Ex Parte Hoerr et al

Patent Trial and Appeal Board

Oct 16, 2017

11914945 (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
www.uspto.gov
APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO.
11/914,945 07/07/2008 Ingmar Hoerr CRVC.P0025US 2012
108197 7590 10/18/2017
Parker Highlander PLLC
1120 South Capital of Texas Highway
Bldg. 1, Suite 200
Austin, TX 78746
EXAMINER
LONG, SCOTT
ART UNIT PAPER NUMBER
1633
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 and STEVE PASCOLO1
Appeal 2016-001745
Application 11/914,945
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 for expressing RNA in an organism which have been rejected as
obvious.2 We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.
STATEMENT OF THE CASE
Molecular-medical processes, such as gene therapy and
genetic vaccination, play a major role in the therapy and
1 Appellants identify the Real Party in Interest as CureVac Gmbh. Appeal
Br. 3.
2 Oral arguments relating this appeal were heard on Oct. 10, 2017. A
transcript of the hearing will be added to the file when it becomes available.
Appeal 2016-001745
Application 11/914,945
prevention of numerous diseases. Such processes are based on
the introduction of nucleic acids into the patient's cells or tissue,
followed by processing of the information coded for by the
nucleic acids that have been introduced, that is to say
translation into the desired polypeptides or proteins. Both DNA
and RNA come into consideration as nucleic acids that can be
introduced.
Spec. 1,11. 9-14. The Specification describes a method and system for
improving the incorporation of RNA into a host organism. Spec. 3.
Claims 39^15, 48-52, 63-68, and 83-93 are on appeal. Claim 85 is
the sole independent claims and reads as follows:
85. A method of expressing an mRNA in an organism
comprising:
a) obtaining an aqueous mRNA injection solution
comprising a purified mRNA encoding a selected antigen, the
injection solution comprising a calcium salt; and
b) injecting the aqueous mRNA injection solution into an
organism, thereby expressing the mRNA.
The claims stand rejected as follows:
Claims 39^45, 48-52, 63-68, 83-88, and 90-93 have been rejected
under 35 U.S.C. § 103(a) as unpatentable over Herweijer3 in view of Hoerr.4
Claim 89 stand has been rejected under 35 U.S.C. § 103(a) as
unpatentable over Herweijer in view of Hoerr and Zrihan-Licht.5
3 Herweijer et al., US 2002/0165183 Al, published Nov. 7, 2002
(“Herweijer”).
4 Hoerr, et al., In vivo application of RNA leads to induction of specific
cytotoxic T lymphocytes and antibodies, 30 Eur. J. Immunol. 1 (2000)
(“Hoerr”).
5 Zrihan-Licht et al., Characterization and molecular cloning of a novel
MU Cl protein, devoid of tandem repeats, expressed in human breast cancer
tissue, 224 Eur. J. Biochem. 787-795 (1994). (“Zrihan-Licht”).
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Appeal 2016-001745
Application 11/914,945
DISCUSSION
HERWEIJER COMBINED WITHHOERR
Issue
The issue with respect to this rejection is whether a preponderance of
evidence supports the Examiner’s finding that claims 39^45, 48-52, 63-68,
83-88, and 90-93 would have been obvious over Herweijer combined with
Hoerr.
The Examiner finds that Herweijer teaches nucleic acid vaccination
methods where the nucleic acid includes mRNA. Final Act. 8-9. The
Examiner finds that Herweijer teaches that a preferred carrier for the nucleic
acid is Ringer’s solution which contains Calcium ions. Final Act. 9. The
Examiner finds that Herweijer suggests the inclusion of protamine as a
transfection agent. Id. With respect to Hoerr, the Examiner finds that Hoerr
teaches a composition containing mRNA complexed with protamine. Id.
The Examiner concludes that
It would have been obvious to the person of ordinary
skill in the art at the time the invention was made to produce a
pharmaceutical composition comprising protamine complexed
with a mRNA encoding a tumor antigen in a Ringer’s Solution.
The person of ordinary skill in the art would have been
motivated to make a composition comprising an protamine
complexed with mRNA encoding a tumor antigen and [3-globin
UTR because Hoerr et al provide explicit teaching and
suggestion to produce “mRNA vectors for polynucleotide
immunization ... to tumor-specific antigens” (abstract) and
further Herweijer suggest that Ringer's solution is a preferred
carrier. Therefore, a skilled artisan would envision as a useful
species of cancer vaccine a composition comprising protamine
complexed with mRNA encoding a tumor antigen in a Ringer's
solution.
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Appeal 2016-001745
Application 11/914,945
Additionally, regarding the rationale for combining prior
art elements according to known methods to yield predictable
results, all of the claimed elements were known in the prior art
and one skilled in the art could have combined the element as
claimed by known methods with no change in their respective
functions, and the combination would have yielded predictable
results to one of ordinary skill in the art at the time of the
invention. Each of the elements (vaccines comprising protamine
complexed with mRNA having UTR stabilizing sequences and
mRNA-protamine-Ringer's solution formulations) are taught by
Hoerr or Herweijer. It would be therefore predictably obvious
to use a combination of these elements in a mRNA vaccine.
Final Act. 10.
Appellants contend that there is no teaching in the references that
would lead on skilled in the art to combine mRNA with a calcium salt for
injection into an organism. Appeal Br. 5. Appellants argue that it is not
inherent that Ringer’s solution contains calcium in that Ringer’s solution is
sold both with and without calcium salts. Appeal Br. 6-9. Appellants also
argue that they have presented evidence of unexpected results which
overcomes any prima facie case of obviousness. Appeal Br. 9-11.
Appellants also contend that even if Herweijer taught the use of calcium,
Herweijer does not teach the use of calcium in conjunction with mRNA.
Reply Br. 3—4.
With respect to claims 63-68, Appellants argue that the references do
not teach or suggest the specific levels of calcium recited in the claims.
Appeal Br. 11-12.
With respect to claims 40, 49, 86, 92, and 93, Appellants argue that
they have produced evidence of unexpected results which overcomes any
prima facie case of obviousness. Appeal Br. 12-14.
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Appeal 2016-001745
Application 11/914,945
Finally with respect to claim 87, Appellants argue that the references
do not teach intradermal administration of the injection solution as required
by claim 87. Appeal Br. 14.
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).
“In order for a disclosure to be inherent, however, the missing
descriptive matter must necessarily be present in the parent application’s
specification such that one skilled in the art would recognize such a
disclosure.” Tronzo v. Biomet, Inc., 156 F.3d 1154, 1159 (Fed. Cir. 1998).
“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).
“[T]he burden of showing unexpected results rests on he who asserts
them. Thus it is not enough to show that results are obtained which differ
from those obtained in the prior art: that difference must be shown to be an
unexpected difference.” In re Klosak, 455 F.2d 1077, 1080 (CCPA 1972).
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Application 11/914,945
“It 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 De Blauwe, 736 F.2d 699, 705 (Fed.
Cir. 1984).
“[WJhere 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).
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 that
the claims would have been obvious over Herweijer combined with Hoerr.
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 85 as representative. We
address Appellants’ arguments below.
Appellants’ main argument rests on the issue of whether Ringer’s
solution, also known as Ringer’s lactate, contains calcium. Appellants
contend that while Herweijer mentions the use of Ringer’s solution,
Herweijer does not specifically mention that the solution contains calcium.
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Application 11/914,945
Appeal Br. 5. Appellants point to the AfCS Solution Protocols6 to show that
Ringer’s Solution is available with or without calcium. Appeal Br. 7, AfCS
Protocols 5. Appellants argue that the Ringer’s solution references in
Herweijer does not necessarily contain calcium. Appeal Br. 7-9.
We have considered Appellants’ arguments and find them
unpersuasive. The evidence of record supports the Examiner’s position that
one skilled in the art would understand that the Ringer’s solution referenced
in Herweijer contains calcium. Ans. 3-5. The AfCS protocols cited by
Appellants teach that when calcium is absent from Ringer’s solution, it is
listed as “Ringer’s solution (calcium free)” as opposed to Ringer’s solution.
AfCS Protocols 5. In addition, Appellants’ Specification teaches that “[a]
solution having the above-mentioned components sodium chloride (NaCl),
calcium chloride (CaCE), lactate, in particular sodium lactate, and optionally
also potassium chloride (KC1) is also known as ‘Ringer's solution’ or
‘Ringer's lactate’.” Spec. 8,11. 19-21. Finally, as the Examiner points out,
Monahan7, the parent of Herweijer, teaches that the Ringer’s solution used
contains calcium. Monahan col. 9,11. 64-67.
Appellants next argue that the evidence of record shows that the use
of calcium produces unexpected results. Appeal Br. 9-11. Appellants point
to Figure 2 of the instant Specification to show that the presence of calcium
produced more efficient expression of mRNA in vivo. Appeal Br. 11.
6 AfCS Solution Protocols, AfCS signaling gateway, www. signaling­
gateway. org/data/cgi-bin/Protocols.cgi?cat=3, last visited Nov. 11, 2014.
(“AfCS Protocols”).
7 Monahan et al., US 6,379,966 B2, issued Apr. 30, 2002. (“Monahan”).
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Application 11/914,945
Appellants’ arguments have been considered and are unpersuasive.
While we agree that the data shown in Figure 2 shows an increase in mRNA
expression, Appellants have offered no evidence, other than attorney
argument that the results would have been unexpected. Moreover,
Appellants have offered no data comparing their invention with the
composition described in Herweijer, the closest prior art.
Appellants contend that the teachings of Herweijer are limited to
DNA and are not applicable to mRNA. Reply Br. 3—4. We find this
argument unpersuasive. Herweijer specifically teaches that its teachings are
directed to both DNA and RNA, and particularly mRNA. Herweijer 141,
142, 162.
Claims 63—68
Appellants contend that claims 63-68 would not have been obvious in
that the references do not teach or suggest the specific levels of calcium
recited in the claims. We are not persuaded. As discussed above, Herweijer
teaches the use of a solution containing calcium and Monahan teaches
Ringer’s solution that contains 1.13 mM CaCh. Monahan col. 9,11. 64-67.
Determination of the workable ranges in not inventive. In re Aller, 220 F.2d
at 456.
Claims 40, 49, 86, 92, and 93
Appellants argue that there is evidence of record that the composition
recited in claims 40, 49, 86, 92, and 93 produce unexpected results. We are
unpersuaded. As with the prior evidence relating to the use of calcium-free
solutions, Appellants have offered no evidence relating to the use of calcium
and a polycationic peptide producing unexpected results. In addition,
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Appeal 2016-001745
Application 11/914,945
Appellants have offered no evidence comparing the claimed composition to
the closest prior art, namely Herweijer.
Claim 87
Appellants contend that claim 87 would not have been obvious in that
none of the references teaches intradermal injection of the claimed
composition. Appeal Br. 14. We ae not persuaded. Herweijer teaches that
“a variety of routes can be used to administer the immunogen (subcutaneous,
intramuscular, intradermal, intravenous and intraperitoneal.)” Herweijer
178. We agree with the Examiner that this would lead one skilled in the art
to use intradermal injection to administer the claimed composition. Ans.
10.
Conclusion of Law
We conclude that a preponderance of the evidence supports the
Examiner’s conclusion that claims 40, 49, 63-68, 85, 86, 87, 92, and 93
would have been obvious over Herweijer combined with Hoerr.
Claims 39, 41^45, 48, 50-52, 83, 84, 88, 90, and 91 have not been
argued separately and therefore fall with claim 85. 37 C.F.R.
§ 41.37(c)(l)(iv).
HERWEIJER COMBINED WITH HOERR AND ZRIHAN-LICHT
Appellants’ sole argument with respect to this rejection is that Zrihan-
Licht does not remedy the deficiencies of Herweijer or Hoerr. As discussed
above, Herweijer and Hoerr are not deficient. We therefore affirm this
rejection.
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Appeal 2016-001745
Application 11/914,945
SUMMARY
We affirm the rejections under 35 U.S.C. § 103(a).
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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