulation dosage is not
calculated, determined, or selected according to the particular
body weight of the human.

The Rejections
A. The Examiner rejected claims 1, 4, 7, 8, 10, 12–15, 44 and 45 under
35 U.S.C. § 103(a) as obvious over Eriksson,4 Patel,5 and Drew6 (Ans. 3–5).
B. The Examiner rejected claims 1, 4, 7, 8, 10, 12–16, 44 and 45 under
35 U.S.C. § 103(a) as obvious over Eriksson, Patel, Drew, and Dasseux7
(Ans. 5–6).
C. The Examiner rejected claims 1, 4, 7, 8, 10, 12–17, 40, 44 and 45
under 35 U.S.C. § 103(a) as obvious over Eriksson, Patel, Drew, Dasseux,
and Lerch8 (Ans. 6–8).

4 Eriksson, et al., Stimulation of Fecal Steroid Excretion After Infusion of
Recombinant Proapolipoprotein A-I - Potential Reverse Cholesterol
Transport in Humans, 100 Circulation 594–598 (1999).
5 Patel et al., Reconstituted High-Density Lipoprotein Increases Plasma
High-Density Lipoprotein Anti-Inflammatory Properties and Cholesterol
Efflux Capacity in Patients With Type 2 Diabetes, 53 J. Am. College
Cardiology 962–971 (2009).
6 Drew et al., High-Density Lipoprotein Modulates Glucose Metabolism in
Patients With Type 2 Diabetes Mellitus, 119 Circulation 2103–2111 (2009).
7 Dasseux, WO 2006/100567 A1, published Sept. 28, 2006.
8 Lerch et al., US 5,652,339, issued July 29, 1997.
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A. 35 U.S.C. § 103 over Eriksson, Patel, and Drew
The Examiner finds Eriksson teaches a method of administering a
fixed dosage of 4 g apolipoprotein-A1 to hypercholesterolemia patients
weighing 80 to 97 kg (Ans. 3). The Examiner finds Patel and Drew teach
administering 80 mg/kg Apo-A1 to patients having a body weight of
107.8±28 kg to increase high-density lipoproteins (“HDL”) and protect
against atherosclerosis (Id. at 4). The Examiner finds that the dosage
amount of Apo-A1 is a result effective variable, and finds that a person of
ordinary skill in the art would have been motivated to optimize Eriksson’s
fixed dosage of Apo-A1 to include the range of 5 g to 7 g (id. at 4–5).
The issue with respect to this rejection is: Does a preponderance of
the evidence of record support the Examiner’s conclusion that the
combination of Eriksson, Patel, and Drew renders the claims obvious?
Findings of Fact (“FF”)
1. Eriksson teaches a method for increasing body cholesterol
excretion by administering recombinant proapo-AI9 liposome complexes
(Eriksson 597).
2. Eriksson teaches administering 200 mL of recombinant human
proapoA-I soybean phosphatidylcholine liposomes containing 4 g of Apo-AI
by intravenous infusion (Eriksson 595).
3. Eriksson teaches treating four patients, individually weighing
80, 85, 87, and 97 kg (Eriksson 595).
4. Eriksson teaches that all four patients had phenotypical
heterozygous familial hypercholesterolemia and two patients had coronary
heart disease (Eriksson 595).

9 The prior art references refer to Apo-A1 as Apo-AI.
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5. Eriksson teaches “[t]he patients were given a standardized,
natural-type diet adjusted to keep their weight and cholesterol and fat intake
stable” (Eriksson 595).
6. Eriksson teaches that “during >1 week after the infusion, a
mean of ≈ 500 mg/d excess cholesterol was being removed” (Eriksson 596).
7. Patel teaches “rHDL infusions have significant, potentially
atheroprotective effects in individuals with diabetes, including suppression
of inflammation and enhancement of cholesterol efflux” (Patel 962).
8. Patel teaches administering 80 mg/kg rHDL consisting of Apo-
AI isolated from human plasma, phosphatidyl choline from soy bean, and
sodium cholate (Patel 963).
9. Patel teaches administering Apo-AI to 13 patients weighing
107.8±7.8 kg (Patel 963).
10. Drew teaches administering “rHDL reduced plasma glucose in
patients with type 2 diabetes mellitus by increasing plasma insulin and
activating AMP-activated protein kinase in skeletal muscle. These findings
suggest a role for HDL-raising therapies beyond atherosclerosis to address
type 2 diabetes mellitus” (Drew 2103).
11. Drew teaches administering 80 mg/kg rHDL consisting “of
apolipoprotein AI (apoAI) isolated from human plasma and
phosphatidylcholine (PC) from soy bean . . . combined in the presence of
sodium cholate” (Drew 2104, Supplemental Material).
12. Drew teaches administering Apo-AI to 13 patients having a
body weight of 107.8±28 kg (Drew 2104).
13. Drew teaches “rHDL infusion increased plasma HDL by
l.33±0.43-fold (Figure 1A) and plasma apoAI protein (Figure 1B) by
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2.41±0.1.5-fold (P<0.001 for both) compared with placebo at the end of the
4-hour infusion” (Drew 2105, Fig. 1).
Principles of Law
“In determining whether the subject matter of a patent claim is
obvious, neither the particular motivation nor the avowed purpose of the
patentee controls. What matters is the objective reach of the claim. If the
claim extends to what is obvious, it is invalid under § 103.” KSR Int’l Co. v.
Teleflex Inc., 550 U.S. 398, 419 (2007).
Analysis
We adopt the Examiner’s findings of fact and conclusion of law (see
Ans. 3–8, FF 1–13) and agree that the combination of Eriksson, Patel, and
Drew renders the claims obvious. We address Appellant’s arguments below.
Appellant contends the Examiner misinterprets “fixed dosage” as a
“set amount of apolipoprotein” regardless of whether that amount was
administering using a weight-based dosing regimen (Appeal Br. 6–7).
Appellant contends that the Specification “describes the term ‘fixed dosage’
as a dosage that ‘is not calculated, determined or selected according to the
particular body weight of the human, such as would typically occur with
weight-adjusted dosing’” (id. at 7, citing Spec. 9:5–8). Appellant contends
that “[b]y relying on Patel and Drew’s weight-based dosing approach to
guide the selection of a dosage for Eriksson’s subjects, the Examiner is
selecting a gram amount of Apo-A1 based on the body weight of a subject of
Eriksson, which is expressly contrary to the claimed method” (id. at 8)
(emphasis omitted).
We do not find this argument persuasive because Appellant does not
address the Examiner’s rejection. As explained by the Examiner, “Eriksson
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teaches administering 4 grams to a variety of weight patients and the
teachings of Patel and Drew were used as motivation to optimize[]/increase
the dosage of Eriksson for improved therapeutic efficacy” (Ans. 11).
Specifically, the Examiner finds that Patel and Drew teach increased doses
including 6.96/7.0 grams (id.). We do not agree with Appellant that
optimizing Eriksson’s fixed doses to improve therapeutic efficacy changes
the fixed dose to a weight-adjusted dose. Rather, a person of ordinary skill
in the art would have considered the known prior art doses when optimizing
Eriksson’s fixed dose. “A person of ordinary skill is also a person of
ordinary creativity, not an automaton.” KSR, 550 U.S. at 421. The resulting
optimized fixed dose, between 4 g and 7 g, would accordingly be
administered without being calculated, determined or selected according to
the particular body weight of the human as claimed.
Appellant contends that a person of ordinary skill in the art would
have concluded that Eriksson’s dosing regimen is a weight-based dosage
amount rather than fixed dosage (Reply Br. 5, citing Tortorici Decl. ¶ 18)
(emphasis omitted). Dr. Tortorici states that Eriksson describes giving its
subjects a standardized diet “in part to ‘keep their weight . . . stable’”
(Tortorici Decl. ¶ 18). Dr. Tortorici states that “[k]eeping body weight
stable during the duration of the study would be unnecessary if it were
understood that the same dosage would be effective for a wide range of body
weights” (id.). Dr. Tortorici states that a person of ordinary skill in the art
would have concluded that “Eriksson’s dosage was suitable only for persons
having a body weight of about 90 kg (i.e., a weight-based dosage of about 45
mg/kg)” (id.). Appellant contends that the Examiner improperly ignored Dr.
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Tortorici’s declaration and disregards the declaration as “a fair reading of
Eriksson by a person of ordinary skill in the art” (Reply Br. 6.)
We are not persuaded by Appellant’s argument because Dr.
Tortorici’s broad conclusory statements are not supported by corroborating
evidence. See Velander v. Garner, 348 F.3d 1359, 1371 (Fed. Cir. 2003).
Eriksson teaches giving the patients a standardized “diet adjusted to keep
their weight and cholesterol and fat intake stable” (FF5, emphasis added).
Accordingly, there are numerous reasons for providing a standardized diet to
hypercholesterolemic patients in a clinical study that measures cholesterol
excretion, that are unrelated to weight-based dosing (see also Ans. 14
(“Weight gain and changes of diets can have effects on the end outcome
measurements including cholesterol and cholesterol efflux. One cannot
assume that this is Eriksson’s way of saying the dosage is based on body
weight”)). In contrast, Erikson does not limit the study to individuals with
identical weight, but rather includes weights ranging from 80 to 97 kg (FF
3). Dr. Tortorici cites no specific evidence of record to support the
statements made in his conclusion. Because Dr. Tortorici has not cited any
specific evidence that provides a factual basis for his conclusions, we give
his testimony little weight as evidence. See In re Am. Acad. Of Sci. Tech
Ctr., 367 F.3d 1359, 1368 (Fed. Cir. 2004) (“the Board is entitled to weigh
the declarations and conclude that the lack of factual corroboration warrants
discounting the opinions expressed in the declarations”).
Appellant also contends that the Examiner fails to provide a
motivation to administer a fixed Apo-A1 dosage of 5 g to 7 g, and the fails
to establish a reasonable expectation of success based on the cited references
(Appeal Br. 11). Appellant contends that “the Examiner’s position fails to
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consider Dr. Tortorici’s conclusion that a person of skill in the art reading
Eriksson would not have predicted success in administering any fixed
dosage of apolipoprotein to persons having the recited range of body
weights” (id. at 12). Appellant further contends that “Patel and Drew
describe using vastly different amounts of Apo-A 1 among their respective
subjects,” as weight-based dosing results in a “large discrepancy in the
amount of apolipoprotein administered across a range of body weights” (id.
at 13). Accordingly, Appellant contends that “[c]ombined with Eriksson’s
focus on a narrow body weight range to maintain a consistent administered
amount of apolipoprotein per subject, Patel and Drew instead highlight the
skilled artisan’s inability to predict success in using any fixed dosage across
the recited weight range of 60 kg to 140 kg” (id. at 13).
We find Appellant’s arguments unpersuasive as to the Examiner’s
reason modify the references and the reasonable expectation of success in
the modification. First, as to the reason to modify the references, Eriksson
teaches administering a fixed dose amount to humans having a range of
body weights within the claimed weight range (FF 2, 3). The Examiner
finds that the fixed dose amount is a result effective variable, and that a
person of ordinary skill in the art would have optimized the fixed dose
amount in view the larger existing doses known in the prior art (Ans. 10).
“[T]he discovery of an optimum value of a variable in a known process is
normally obvious.” In re Antonie, 559 F.2d 618, 620 (CCPA 1977).
Exceptions to this rule include (1) the results of optimizing a variable were
unexpectedly good and (2) the parameter optimized was not recognized in
the prior art as one that would affect the results (id.). Appellant has not
presented evidence that the results of optimizing the fixed dose amount were
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unexpectedly good or that the dose amount of Apo-A1 was not recognized in
the prior art as one that would affect the results. Accordingly, we are not
persuaded that the Examiner erred in finding a reason to modify Eriksson’s
method.
Second, as to the reasonable expectation of success, Appellant relies
on Dr. Tortorici’s Declaration to argue that a person of ordinary skill in the
art would not “reasonably have expected success” in administering “a single
fixed dosage to persons having body weights across the range of 60 kg to
140 kg” (Appeal Br. 11–12, citing Tortorici Decl. ¶ 18). We find
Appellant’s argument unpersuasive because Dr. Tortorici’s statement does
not address the obviousness rejection as presented. Eriksson teaches
administering a fixed dose amount to humans in a weight range that is
encompassed by the claimed range (FF 2, 3). Patel and Drew each teach
administering larger dose amounts to humans in a weight range that overlaps
Eriksson’s range and the claimed range (FF 8, 9, 11, 12). The Examiner
finds a reasonable expectation of success in administering a larger fixed dose
to humans within the weight range that overlaps Eriksson, Patent and Drew,
and the claimed range (see Ans. 17). Appellant does not rebut this finding
with evidence of unexpected results. See In re Geisler, 116 F.3d 1465, 1469
(Fed. Cir. 1997) ([A] prima facie case of obviousness based on overlapping
ranges “can be rebutted if the applicant (1) can establish ‘the existence of
unexpected properties in the range claimed’ or (2) can show ‘that the art in
any material respect taught away’ from the claimed invention”).
As to teaching away, we give little weight to Dr. Torotrici’s
statements that Patel and Drew teach away from fixed dose amounts because
the statements lack corroborating evidence (see above). The absence of
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corroborating evidence may be directly contrasted with the evidence relating
to enablement in paragraphs 5–14 of the Tortorici Declaration, which the
Examiner found persuasive (see Final Act. of July 12, 2018, at 3). Appellant
does not identify any specific teachings in Patel or Drew that discourage the
use of fixed dose amounts. See In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir.
2004) (“The prior art’s mere disclosure of more than one alternative does not
constitute a teaching away from any of these alternatives because such
disclosure does not criticize, discredit, or otherwise discourage the solution
claimed.”) Because Appellant does not rebut the Examiner’s finding of a
reasonable expectation of success, we are not persuaded that the Examiner
erred.
Conclusion of Law
A preponderance of the evidence of record support the Examiner’s
conclusion that Eriksson, Patel, and Drew render the claims obvious.

B and C. 35 U.S.C. § 103 over Eriksson, Patel, Drew, Dasseux,
and Lerch
Appellant does not substantively argue these obviousness rejections,
instead relaying on their arguments to overcome Eriksson, Patel, and Drew
(Appeal Br. 14–17). The Examiner provides sound fact-based reasoning for
combining the references (see Ans. 5–8). Having affirmed the obviousness
rejection of claim 1 over Eriksson, Patel, and Drew for the reasons given
above, we also find that the further combinations render the claims obvious
for the reasons given by the Examiner.

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DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
1, 4, 7, 8, 10,
12–15, 44, 45
103 Eriksson, Patel,
Drew
1, 4, 7, 8, 10,
12–15, 44, 45

1, 4, 7, 8, 10,
12–16, 44, 45
103 Eriksson, Patel,
Drew, Dasseux
1, 4, 7, 8, 10,
12–16, 44, 45

1, 4, 7, 8, 10,
12–17, 40,
44, 45
103 Eriksson, Patel,
Drew, Dasseux,
Lerch
1, 4, 7, 8, 10,
12–17, 40, 44,
45

Overall
Outcome
1, 4, 7, 8, 10,
12–17, 40, 44,
45

No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

AFFIRMED