CureVac AG

Patent Trials and Appeals Board

Apr 21, 2020

15408339 - (D) (P.T.A.B. Apr. 21, 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.
15/408,339 01/17/2017 Mariola FOTIN-MLECZEK CRVC.P0077US.C1 6941
108197 7590 04/21/2020
Parker Highlander PLLC
1120 South Capital of Texas Highway
Bldg. 1, Suite 200
Austin, TX 78746
EXAMINER
WEHBE, ANNE MARIE SABRINA
ART UNIT PAPER NUMBER
1633
NOTIFICATION DATE DELIVERY MODE
04/21/2020 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):
docket@phiplaw.com
PTOL-90A (Rev. 04/07)
UNITED STATES PATENT AND TRADEMARK OFFICE
BEFORE THE PATENT TRIAL AND APPEAL BOARD
Ex parte MARIOLA FOTIN-MLECZEK and SӦHNKE VOSS
Appeal 2019-006668
Application 15/408,339
Technology Center 1600
Before DEBORAH KATZ, JOHN E. SCHNEIDER, and
MICHAEL A. VALEK, 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 4–9, 11–13, 16, 17, and 19–29, which
constitute all the claims pending in this application. Claims 1–3, 10, 14, 15,
and 18 have been cancelled. We have jurisdiction under 35 U.S.C. § 6(b).
We AFFIRM.2

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 CureVac AG.
Appeal Br. 3.
2 On oral hearing was held on April 1, 2020. A copy of the transcript (“Tr.”)
of the hearing has been entered into the record.
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CLAIMED SUBJECT MATTER
The claims are directed to method for stimulating an immune response
using a complexed mRNA and a naked mRNA. Claim 7, reproduced below,
is illustrative of the claimed subject matter:
7. A method of stimulating an immune response in a subject in
need thereof comprising administering to the subject an effective
amount of a composition comprising
(a) an adjuvant component, comprising at least one
mRNA, complexed with protamine; and
(b) at least one free mRNA, encoding at least one antigen,
wherein the molar ratio of RNA of the adjuvant component to
the at least one free mRNA of the second component b) is 1:1 to
1:4, for the prophylaxis and/or treatment of a disease.
REFERENCES
The prior art relied upon by the Examiner is:
Name Reference Date
Hoerr et al. WO 2008/014979 February 7, 2008
Jung et al. EP 1083232 A1 March 14, 2001
Scheel, et al., Therapeutic anti-tumor immunity triggered by injections of
immunostimulating single-stranded RNA, 36 Eur. J. Immunol. 2807
(2006)

REJECTION
The Examiner has rejected the pending claims as unpatentable under
35 U.S.C. § 103(a) over Hoerr in view of Schell and Jung.3

3 In the Answer, the Examiner indicated that claims 23 and 28 would be
allowed if rewritten in independent form, but did not withdraw the prior
rejection of those claims. Ans. 6. Appellant declined to make the proposed
amendment. Id.
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OPINION
Issue
The issue with respect to this rejection is whether a preponderance of
the evidence supports the Examiner’s conclusion that the subject matter of
the rejected claims would have been obvious to a person of ordinary skill in
the art at the time the invention was made over Hoerr combined with Scheel
and Jung.
The Examiner finds that Hoerr teaches the preparation of
immunostimulatory compositions comprising mRNA complexed with
protamine and naked mRNA. Ans. 3–4. The Examiner finds that Hoerr
does not teach the recited ratio of “protamine to RNA in the protamine/RNA
complex or the ratio of protamine complexed RNA to free mRNA encoding
MUC1.” Ans. 4.
The Examiner finds that Scheel teaches that both mRNA complexed
to protamine and naked mRNA can be used to generate anti-tumor responses
and teaches specific effective doses of both agents. Id. The Examiner finds
that Scheel teaches that 50µg of mRNA complexed with protamine and 50
µg of naked mRNA are effective. Id. The Examiner finds
since Scheel et al. teaches that 50 ug is an effective dosage for
either protamine complexed mRNA or free mRNA, it would
have been prima facie obvious to the skilled artisan at the time
of filing to combine 50 ug of each of protamine complexed
mRNA and free mRNA encoding MUCl in the
immunostimulatory pharmaceutical compositions taught by
Hoerr et al. with a reasonable expectation of success in producing
a composition with anti-tumor properties. Note that the
combination of 50 ug of protamine complexed mRNA and 50 ug
of free mRNA encoding MUCl results in a 1:1 ratio.
Id.
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The Examiner finds that Jung teaches a method for administering
vaccines comprising mRNA coding for an antigen. Id. at 5. The Examiner
finds that Jung teaches that the mRNA can be naked or complexed with
protamine. Id. The Examiner finds that Jung teaches that while freshly
isolated mRNA can be used to induce an immune response, free mRNA is
susceptible to mRNAse degradation. Id. The Examiner finds
Jung et al. provides motivation to include more free mRNA than
complexed RNA in a composition comprising protamine
complexed RNA and free mRNA as taught by Hoerr et al. since
Jung et al. teaches that unlike the protamine protected RNA, free
mRNA is susceptible to RNase degradation such that including
more free mRNA would ensure adequate mRNA delivery under
in vivo conditions where RNAses are present. As such, it would
have been prima facie to the skilled artisan reading Jung et al. to
practice the methods of Hoerr et al. by utilizing a complexed
RNA to free mRNA ratio where more free mRNA is present,
such as a 1:2 complexed RNA/free mRNA ratio in order to
compensate for RNAse degradation of the free mRNA in vivo
with a reasonable expectation of success.
Id.
Appellant contends that the Examiner has failed to make out a prima
facie case of obviousness as the cited references fail to teach or suggest all
of the elements of the claims. Appeal Br. 4–5. Appellant contends that the
references fail to teach or suggest the range of ratios of free to complexed
mRNA recited in the claims. Id. at 6. Appellant contend that the
Examiner’s conclusion with regard to the teachings of Jung are in error. Id.
Appellant argues that the free mRNA used in Jung did not encode for an
anti-tumor antigen making it significantly different from the mRNA of the
present invention. Id. Appellant contends that this difference in the mRNA
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of Jung would not lead one skilled in the art to the same composition as that
used in the claims. Id.
Appellant also contends that the evidence of secondary considerations
outweighs the Examiner’s prima facie case of obviousness. Id at 7.
Appellant contends “the combination of complexed and free mRNA
provides surprising and unexpected results that could not have been
predicted based on the cited art. In particular, the combination of protamine-
complexed and free mRNA in a ratio of 1:1 to 1:4 provides an immune
stimulating effect that far exceeds the effect produced by either free mRNA
or complexed mRNA alone.” Id. In support of this contention, Appellant
offers the declaration of Professor Brock.4 Id. Dr. Brock testified that, as
shown in example 6 of the present Specification, the addition of free mRNA
to mRNA complexed with protamine in ratios of from 1:1 to 1:4 (complexed
to free mRNA) showed a surprising enhanced immune response. Brock
Decl. ¶ 6. Dr. Brock also testified that the results of IL-2 induction reported
from example 10 are surprising. Id. ¶ 7.
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 subject matter of the claims would have been obvious to a person of
ordinary skill in the art at the time the invention was made over Hoerr
combined with Scheel and Jung. Appellants have not produced evidence
showing, or persuasively argued, that the Examiner’s determinations on

4 Declaration Under 37 C.F.R. § 1.132, filed December 15, 2017. (“Brock
Decl.”)
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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)(1)(iv) (2015). We have
identified claim 7 as representative; therefore, all claims fall with claim 7.
We address Appellant’s arguments below.
Appellant contends that Jung is not directed to an mRNA which
encodes for an anti-tumor antigen and thus would not lead on skilled in the
art to the claimed invention. Appeal Br. 6. We are not persuaded by this
argument. Claim 7 only requires that the free mRNA encode for an antigen.
Appeal Br. 15 (Claims App’x). The claim is not limited to an anti-tumor
antigen. As Appellant points out, the mRNA in Schell encoded for beta-
galactosidase and thus it meets the requirement of the claims. Appeal Br.
15; Scheel, 2809. The beta-galactosidase exhibited an anti-tumor effect,
which would lead one skilled in the art to combined it with the protamine
complexed mRNA, which also exhibited an anti-tumor effect. Scheel, 2809.
“It is prima facie obvious to combine two compositions each of which is
taught by the prior art to be useful for the same purpose, in order to form a
third composition which is to be used for the very same purpose. . . . [T]he
idea of combining them flows logically from their having been individually
taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850 (CCPA 1980).
We are similarly unpersauded by Appellant’s argument regarding the
ratios of complexed mRNA to free mRNA. Scheel teaches that both
complexed mRNA and free mRNA are effective at the same dosage, 50 µg.
Scheel, 2809. We agree with the Examiner that this would lead one skilled
in the art to use the complexed and free mRNA at those dosage levels, which
would be a 1:1 ratio. Ans. 4. We also agree with the Examiner that Jung’s
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teaching regarding the degradation of free mRNA versus complexed mRNA
would lead one skilled in the art to use higher amounts of mRNA leading to
ratio of free mRNA to complexed mRNA greater than 1:1. Ans. 5; Jung ¶¶
21, 28–29, 31–32, and 56.
We are also not persuaded by Appellant’s evidence of unexpected
results. As discussed below, the evidence presented is not commensurate
with the scope of the claims. “It is well established that the objective
evidence of nonobviousness must be commensurate in scope with the
claims.” In re Lindner, 457 F.2d 506, 508, 173 USPQ 356, 358 (CCPA
1972).
Claim 7 is directed to any mRNA complexed with protamine
combined with any free mRNA to produce any type of immune response.
Appeal Br. 15 (Claims App’x). Thus, at least with respect to those elements
of the claim, claim 7 is very broad. See Tr. 10–11. During oral argument,
counsel for Appellant admitted that the claims are broader than the data
relied upon as evidence of unexpected results. Id.
The data reported in Figure 2 of the present Specification compares a
mixture of complexed mRNA and free mRNA against free mRNA alone and
complexed mRNA alone. Spec. Fig. 2, 138–139. While we agree with Dr.
Brick that the mixtures show a reduction in tumor growth relative to the free
and complexed mRNA alone, Brock Decl. ¶ 6, as the Examiner points out,
the data also shows that the free mRNA and complexed mRNA showed no
significant effect on tumor growth. Ans. 13. Scheel, however, teaches a
free mRNA and a complexed mRNA mixture that exhibits a significant
effect on tumor growth. Scheel, Fig. 2. We agree with the Examiner that
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the data presented in Figure 2 of the Specification is not representative of all
mRNAs falling within the scope of the claims. Ans. 1–14.
Similarly, while both the free and complexed mRNA reported in
figure 10 showed some activity, the data only reports results for a 1 to 1
mixture of free and complexed mRNA. Spec. Fig. 10, 142.
Appellant contends that the complexed and free mRNA are exemplary
and that the data supports a finding of non-obviousness. Tr. 10–11. This
contention appears to be attorney argument and is not supported by any
evidence in the record that the mRNAs used were exemplary of the entire
class of mRNAs falling within the scope of claim 7. “Attorneys’ argument
is no substitute for evidence.” Johnston v. IVAC Corp., 885 F.2d 1574, 1581
(Fed. Cir. 1989).
We conclude that the Examiner has shown by a preponderance of the
evidence that the subject matter of claim 7 would have been obvious in view
of Hoerr combined with Schell and Jung. The remaining claims were not
argued separately and therefore fall with claim 7. 37 C.F.R. § 41.37(c)(iv).
CONCLUSION
The Examiner’s rejection is affirmed
DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
4–9, 11–13,
16, 17, 19–
29
103(a) Hoerr, Scheel,
Jung
4–9, 11–13,
16, 17, 19–
29

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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