YEH, James Shue-Min

Patent Trials and Appeals Board

Dec 13, 2021

2021002061 (P.T.A.B. Dec. 13, 2021)

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.
14/654,650 06/22/2015 James Shue-Min YEH 1380-6PUS
(P528775US-PCT)
5448
31292 7590 12/13/2021
CHRISTOPHER & WEISBERG, P.A.
1232 N. University Drive
Plantation, FL 33322
EXAMINER
PERREIRA, MELISSA JEAN
ART UNIT PAPER NUMBER
1618
NOTIFICATION DATE DELIVERY MODE
12/13/2021 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):
docketing@cpaglobal.com
ptomail@cwiplaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte JAMES SHUE-MIN YEH
Appeal 2021-002061
Application 14/654,650
Technology Center 1600
BEFORE ERIC B. GRIMES, JEFFREY N. FREDMAN, and JOHN E.
SCHNEIDER, Administrative Patent Judges.
SCHNEIDER, Administrative Patent Judge.
DECISION ON APPEAL
STATEMENT OF THE CASE
Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the
Examiner’s decision to reject claims 1−4, 6−23, 25, 28−29, 32−36, 38−50,
52, 55−56, 59−64, and 70.2 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(a). Appellant identifies the real party in interest as the inventor, James
Shue-Min Yeh. Appeal Br. 3.
2 Claims 65–69 and 71–75 are pending in the application but have been
withdrawn from consideration. Final Act. 1.
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CLAIMED SUBJECT MATTER
The claims are directed to ultrasound molecular imaging. Ultrasound
molecular imaging “facilitates imaging of a given molecular moiety/moieties
of interest (expressions) by way of targeting microbubbles, which comprise
targeting ligands (molecular binding elements) on the particle shell.” Spec.
1. The invention is directed to microparticles suitable for use in ultrasound
molecular imaging. Id. at 2. Claim 1, reproduced below, is illustrative of the
claimed subject matter:
1. A microparticle composition suitable for molecular imaging,
the composition comprising microparticles, wherein the
microparticles comprise:
a core microparticle structure having a central area and a
shell, and wherein the core microparticle structure comprises:
(i) a C18-24 saturated phosphatidylcholine lipid in a
molar ratio of 72 to 78;
(ii) a C18-24 saturated phosphatidylethanolamine lipid
comprising at least one maleimide moiety in a molar ratio of 7
to 12 and a polyethylene glycol chain with a molecular weight
of at least 500; and
(iii) an alkoxylated fatty acid in a molar ratio of 12 to 18,
the alkoxylated fatty acid being a C18-24 saturated
polyethylene glycol fatty acid ester.
REFERENCES
The prior art relied upon by the Examiner is:
Name Reference Date
Unger US 6,088,613 July 11, 2000
Rychak US 2012/0244078 Sept. 17, 2012

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Application 14/654,650
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REJECTION
The Examiner has rejected claims 1−4, 6−23, 25, 28−29, 32−36,
38−50, 52, 55−56, 59−64, and 70 under 35 U.S.C. § 103 as unpatentable
over Rychak in view of Unger.
OPINION
Issue
The issue before us is whether a preponderance of the evidence
supports the Examiner’s conclusion that the subject matter of claims 1−4,
6−23, 25, 28−29, 32−36, 38−50, 52, 55−56, 59−64, and 70 would have been
obvious to one of ordinary skill in the art at the time the invention was made
over Rychak combined with Under.
The Examiner finds Rychak teaches “a gas-encapsulated injectable
microbubble bearing a targeting ligand specific for a molecular target on its
surface.” Ans. 3. The Examiner finds the microbubble of Rychak comprises
a shell comprising a first surfactant which may be phosphatidyl choline
which has a mole ratio of 5–90% relative to the other shell components Id. at
4. The Examiner finds that shell of Rychak also comprises a second
surfactant which may be disteroylphosphatidylethanolamine-polyethylene
glycol-2-pyridyl sulfide (“DSPE-PEG(2000)-PDP”) which is present in the
shell in a moles/moles ratio of 0.1-99%, relative to other shell components.
Id. The Examiner finds that the microbubble comprises a targeting ligand
immobilized in the shell. Id. at 5. The Examiner finds the targeting ligand of
Rychak is present in the shell in a mole ratio of from 0.1 to 5% relative to
the other components of the shell. Id. The Examiner find the ligand can be a
peptide, a protein or an antibody. Id.
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The Examiner finds Rychak does not teach the specific mole ratios
recited in the claims but finds these mole ratios are suggested by Unger. Id.
at 6–7.
The Examiner concludes:
At the time of the invention it would have been obvious
to one ordinarily skilled in the art to vary and/or optimize the
amount of the lipids, labelling moiety, molecular binding
element etc., provided in the composition, according to the
guidance provided by Rychak, to provide a composition having
the desired properties such as the desired ratios as Rychak
teaches of that the first surfactant is present in the shell in a
moles/moles ratio of 5-90%, relative to other shell components,
the second surfactant is present in the shell in a moles/moles
ratio of 0.1-99%, relative to other shell components, the
targeting ligand is present in the shell in a moles/moles ratio of
0.1-5%, relative to other shell components and the optically
active probe is present in the shell in a moles/moles ratio of 0.1-
10%, relative to other shell components.
Also, Unger teaches of gas filled microbubbles
comprising 77.5 mole percent DPPC, 12.5 mole percent DPPA
and 10 mole percent DPPE/PEG5000 or 82/10/8 ratio of mole
percentages. Therefore, it would have been predictable to look
to Unger for guidance for the mole% ratios of the microbubble
lipid constituents. For example, one would examine the
phosphatidylcholine in a range between about 77.5 to 82
mole%, and phosphatidylethanolamine lipid in a range between
about 8-10 mole%.
It is noted that “[W]here the general conditions of a claim
are disclosed in the prior art, it is not inventive to discover the
optimum or workable ranges by routine experimentation.” In re
Aller, 220 F.2d 454,456, 105 USPQ 233, 235 (CCPA 1955).

Id. at 7–8.
Appellant contends that Unger only discloses hypothetical examples
and uses a negatively charged lipid which is not an element of the present
claims. Appeal Br. 5–6. Appellant argues the examples of Rychak do not
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5
teach the claimed invention as the length of the phosphatidylcholine lipid in
example 2 is not disclosed and Example 1 does not disclose the third
component of the claims. Id. at 7. Appellant also contends that Rychak does
not teach the specific mole ranges recited in the claims. Id.
Appellant contends that the microparticles of Rychak and Unger are
designed for different purposes and that one skilled in the art would not
combine the teachings of the references. Id. at 7–9. Appellant contends that
the microparticles of Rychak are designed to be fragile so that they can be
easily degraded by acoustic action, whereas the microparticle of Unger are
designed to be stable. Id. Appellant contends that combining the teachings of
the references would result in a particle that is unsatisfactory for its intended
purpose. Id.
Appellant also contends that Unger incorporates a charged lipid into
the shell to increase vesicle stability and that this would be contrary to the
purpose of Rychak which is to have a vesicle that is easily disrupted. Id. at
9–10. Appellant contends that there is no motivation to combine the
teachings of the references. Id.
Appellant contends that one skilled in the art would not apply the
mole ratios taught in Unger to the composition of Rychak. Id. at 11–13 and
15–18. Appellant contends that Unger teaches charged lipids that comprise
fewer carbon atoms and that this would lead one skilled in the art way from
using the mole ratios of Unger in Rychak. Id.
Appellant contends that Unger fails to teach binding the negatively
charged lipid to a PEG group. Id. at 13–14.
Appellant contends that Rychak does not teach a C18-24
phosphatidylcholine lipid as Example 2, which teaches a microbubble
comprising 40 mg of phosphatidylcholine, 20 mg polyoxyethylene 40
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stearate, and 5 mg of PDP-PEG(2000)disteroylphosphatidylethanolamine
does not disclose the chain length of the phosphatidylcholine. Id. at 19.
Appellant contends that the rejection is based on the improper use of
hindsight. Id. at 20. Appellant contends that only through the use of
hindsight would one have been lead to the claimed composition. Id.
Finally, Appellant contends that the claimed invention possesses
unexpected advantages not taught or suggested by Rychak or Unger. Id. at
21–25.
Legal Principles
[T]he examiner bears the initial burden, on review of the
prior art or on any other ground, of presenting a prima facie
case of unpatentability. If that burden is met, the burden of
coming forward with evidence or argument shifts to the
applicant. After evidence or argument is submitted by the
applicant in response, patentability is determined on the totality
of the record, by a preponderance of evidence with due
consideration to persuasiveness of argument.

In re Oetiker, 977 F.2d 1443, 1445 (Fed. Cir. 1992).
The test of obviousness is “whether the teachings of the prior art,
taken as a whole, would have made obvious the claimed invention.” In re
Gorman, 933 F.2d 982, 986 (Fed. Cir. 1991).
“Non-obviousness cannot be established by attacking references
individually where the rejection is based upon the teachings of a
combination of references. . . . [The reference] must be read, not in isolation,
but for what it fairly teaches in combination with the prior art as a whole.” In
re Merck & Co., 800 F.2d 1091, 1097 (Fed. Cir. 1986).
“[W]here there is a range disclosed in the prior art, and the claimed
invention falls within that range, there is a presumption of obviousness. But
the presumption will be rebutted if it can be shown: (1) That the prior art
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taught away from the claimed invention, In re Geisler, 116 F.3d 1465, 1471
(Fed. Cir. 1997); or (2) that there are new and unexpected results relative to
the prior art, In re Woodruff, 919 F.2d 1575, 1578 (Fed. Cir. 1990).” Iron
Grip Barbell Co. v. USA Sports, Inc., 392 F.3d 1317, 1322 (Fed. Cir. 2004).
Analysis
We adopt the Examiner’s findings of fact, reasoning on scope and
content of the prior art, and conclusions set out in the Final Action and
Answer regarding this rejection. We find the Examiner has established a
prima facie showing that the subject matter of the claims would have been
obvious over Rychak combined with Unger to a person of ordinary skill in
the art at the time the invention was made. Appellant has not produced
evidence showing, or persuasively argued, that the Examiner’s
determinations on obviousness are incorrect. Only those arguments made by
Appellant in the Briefs have been considered in this Decision. Arguments
not presented in the Briefs are waived. See 37 C.F.R. § 41.37(c)(1)(iv). We
have identified claim 1 as representative; therefore, all claims fall with claim
1. We address Appellant’s arguments below.
Appellant contends that Unger does not contain any data to show that
any of the lipids disclosed therein would actually work as described and that
Unger’s examples are prophetic. Appeal Br. 4–6. Appellant contends that
this supports its contention that the rejection is in error. Id.
We are not persuaded by this argument. Unger was relied on only for
the teaching of the relative mole ratios of the different components recited in
the claims. See Ans. 6–7. Appellant has offered no evidence to show why
one skilled in the art would not accept this teaching at face value. “[A]ll
disclosures of the prior art . . . must be considered.” In re Lamberti, 545
F.2d 747, 750 (CCPA1976). In addition, as discussed below, the recited
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ranges fall within the ranges taught by Rychak, supporting a prima facie case
of obviousness.
Appellant contends that Rychak fails to teach the claimed composition
in that Example 2 does not disclose the length of the phosphatidylcholine
used. Appeal Br. 7. Appellant contends that while Example 1 of Rychak
discloses a C18 phosphatidylcholine, the composition recited in that
example is missing the third element of the claims. Id. This argument is
unpersuasive.
Rychak teaches that the first lipid can be a phospholipid having an
acyl chain of from 10 to 28 carbon atoms and lists phosphatidylcholine as an
example. Rychak, claims 1–5. As Appellant points out, Example 1 of
Rychak teaches the use of a C18 phosphatidylcholine. Id. ¶ 49. We find that,
given the teachings of Rychak as a whole, it would have been obvious to one
skilled in the art reading Rychak to use a C18 phosphatidylcholine to make
the microbubbles of Rychak.
Appellant contends that Rychak does not teach or suggest the ranges
of mole ratios recited in the claims. Appeal Br. 7. Appellant contends that
the ranges recited in Rychak are so broad “as to encompass practically any
quantity of these components, and consequently provide no teaching of an
actual amount or moles/moles ratio of these components that can be used in
a microbubble composition.” Again, this argument is unpersuasive.
Rychak teaches that the first surfactant is present in the shell in a
moles/moles ratio of from 5–90% relative to the other components, the
second lipid is present in a moles/moles ration of from 0.1–99%, relative to
the other shell components, and the targeting ligand is present in the shell in
a moles/moles ratio of from 0.1–5%. Rychak Claims 15–18. The ranges
recited in Appellant’s claims fall within these recited ranges rendering the
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ranges obvious absent evidence that the references teach away from the
claimed ranges or there is evidence of unexpected results. Iron Grip Barbell,
392 F.3d at 1322. Appellant does not point to nor do we discern any
teaching away from the recited ranges in the references. See Appeal Br. 7. In
addition, as discussed more fully below, Appellant has not presented any
persuasive evidence of unexpected results.
Appellant contends that one skilled in the art would not combine the
teachings of Unger and Rychak as they are directed to two different
objectives and that combining the references would produce a microbubble
that is unsatisfactory for its intended purpose. Appeal Br. 7–9. Appellant
contends that Rychak is directed to producing a fragile microbubble that can
be easily ruptured. Id. Appellant contends that Unger is directed to a stable
microbubble that is not easily ruptured. Id. Appellant contends that
incorporating the teachings of Unger into Rychak would result in a
microbubble that would be unsuitable for Rychak’s intended purpose. Id.
We find this argument unpersuasive. Both Rychak and Unger teach
the preparation of microparticles for use in imaging. Rychak ¶ 14; Unger
Abst. Both Unger and Rychak teach that the microparticles can be ruptured
using ultrasound once the microparticles are in the target region. Unger col.
5, ll. 4–6; Rychak ¶ 22. Rychak teaches that the microparticles are allowed
to accumulate in a tumor of up to 30 minutes, then observed using
ultrasound, and then disrupted by a more intense ultrasound signal to release
a therapeutic agent. Rychak ¶ 75. Given that the microparticles of Unger and
Rychak are both used for the same purposes and may possess similar
degrees of stability we find that incorporation of the teachings of Unger into
Rychak would not render the microparticles unsuitable for the purpose of
Rychak.
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Appellant contends that one skilled in the art would not be motivated
to use the mole ratio of Unger in the microparticles of Rychak as Unger uses
a negatively charged lipid which would produce different properties in the
microparticle. Appeal Br. 11–14. We are not persuaded by this argument. As
discussed above, the mole ratios recited in the claims fall within the ratios
taught by Rychak rendering those ranges obvious.
Appellant contends that Unger does not teach or suggest a negatively
charged lipid covalently bound to a PEG group, and thus “a skilled person
would not consider combining the teachings of Rychak and Unger in order
to arrive at component (iii) of pending claims 1 and 34.” Appeal Br. 14. This
argument is unpersuasive. While Unger may not teach a negatively charged
lipid bonded to PEG, Rychak teaches the C18 PEG bonded element of claim
1. Rychak ¶¶ 49 and 51, claim 6.
Appellant contends that the Examiner engaged in the impermissible
use of hindsight in making the rejection. Appeal Br. 20. Appellant contends
that one skilled in the art would need to make several selections to arrive at
the claimed invention and that the references provide no guidance as to how
to arrive at the claimed invention. Id. Appellant contends that the specific
mole ratios recited in the claims results in the specific in vivo functions that
one skilled in the art would only achieve those results starting with Rychak
through the use of hindsight. Id.
We have considered Appellant’s argument and the evidence of record
and are not convinced that the rejection is based on the improper use of
hindsight.
“Any judgment on obviousness is in a sense necessarily a
reconstruction based upon hindsight reasoning, but so long as it takes into
account only knowledge which was within the level of ordinary skill at the
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time the claimed invention was made and does not include knowledge
gleaned only from applicant’s disclosure, such a reconstruction is proper.”
In re McLaughlin, 443 F.2d 1392, 1395 (CCPA 1971).
As discussed above, the mole ratios recited in the claims fall within
the ratios taught by Rychak. Finding the optimum ratios would be within the
skill of one skilled in the art and does not render the claims patentable.
“[W]here the general conditions of a claim are disclosed in the prior art, it is
not inventive to discover the optimum or workable ranges by routine
experimentation.” In re Aller, 220 F.2d 454, 456 (CCPA 1955). We discern
nothing in the rejection that is gleaned solely from Appellant’s disclosure.
Appellant contend that the present invention has advantages not
taught by the references and that are unexpected. Appeal Br. 21–25. We are
not persuaded that the evidence of record demonstrates unexpected results
sufficient to demonstrate patentability.
While the Specification reports results that appear to show certain
advantages of the present invention, the comparisons reported in the
Specification do not compare the invention against the closest prior art,
Rychak. “To be particularly probative, evidence of unexpected results must
establish that there is a difference between the results obtained and those of
the closest prior art, and that the difference would not have been expected by
one of ordinary skill in the art at the time of the invention.” Bristol-Myers
Squibb Co. v. Teva Pharms. USA, Inc., 752 F.3d 967, 977 (Fed. Cir. 2014).
The only comparison of the invention with Rychak is attorney
argument comparing examples in the Specification with an example in
Rychak. Appeal Br. 22. As the Examiner noted, this is not a proper
comparison as the binding ligands are different which would affect the
binding levels achieved. Ans. 15.
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Moreover, while Appellant argues that the results are unexpected,
Appellant offers no evidence to support that argument. Appeal Br. 24.
“Attorney’s argument in a brief cannot take the place of evidence.” In re
Pearson, 494 F.2d 1399, 1405 (CCPA 1974).
Conclusion
Based on the foregoing we conclude that a preponderance of the
evidence supports the Examiner’s conclusion that the subject matter of
claims 1−4, 6−23, 25, 28−29, 32−36, 38−50, 52, 55−56, 59−64, and 70
would have been obvious to one of ordinary skill in the art at the time the
invention was made over Rychak combined with Unger.
CONCLUSION
The Examiner’s rejection is affirmed.
More specifically, the rejection of claims 1−4, 6−23, 25, 28−29,
32−36, 38−50, 52, 55−56, 59−64, and 70 under 35 U.S.C. § 103 as
unpatentable over Rychak in view of Unger is affirmed.
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
1−4, 6−23,
25, 28−29,
32−36,
38−50, 52,
55−56,
59−64, 70
103 Rychak, Unger 1−4, 6−23,
25, 28−29,
32−36,
38−50, 52,
55−56,
59−64, 70

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TIME PERIOD FOR RESPONSE
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a). See 37 C.F.R.
§ 1.136(a)(1)(iv).
AFFIRMED