JINA PHARMACEUTICALS, INC.

Patent Trials and Appeals Board

May 11, 2020

15204826 - (D) (P.T.A.B. May. 11, 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.
15/204,826 07/07/2016 Shoukath M. Ali JINA-13269.302 2938
72960 7590 05/11/2020
Casimir Jones, S.C.
2275 Deming Way Ste 310
Middleton, WI 53562
EXAMINER
PEEBLES, KATHERINE
ART UNIT PAPER NUMBER
1617
NOTIFICATION DATE DELIVERY MODE
05/11/2020 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):
docketing@casimirjones.com
pto.correspondence@casimirjones.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte SHOUKATH M. ALI, MOGHIS U. AHMAD, ATEEQ AHMAD,
SAIFUDDIN SHEIKH, and IMRAN AHMAD 1
Appeal 2019–006342
Application 15/204,826
Technology Center 1600
Before ERIC B. GRIMES, ULRIKE W. JENKS, and
JOHN G. NEW, Administrative Patent Judges.
GRIMES, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to a
process for preparing a lipid formulation of an active compound, which have
been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.

1 Appellant identifies the real party in interest as Jina Pharmaceuticals, Inc.
Appeal Br. 3. We use the word Appellant to refer to “applicant” as defined
in 37 C.F.R. § 1.42(a).
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STATEMENT OF THE CASE
“The present invention relates to new methods of preparing active
compounds complexed with lipids, and methods of using the complexes in
treating a subject.” Spec. ¶ 13. More specifically, the “invention relates to
the preparation of [a] suspension . . . in an aqueous system.” Spec. ¶ 73. In
embodiments, the methods of the invention can involve “dissolving active
compound . . . in water and mixing the dissolved antibiotic and the lipid(s)
together,” “mixing lipid(s) and sodium deoxycholate together in water and
then adding active compound,” or “mixing active compound . . . and one or
more lipids in any suitable sequence such that the resulting composition of
the present invention comprises active compound . . . and one or more
lipids.” Spec. ¶¶ 109, 110, 113.
Claims 39–49 are on appeal. Claim 39, reproduced below, is
illustrative:
39. A process for preparing a lipid formulation of an
active compound without use of an organic solvent, said
process comprising:
i) to a first aqueous medium consisting of water, or of
sodium chloride dissolved in water, or of a buffering agent
dissolved in water, adding at least one lipid in solid form and at
least one active compound in solid form, wherein said active
compound is a partially water soluble or water insoluble drug;
ii) treating the mixture consisting of said aqueous
medium, said lipid in solid form and said active compound in
solid form of step i) together to form a lipid-compound
suspension of defined particle size;
iii) lyophilizing the lipid-compound suspension of
defined particle size of step ii) to form lyophilized material; and
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iv) reconstituting said lyophilized material of step iii)
with a second aqueous medium to obtain a suspension of lipid
formulation of defined particle size, said defined particle size
having a mean particle size of less than 5 microns,
wherein said at least one lipid comprises at least one
phospholipid, and cholesterol or a cholesterol derivative
selected from the group consisting of cholesterol sulfate and
salts thereof, cholesterol hemisuccinate and salts thereof, and
cholesterol phosphate and salts thereof.

The claims stand rejected as follows:
Claims 39, 41–45, 47, and 49 under 35 U.S.C. § 103 as being
unpatentable over Muller2 in view of Haynes3 (Ans. 4–7);
Claim 40 under 35 U.S.C. § 103 as being unpatentable over Muller in
view of Haynes in view of Strott4 (Ans. 7–8); and
Claims 46 and 48 under 35 U.S.C. § 103 as being unpatentable over
Muller in view of Haynes further in view of Kurka5 further in view of
Kullenberg6 (Ans. 8–10).
OPINION
Obviousness based on Muller and Haynes
Claims 39, 41–45, 47, and 49 stand rejected under 35 U.S.C. § 103 as
being obvious over Muller and Haynes. Ans. 4. The Examiner finds that
“Muller teaches a method of making a drug carrier comprising subjecting at

2 US 5,858,410; issued Jan. 12, 1999.
3 US 5,091,187; issued Feb. 25, 1992
4 Charles A. Strott & Yuko Higashi, Cholesterol sulfate in human
physiology: what’s it all about?, J. Lipid Research 44:1268–1278 (2003).
5 CA 2,091,113; published Nov. 9, 1993.
6 US 5,084,269; issued Jan. 28, 1992.
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least one sparingly water soluble solid therapeutically active compound
dispersed in a solvent to high pressure homogenization to form particles
having an average particle diameter of between 40 - 100 nm.” Ans. 5. The
Examiner finds that “[t]he carrier comprises one or more dispersion-
stabilizing substances . . . which include soy lecithin and/or cholesterol.” Id.
The Examiner finds that Muller’s Example 9C “discloses a composition
made by exposing RMKP 22 (the sparingly soluble active compound), 0.6%
phospholipon (i.e. a phospholipid), and water to [homogenization] . . .
result[ing] in a composition with particle diameter of 0.286 microns.” Id.
The Examiner reasons that claim 39 “does not specify an order of
addition for the lipid and the drug, therefore lipid may be added first, drug
may be added first, or they both may be added simultaneously.” Ans. 12.
The Examiner finds that claim 39 does not “preclude a step wherein ‘a
solution of surfactant’ (i.e., the Phospholipon in Muller’s Example 9C) as
disclosed by Muller and the aqueous medium is formed prior to addition of
the drug in solid form.” Ans. 13.
The Examiner finds, “the MSDS sheet[7] indicates that Phospholipon
is a powder (i.e. in solid form . . . ).” Ans. 13. The Examiner thus finds,
“Phospholipon 90 is in solid form when added to the water. . . . There is
nothing else added and no description of method steps to form a solution.”
Ans. 14. The Examiner reasons that applying Muller’s statement that
“[a]lternatively, the drug powder can also be introduced into a surfactant
solution by stirring” to Example 9C renders obvious the step of forming a

7 Phospholipon 90 H Material Data Safety Sheet (MSDS), Phospholipid
(2007) (of record).
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mixture of water and Phospholipon 90 to which the drug powder is added
while stirring. Id.
The Examiner thus concludes that Muller makes obvious a process
meeting all of the limitations of claim 39 except the reconstitution step. The
Examiner finds that Haynes “discloses that lyophilized preparations of drug-
containing lecithin particles may be reconstituted in aqueous solution for
delivery.” Ans. 6. The Examiner concludes that it would have been obvious
“to resuspend the particles disclosed by Muller in aqueous solution because
this system would be compatible for multiple routes of drug administration
including oral and parenteral routes.” Id.
Appellant states that “Muller is not ambiguous about the steps
employed to form the nanosuspensions.” Appeal Br. 6. Specifically, Muller
“instruct[s] that the active compound is first mixed with a surfactant
solution.” Id. at 10. Appellant argues that “[n]either Muller nor the Office
provide any basis or argument that supports the Office’s contention that the
surfactant in the ‘surfactant solution’ of Muller can be ‘in solid form’ as set
forth in Appellant’s claim 39.” Id.
Appellant argues that according to Muller, “a surfactant solution must
be formed prior to the addition of the drug. Nowhere does Muller suggest
that solid Phospholipon 90 in water, in accordance with the Office’s
interpretation could be considered a ‘surfactant solution.’” Appeal Br. 11.
Appellant also argues that, while “claim 39 does not require simultaneous
addition of the lipid in solid form and the active compound in solid form, the
claim does recite that both are added [] in solid form to an aqueous
medium.” Id.
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Appellant argues that “claim 39 excludes adding the solid active
compound to a surfactant solution (however prepared), and excludes
forming a solution of the recited lipids prior to combination with the solid
active compound or, vice versa.” Id. Appellant concludes that the appealed
claims “exclude the process of Muller’s example 9C, and Muller does not
teach or suggest Appellant’s claimed method.” Appeal Br. 12.
We agree with the Examiner, however, that the claimed process would
have been obvious to a person of ordinary skill in the art based upon the
teachings of Muller and Haynes. Muller discloses a drug carrier comprising
particles of an active compound, having an average diameter of 10 nm to
1000 nm. Muller, Abstract. Muller states that “[s]uspensions were prepared
with a drug, which was ground in an air jet, in an aqueous surfactant
solution. . . . RMKP 22 was employed as the model drug.” Id. at 5:27–30.
In Example 9C of Muller, RMKP 22, Phospholipon,8 and water are
combined to prepare a nanosuspension “as described in example 1.” Muller
at 15:8–10. In Example 1, Muller explains that “[t]he powdered drug . . .
was rubbed in a grinding dish with a concentrated surfactant solution for
wetting, and the remaining aqua dest. was then added, while stirring.” Id. at
11:27–30. Muller states that, “[a]lternatively, the drug powder can also be
introduced into a surfactant solution by stirring.” Muller at 11:30–31.
The Examiner has cited the Phospholipon 90 MSDS as evidence that
Muller’s Phospholipon is a solid powder. Thus, it would have been obvious

8 Muller states that the composition included “0.6% Phospholipon 90%.”
Muller 15:8. However, “90%” appears to be a typo and “0.6% Phospholipon
90” appears to be intended. Cf. id. at 12:58 (“Phospholipon 90 0.6”).
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to form the “surfactant solution” suggested by Muller by adding solid
Phospholipon to water. Muller describes RMKP 22 as a powder (a solid).
Thus, preparing Example 9C of Muller according to the expressly suggested
alternative method of Example 1 adds solid lipid (Phospholipon) to water
(forming a solution), then adds solid active compound (RMKP 22) to the
solution to form a nanosuspension.
Claim 39 requires “adding at least one lipid in solid form and at least
one active compound in solid form” to a first aqueous medium. The claim
does not require the lipid to remain in solid form in the aqueous medium
until the solid active compound is added. Thus, claim 39 reads on a process
of adding a lipid in solid form to an aqueous medium, dissolving the lipid to
form a surfactant solution, and then adding an active compound in solid
form to that solution.
“[A] claim must be read in view of the specification of which it is a
part.” Renishaw PLC v. Marposs Societa’ per Azioni, 158 F.3d 1243, 1248
(Fed. Cir. 1998). As noted above, the instant Specification states that “[i]n
some embodiments, the method of the present invention involves mixing
lipid(s) and sodium deoxycholate[9] together in water and then adding active
compound.” Spec. ¶ 110. This embodiment describes mixing of lipid in
water prior to addition of active compound, as Muller teaches. Thus, claim
39, read in light of the instant Specification, does not preclude the formation
of a lipid solution prior to adding active compound to water. In Example 9C

9 “The commercial preparation of amphotericin B, FUNGIZONE is a
mixture of amphotericin B, a detergent deoxycholate, and a buffer.” Spec.
¶ 77. We thus understand sodium deoxycholate to be a detergent in the
embodiment discussed above.
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of Muller, both lipid and active compound are added to an aqueous medium
in solid form, meeting the limitations of claim 39.
Appellant argues that “Muller teaches that the surfactant must be in a
solution first, i.e., that the insoluble drug cannot be added directly to water.”
Appeal Br. 12.
Claim 39 does not require that drug be added directly to water alone.
As Appellant notes, while “claim 39 does not require simultaneous addition
of the lipid in solid form and the active compound in solid form, the claim
does recite that both are added to in solid form to an aqueous medium . . .”
Appeal Br. 11. As discussed above, Muller suggests forming a surfactant
solution—e.g., by adding powdered Phospholipon to water—then adding an
active compound in solid form. Additionally, the claim does not specify an
order of addition. “Unless the steps of a method actually recite an order, the
steps are not ordinarily construed to require one.” Interactive Gift Express,
Inc. v. CompuServe Inc., 231 F.3d 859, 875 (Fed. Cir. 2000). As noted
above, the instant Specification states that “[i]n some embodiments, the
present invention comprises mixing active compound . . . and one or more
lipids in any suitable sequence such that the resulting composition of the
present invention comprises active compound . . . and one or more lipids.”
Spec. ¶ 113, emphasis added. Thus, the instant Specification indicates that
the order of addition is not critical to the claimed method.
Appellant argues that “the process of Muller exemplified by Example
9C is labor-intensive” while “Appellant has surprisingly shown that [] a
much simpler process can be used to produce a stable nanosuspension
having particles of defined size.” Appeal Br. 12.
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This argument is unpersuasive. The preamble of claim 39 recites the
transition term “comprising.” “The transition ‘comprising’ in a method
claim indicates that the claim is open-ended and allows for additional steps.”
Invitrogen Corp. v. Biocrest Mfg., L.P., 327 F.3d 1364, 1368 (Fed. Cir.
2003). Thus, claim 39 allows for the additional steps cited by Appellant
(Appeal Br. 12), such as air-jet grinding of the drug to form a powder.
We conclude that the rejection of claims 39, 41–45, 47, and 49 under
35 U.S.C. § 103 based on Muller in view of Haynes is supported by a
preponderance of the evidence, and we therefore affirm it.

Obviousness based on Muller, Haynes, and Strott
Claim 40 stands rejected under 35 U.S.C. § 103 as being obvious over
Muller, Haynes, and Strott. Ans. 7. The Examiner finds that Muller and
Haynes are silent with respect to cholesterol sulfate, but finds that “Strott
discloses . . . that cholesterol sulfate interacts with phospholipids in a
manner similar to that observed for cholesterol and has the ability to induce
hydrocarbon ordering in lipid bilayers and to stabilize model membranes.”
Ans. 8. The Examiner concludes that it would have been obvious to use
cholesterol sulfate in Muller’s method because cholesterol sulfate is
structurally similar to the cholesterol suggested by Muller, and cholesterol
sulfate “was known to increase the stability of phospholipid structures.” Id.
We agree with the Examiner’s fact-finding and conclusion.
Appellant argues that “Strott fails to cure the deficiencies of Muller
and Haynes with respect to the process recited in Appellant’s claim 39.”
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Appeal Br. 14. We find this argument unpersuasive for the reasons
discussed above.
Appellant additionally argues that Strott “is limited in its discussion of
this compound with respect to membranes to the function of cholesterol
sulfate in cell membranes” and “[n]othing in Strott teaches or suggests what
effect cholesterol sulfate might have on solid/microcrystalline lipid
nanoparticles disclosed by Muller and Haynes.” Id.
We agree with Examiner, however, that the teachings of Strott are
properly combined with those of Muller. As the Examiner found, “Muller
discloses that combinations of cholesterol and phospholipid can be used in
the method of making the drug carrier.” Ans. 8. Specifically, Muller
suggests including “mixtures of . . . lecithins with one or more phospholipid
components, cholesterol, cholesterol palmitate, or stigmasterol.” Muller
19:8–10. As the Examiner has pointed out “cholesterol and cholesterol
sulfate were known to be structurally similar,” Ans. 8; thus, it would have
been obvious to substitute cholesterol sulfate for Muller’s cholesterol.

Obviousness based on Muller, Haynes, Kurka, and Kullenberg
Claims 46 and 48 stand rejected under 35 U.S.C. § 103 as being
obvious over Muller, Haynes, Kurka, and Kullenberg. Ans. 8.
Appellant argues that Kurka and Kullenberg “do[] not cure the
deficiencies of Muller and Haynes with respect to adding drug and lipid to a
specific selection of aqueous media.” Appeal Br. 15.
Because we do not find any deficiency in the combination of Muller
and Haynes, and Appellant has waived arguments directed to Kurka or
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Kullenberg, we affirm the rejection of claims 46 and 48 for the reasons
given by the Examiner and as discussed above.
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C. § Reference(s)/Basis Affirmed Reversed
39, 41–45,
47, 49
103 Muller, Haynes 39, 41–45,
47, 49

40 103 Muller, Haynes, Strott 40
46, 48 103 Muller, Haynes, Kurka,
Kullenberg
46, 48
Overall
Outcome
39–49
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