Ex Parte Hoerr et al

Patent Trial and Appeal Board

Oct 16, 2017

13492787 (P.T.A.B. Oct. 16, 2017)

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
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APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
13/492,787 06/08/2012 Ingmar Hoerr CRVC.P0040US.C1 2438
108197 7590 10/18/2017
Parker Highlander PLLC
1120 South Capital of Texas Highway
Bldg. 1, Suite 200
Austin, TX 78746
EXAMINER
DUNSTON, JENNIFER ANN
ART UNIT PAPER NUMBER
1636
NOTIFICATION DATE DELIVERY MODE
10/18/2017 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):
docket @ phiplaw .com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte INGMAR HOERR, JOCHEN PROBST, THOMAS KETTERER,
and BIRGIT SCHEEL1
Appeal 2016-000394
Application 13/492,787
Technology Center 1600
Before ERIC B. GRIMES, RICHARD J. SMITH,
and JOHN E. SCHNEIDER, Administrative Patent Judges.
SCHNEIDER, Administrative Patent Judge.
DECISION ON APPEAL
This is an appeal under 35 U.S.C. § 134(a) involving claims to
method using a nucleic acid adjuvant in a vaccine which have been rejected
for obviousness-type double patenting, as indefinite, for having an improper
Markush group, and as obvious. We have jurisdiction under 35 U.S.C.
§ 6(b).
We AFFIRM.
1 Appellants identify the Real Party in Interest as CureVac Gmbh. Appeal
Br. 3.
Appeal 2016-000394
Application 13/492,787
STATEMENT OF THE CASE
Adjuvants are often added to vaccines to increase and/or influence an
immune response. Spec. 1—2. Some adjuvants, however, can have serious
side effects. Spec. 2—\. The Specification describes the use of certain
nucleic acids as adjuvants. Spec. 5—6.
Claims 1—4, 6—9, 12—16, 18—22, 25, 30, 31, and 40-42 are on appeal.
Claim 1 is the sole independent claims and reads as follow:
1. A method of stimulating an immune response to a
disease antigen, comprising administering to a patient in need
thereof a composition comprising:
(a) the disease antigen or a disease antigen nucleic acid
encoding the disease antigen; and
(b) a pharmaceutically effective amount of an adjuvant
nucleic acid molecule comprising the sequence of formula (I):
GXmG
wherein:
G is guanosine;
X is uridine;
m is an integer and is at least 8;
provided, however, that: guanosine, uridine, adenosine,
thymidine, or cytidine positions in the adjuvant nucleic
acid molecule maybe substituted with an analogue of
these nucleotides selected from 1-methyl-adenosine, 2-
methyl-adenosine, 2-methylthio-N6-isopentenyl-
adenosine, N6-methyl-adenosine, N6-isopentenyl-
adenosine, 2-thio-cytidine, 3-methyl-cytidine, 4-acetyl-
cytidine, 2,6-diaminopurine, 1-methyl-guanosine, 2-
methyl-guanosine, 2,2-dimethyl-guanosine, 7-methyl-
guanosine, inosine, 1-methyl-inosine, dihydro-uridine, 4-
thio-uridine, 5-carboxymethylaminomethyl-2-thio-
uridine, 5-(carboxyhydroxylmethyl)-uridine, 5-fluoro-
uridine, 5-bromo-uridine, 5-carboxymethylaminomethyl-
uridine, 5-methyl-2-thio-uridine, N-uridine-5-oxyacetic
acid methyl ester, 5-methylaminomethyl-uridine, 5-
2
Appeal 2016-000394
Application 13/492,787
methoxyaminomethyl-2-thio-uridine, 5
methoxycarbonylmethyl-uridine, 5-
methoxy-uridine, uridine-5-oxyacetic acid methyl ester,
uridine-5-oxyacetic acid (v), queosine, beta-D-mannosyl-
queosine, and wybutoxosine; and phosphate moieties
may be substituted with phosphoramidates,
phosphorothioates, peptide nucleotides, or
methylphosphonates; and
wherein the immune response to the disease antigen or disease
antigen nucleic acid is greater than if the patient was provided
the disease antigen or disease antigen nucleic acid without the
adjuvant nucleic acid.
The claims stand rejected as follows:
Claims 1—4, 6—9, 12—16, 18—22, 25, and 40-42 have been rejected for
obviousness-type double patenting over claims 63—65 of Application No.
12/672,4422 in view of Diebold.3
Claims 13, 15, 20, 21, and 25 have been rejected for having an
improper Markush group.
Claims 16, 30, and 31 have been rejected under 35 U.S.C. § 112,
second paragraph, as being indefinite.
Claims 1—4, 6, 7, 18—22, 25, and 40-42 have been rejected under 35
U.S.C. § 103(a) as unpatentable over Diebold.
Claims 8, 9, and 13—16 have been rejected under 35 U.S.C. § 103(a)
as unpatentable over Diebold in view of Bayer.4
2 Claims 63—65 of Application No. 12/672,442 were cancelled by an
Amendment filed on Aug. 6, 2015, rendering this rejection moot.
3 Diebold et al., WO 2007/042554 A2, published Apr. 19, 200 (“Diebold”).
4 Bayer et al., EP 1564291 A2, published Oct. 8, 2004 (“Bayer”). Citations
are to the English translation.
3
Appeal 2016-000394
Application 13/492,787
Claims 8, 12, and 16 have been rejected under 35 U.S.C. § 103(a) as
unpatentable over Diebold in view of Jiang.5
IMPROPER MARKUSH GROUP
Issue
The issue with respect to this rejection is whether a preponderance of
evidence supports the Examiner’s conclusion that claims 13, 15, 20, 21, and
25 recited an improper Markush group.
The Examiner finds that each of claims 13, 15, 20, 21, and 25 contain
an improper Markush group in that the members of each of the groups do
not share a common structure and a common use. Final Act. 8—12.
Appellants argue that the member of each of the groups share a
common property that is mainly responsible for their function. Appeal Br.
5-6.
Appellants have the better argument. The Examiner improperly
requires that all members of the Markush groups have a common structure
and a common function. Final Act. 8. This is not the law. A Markush group
is proper if all the members share a common structure or a common
function. See In re Harms eh, 631 F2d 716, 721—22 (CCPA 1980)(Markush
group proper where all the members are dyes.) As Appellants have
demonstrated, the members of each of the Markush groups share a common
function. Appeal Br. 6. Thus, the groups are proper. For this reason we
reverse the rejection based on improper Markush groups.
5 Jiang et al., WO 03/066649 Al, published Aug. 14, 2003 (“Jiang”).
4
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Application 13/492,787
INDEFINITENES
Appellants concede that this rejection is proper. Appeal Br. 6. We
therefore affirm the rejection for indefiniteness.
OBVIOUSNESS
DIEBOLD
Issue
The issue with respect to this rejection is whether a preponderance of
the evidence supports the Examiner’s conclusion that claims 1—4, 6, 7, 18—
22, 25, and 40-42 would have been obvious to one skilled in the art over
Diebold.
The Examiner finds that Diebold teaches a method for treating or
preventing an infectious disease by administering a composition containing a
single-stranded RNA oligonucleotide having the formula Y(U)PY where Y is
independently selected from a non-uracil-containing nucleotide and p is an
integer from 4 to 12 (see FF1). Final Act. 17. The Examiner finds that
while Diebold does not teach that Y is guanosine, Diebold does teach that Y
is a non-uracil-containing residue which would include adenine, cytosine,
guanine, and thymidine. Final Act. 18. The Examiner concludes that:
One of skill in the art would have recognized that the
nucleotides adenine, cytosine and guanine are non-uracil-
containing residues. Given the finite number of possibilities for
Y, and the teaching in Diebold that Y may be any non-uracil-
containing nucleotide, it would have been obvious to one of
ordinary skill in the art select guanosine as each Y in order to
achieve the predictable result of providing an oligonucleotide
defined by the formula of Diebold et al for use in the method.
One would have a reasonable expectation of success in selecting
guanosine, because the options for the position are limited, and
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Diebold et al teach that Y can be any non-uracil-containing
nucleotide.
Final Act. 18—19.
Appellants contend that Diebold does not provide any guidance which
would lead one skilled in the art to select the claimed nucleic acids. Appeal
Br. 7—12. Appellants argue that the Examiner’s obvious to try rationale is
improper. Appeal Br. 13—15. Appellants contend that there is sufficient
evidence of unexpected results to overcome any prima facie case of
obviousness. Appeal Br. 15—17.
Findings of Fact
We adopt the Examiner’s findings as our own, including with regard
to the scope and content of, and motivation to modify or combine, the prior
art. The following findings are included for emphasis and reference
purposes.
FF1. Diebold teaches:
in another embodiment, the . . . present invention provides a
single stranded oligonucleotide consisting of between 10 and 50
nucleotides and comprising the sequence: Y(U)PY, wherein each
U is independently selected from a uracil-containing nucleotides,
each Y is independently selected from a non-uracil-containing
nucleotide; and p is an integer greater than 4. More preferred is
when p is an integer greater than 5, 6, 7, 8, 9, 10, 11 or 12. In
each of these described embodiments, it is preferred that each U
is uridine.
Diebold 5,11. 9-15.
FF2. Diebold states that:
The present invention also provides a composition comprising an
isolated single stranded oligonucleotide of between 10 and 50
nucleotides in length, and comprising a sequence selected from:
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Application 13/492,787
UUU-(X)n-UUU, UU-X-UU-X-UU, or Y(U)PY, wherein each U
is independently selected from a uracil-containing nucleotide;
each X is independently selected from any nucleotide; each Y is
independently selected from any non-uracil-containing
nucleotide; n is an integer from 1 to 4; and p is an integer greater
than 4; and a pharmaceutically acceptable carrier.
Diebold 7,11. 17-23.
FF3. Diebold goes on to teach that “in another embodiment, the
TLR8 agonist oligonucleotide further comprises a sequence selected from
UUU-(X)n-UUU, UU-X-UU-X-UU, or Y(U)PY.” Diebold 11,11. 4-5.
FF4. Diebold teaches that “[i]n another preferred embodiment, said
oligonucleotide comprises the sequence Y(U)PY, and p is an integer greater
than 9. In each of these described embodiments, it is preferred that each U is
uridine.” Diebold 22,11. 26—28. (emphasis added).
FF5. Diebold teaches that:
Preferably, a composition of this invention comprises an
effective amount of a) a single-stranded oligonucleotide
consisting of between i) 10 and 50 nucleotides and comprising
a sequence selected from: UUU-(X)n-UUU, or UU-X-UU-X-
UU, or Y(U)pY, wherein: each U is independently selected
from a uracil-containing nucleotide; each X is independently
selected from any nucleotide; n is an integer from 1 to 4; and p
is an integer greater than 4; or ii) 11 and 50 nucleotides and
comprising a sequence selected from: GGG-(X)n-GGG, GG-X-
GG-X-GG, or Z(G)pZ, wherein each G is independently
selected from a guanine-containing nucleotide; each X is
independently selected from any nucleotide; each Z is
independently selected from any non-guanine nucleotide; n is
an integer from 1 to 4; and p is an integer greater than 4; and b)
a pharmaceutically-acceptable carrier (a "pharmaceutical
composition").
Diebold 31,11. 17—27. (emphasis added).
FF6. Claim 1 of Diebold reads
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1. A single-stranded oligonucleotide consisting of
between 10 and 50 nucleotides and comprising a sequence
selected from UUUr -(X)n-UUUr, or UU-X-UU-X-UU, or
Y(U)P Y, wherein:
each U is independently selected from a uracil-containing
nucleotide;
each Y is independently selected from a non-uracil-
containing nucleotide
each X is independently selected from any nucleotide;
r is an integer from 1 to 3;
n is an integer from 1 to 4; and
p is an integer greater than 4; and
wherein said oligonucleotide comprises at least one non­
uracil-containing nucleotide or at least one non-natural linkage.
Diebold 64,11. ^14.
FF7. Claim 12 of Diebold reads “12. The oligonucleotide
according to claim 1, wherein said oligonucleotide comprises the
sequence Y (U)p Y, and p is an integer greater than 9.” Diebold 65,11.
13-14.
FF8. Diebold teaches that guanosine rich regions display
enhanced ability to agonize TLR8. Diebold 24,11. 5—6.
Principles of Law
[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).
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“The fact that some titanium compounds function more effectively,
and that the exact magnitude of the increased catalytic activity might not be
predictable, does not preclude a conclusion of obviousness. Only a
reasonable expectation of success, not absolute predictability, is necessary
for a conclusion of obviousness.” In reLongi, 759 F.2d 887, 897 (Fed. Cir.
1985).
“[T]he question is whether there is something in the prior art as a
whole to suggest the desirability, and thus the obviousness, of making the
combination, not whether there is something in the prior art as a whole to
suggest that the combination is the most desirable combination available.”
In re Fulton, 391 F.3d 1195, 1200 (Fed. Cir. 2004) (citation and quotation
marks omitted).
Picking one of a finite number of known solutions to a known
problem is obvious. KSRInt’l Co. v. Teleflex Inc., 550 U.S. 398, 421
(2007).
“The prior art’s mere disclosure of more than one alternative does not
constitute a teaching away from . . . alternatives because such disclosure
does not criticize, discredit, or otherwise discourage the solution claimed.”
In re Fulton, 391 F.3d 1195, 1201 (Fed. Cir. 2004).
“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).
[B]y definition, any superior property must be unexpected to be
considered evidence of non-obviousness. Thus, in order to
properly evaluate whether a superior property was unexpected,
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Application 13/492,787
the [fact-finder] should have considered what properties were
expected. Here, Pfizer’s evidence must fail because the record
is devoid of any evidence of what the skilled artisan would have
expected.
Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1371 (Fed. Cir. 2007) (citations
omitted).
“[I]t is well settled that unexpected results must be established by
factual evidence. ‘Mere argument or conclusory statements in the
specification does not suffice.’” In re Geisler, 116 F.3d 1465, 1470 (Fed.
Cir. 1997) (quoting In re De Blauwe, 736 F.2d 699, 705 (Fed. Cir. 1984)).
Analysis
We find the Examiner has established that the claims would have been
obvious over Diebold. Appellants have not produced evidence showing, or
persuasively argued, that the Examiner’s determinations on obviousness are
incorrect. Only those arguments made by Appellants 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)(l)(iv) (2015). We have identified claim 1
as representative; therefore, all claims fall with claim 1. We address
Appellants’ arguments below.
Appellants contend that Diebold does not provide any teaching or
suggestion to develop a nucleotide having the structure recited in the present
claims. Appeal Br. 7. Appellants argue that Diebold presents a vast array of
possibilities and does not provide a motivation to select the claimed
structure. Appeal Br. 7—8.
We have considered Appellants’ arguments and find them
unpersuasive. The Examiner bases the rejection, in part, on the teaching in
Diebold of the use of nucleotides having the structure Y(U)PY “where each
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Y is independently selected from a non-uracil-containing nucleotide; and p
is an integer greater than 4, preferably greater than 5, 6, 7, 8, 9, 10, 11 or 12,
where each U is preferably uridine.” Final Act. 17. This structure is recited
numerous times by Diebold as one of the nucleotides of the invention, FF1—
3, and is even listed as a preferred embodiment. FF4—5. Diebold
specifically claims the structure cited by the Examiner. FF6&7. We agree
with the Examiner that the teachings of Diebold would lead one skilled in
the art to use a nucleotide having the recited structure. Ans. 7.
Appellants suggest that Diebold’s teaching of polyU nucleotides
teaches away from the present invention. Appeal Br. 8—9. We are
unpersuaded. While Diebold may prefer polyU nucleotides, that alone is not
a teaching away from using other structures including those claimed by
Appellants. Appellants have not pointed to anything in Diebold which
“criticize[s], discredits], or otherwise discourage[s] the solution claimed.”
In re Fulton, 391 F.3d at 1201.
Appellants argue that the Examiner’s obvious to try analysis is
flawed. Appeal Br. 13. Appellants argue that Diebold does not present a
finite number of solutions. Appeal Br. 14. Appellants also argue that there
is no expectation of success and the art is unpredictable. Appeal Br. 15.
Appellants’ arguments are unpersuasive. As discussed above, there is
ample guidance in Diebold to lead one skilled in the art to use a nucleotide
having the general structure Y(U)PY. We agree with the Examiner that
Diebold presents a limited number of variables for the recited structure.
Ans. 9. This coupled with the teaching that selection of guanosine for Y
would enhance immune stimulation would lead one skilled in the art to the
claimed structure. Id., FF8.
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Appellants contend that they have presented evidence of unexpected
results which rebuts the Examiner’s prima facie case of obviousness.
Appeal Br. 15—17. Appellants contend that the evidence shows that long
polyU tracts (at least 8 uridines) with guanosine ends results in enhanced
immune response and that this result is unexpected. Id.
We have considered Appellants’ evidence of unexpected results and
find it unpersuasive. As the Examiner points out, the increased immune
response reported in the Declaration of Dr. Hoerr6 would be expected from
the teachings of Diebold. Ans. 14. For example Diebold teaches that
“[generally the greater the number of uracil-containing nucleotides present
within an oligonucleotide, the greater its ability to stimulate TLR7.”
Diebold 23,11. 2—3. TLR proteins “act as key signaling elements in innate
immunity.” Diebold 16,11. 5—8. Moreover Diebold specifically teaches and
claims oligonucleotides having at least 9 uracil-containing units. FF4 & 7.
With respect to the data in Vollmer,7 we agree with the Examiner that
the data does not compare the claimed subject matter with the closest prior
art. Ans. 16—17. The data is therefore insufficient to overcome the
Examiner’s conclusion of obviousness.
Conclusion of Law
We conclude that a preponderance of the evidence supports the
Examiner’s conclusion that claim 1 would have been obvious over Diebold.
6 Declaration under 37 C.F.R. § 1.132, filed Feb. 27, 2014.
7 Vollmer et al., WO 2008/139262 A2, published Nov. 20, 2008
(“Vollmer”).
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Application 13/492,787
Claims 2—4, 6, 7, 18—22, 25, and 40-42 have not been argued
separately and therefore fall with claim 1. 37 C.F.R. § 41.37(c)(l)(iv).
DIEBOLD COMINED WITH BAYER OR JIANG
Appellants’ only argument with respect to these rejections is that the
secondary references do not address the deficiencies of Diebold. Appeal Br.
17—18. As discussed above, the teachings of Diebold are not deficient. We
therefore affirm these rejections.
SUMMARY
The rejection for obviousness-type double patenting is dismissed as
moot.
The rejection for improper Markush groups is reversed.
The rejection under 35 U.S.C. § 112, first paragraph for indefmiteness
is affirmed.
The rejections under 35 U.S.C. § 103(a) are affirmed.
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).
AFFIRMED
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