CureVac GmbH

Patent Trials and Appeals Board

Apr 9, 2020

14487425 - (D) (P.T.A.B. Apr. 9, 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.
14/487,425 09/16/2014 Florian VON DER MÜLBE CRVC.P0003US.D1 1723
108197 7590 04/09/2020
Parker Highlander PLLC
1120 South Capital of Texas Highway
Bldg. 1, Suite 200
Austin, TX 78746
EXAMINER
WOITACH, JOSEPH T
ART UNIT PAPER NUMBER
1631
NOTIFICATION DATE DELIVERY MODE
04/09/2020 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 FLORIAN VON DER MÜLBE, INGMAR HOERR, and
STEVE PASCOLO
Appeal 2019-004883
Application 14/487,425
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 29–33 and 35–45. We have jurisdiction
under 35 U.S.C. § 6(b).
We REVERSE.

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.
Appeal 2019-004883
Application 14/487,425
2
CLAIMED SUBJECT MATTER
The claims are directed to stabilizing mRNA for use in a
pharmaceutical composition. Spec.¶ 2. Claim 29, reproduced below, is
illustrative of the claimed subject matter:
29. A method for producing a stabilized mRNA comprising
synthesizing an mRNA molecule encoding a native polypeptide
sequence, wherein the mRNA encoding the polypeptide
comprises a nucleic acid sequence that has an increased
Guanine/Cytosine (G/C) content relative to the native nucleic
acid sequence encoding the polypeptide, said relative G/C
content being increased by at least 7 percentage points compared
to native nucleic acid sequence encoding the polypeptide, to
thereby produce a stabilized mRNA molecule, wherein said
increase in relative G/C content results in the elimination of at
least one destabilizing sequence element (DSE), wherein a
polypeptide encoded by said stabilized mRNA molecule exhibits
enhanced translational efficiency compared to a polypeptide
encoded from the native nucleic acid sequence.
REFERENCES
The prior art relied upon by the Examiner is:
Name Reference Date
Felgner, et al.
(Felgner)
US 5,580,859 Dec. 3, 1996
Neeper, et al.
(Neeper)
WO 01/14416 A2 Mar. 1, 2001
Seldon, et al.
(Seldon)
WO 02/064799 A2 Aug. 22, 2002
Fujimoto EP 0175960 A1 Apr. 2, 1986
GenBank, Accession No. AF125673, Human papillomavirus type 16,
isolate 16W12E, complete genome, found at
http://www.ncbi.nlm.nih.gov/nuccore/AF125673.1, last
accessed Oct. 6, 2015

Appeal 2019-004883
Application 14/487,425
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REJECTIONS
The Examiner has rejected the pending claims as follows:
Claims 29–33 and 35–45 have been rejected under 35 U.S.C. § 112,
second paragraph, and indefinite.
Claims 29–33 and 35–45 have been rejected under 35 U.S.C. § 112,
first paragraph for failure to comply with the written description
requirement.
Claims 29–33, 35–42, and 44–45 have been rejected udner35 U.S.C.
§ 103(a) as unpatentable over Neeper in view of Felgner, Seldon, GenBank
and Fujimoto
OPINION
Indefiniteness
The issue with respect to this rejection is whether the Examiner has
correctly determined that the rejected claims fail to particularly point out and
distinctly claims the subject matter the inventors regard as their invention.
The Examiner finds that the term “enhanced translational efficiency”
is indefinite in that the Specification teaches that stability and efficiency are
determined in a particular context and is relative to the specific conditions in
which it is assessed. Final Act. 3. The Examiner finds that the claims do not
recite how stability and efficiency are to be assessed. Id.
Appellant contends that the term “stabilized” is well known in the art.
Appeal Br. 4. Appellant contends that the term means “to maintain at a
given or unfluctuating level or quantity.” Id. Appellant contends that one
skilled in the art would apply this definition to the term and it is used in the
Specification and claims. Id. at 4–5.

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With respect to the term “enhanced,” Appellant contends that
[a] skilled artisan would immediately recognize[] that relative
to a RNA an enhanced translational efficiency would merely
mean that more protein translated or expressed from the RNA.
Appellants note that the claims provide a basis for measuring
"enhanced" expression (or ehanced [sic] translational
efficiency), namely, as compared to an unmodified mRNA
sequence. This is believed to provide an adequate reference
point so that the relative aspect of "enhanced" is clear.

Id. at 5.
Claims are in compliance with 35 U.S.C. § 112, second paragraph, if
“the claims, read in light of the specification, reasonably apprise those
skilled in the art and are as precise as the subject matter permits.”
Hybritech, Inc. v. Monoclonal Antibodies, Inc., 802 F.2d 1367, 1385 (Fed.
Cir. 1986).
“[T]he definiteness of the language employed must be analyzed—not
in a vacuum, but always in light of the teachings of the prior art and of the
particular application disclosure as it would be interpreted by one possessing
the ordinary level of skill in the pertinent art.” In re Moore, 439 F.2d 1232,
1235 (CCPA 1971).
We have considered the arguments advanced by the Examiner and
Appellant and conclude that Appellant as the better position. The present
claims, when read in light of the Specification and the state of the art, clearly
define the subject matter the inventor regards as his invention.
The Examiner contends that stability and enhancement must be
determined relative to a specific context and that neither the claims nor the
specification give any context for determining those limitations. Ans. 5.
The Examiner maintains that, absent such a context, the terms are indefinite.
Id.
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We are not persuaded. As Appellant points out, the comparison is
relative to the unmodified mRNA sequence. Reply Br. 5. This is clear from
the language of the claims themselves as well as from the Specification. See
Resp. Non-complaint Brief 2; Spec. ¶33. The other conditions are
irrelevant as long as they are the same for both sets of molecules. Reply Br.
5.
We conclude that the Examiner has not established that the pending
claims are indefinite.
Written Description
The issue with respect to this rejection is whether the Examiner has
established that the present claims fail to comply with the written description
requirement.
The Examiner finds that there is no support for the term “enhanced”
as it is used in connection with translation efficiency. Final Act. 6. The
Examiner finds that the Specification refers to codon optimization for
translation efficiency and the Examiner finds that this does not equate to
enhanced translation efficiency. Id. The Examiner concludes “[g]iven the
lack of specific guidance and lack of evidence that a change in G/C content
inherently enhances translation, the embodiment of enhanced translational
efficiency [is] found to be new matter.” Id. at 7.
Appellant contends that the Specification teaches that codon
optimization results in improved translational efficiency and that the use of
the term “enhanced” is synonymous with the term improved. Appeal Br. 6
(Citing Spec. ¶ 94).
“In order to satisfy the written description requirement, the disclosure
as originally filed does not have to provide in haec verba support for the
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Application 14/487,425
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claimed subject matter at issue.” Purdue Pharma L.P. v. Faulding, Inc., 230
F.3d 1320, 1323 (Fed. Cir. 2000).
We have considered the positions advanced by the Examiner and
Appellant and again conclude that Appellant has the better position. While
we agree with the Examiner that the term “enhanced” does not literally
appear in the Specification, the Specification does refer to improved
translational efficiency. Spec. ¶ 94. We agree with Appellant that when read
in context of the Specification, one skilled in the art would equate improved
with enhanced. Appeal Br. 6.
We conclude that the Examiner has not established that the term
“enhanced” is not supported by the Specification.
Obviousness
The issue with respect to this rejection is whether the Examiner has
demonstrated by a preponderance of the evidence that the subject matter of
the pending claims would have been obvious over Neeper combined with
Felgner, Seldon, GenBank and Fujimoto.
The Examiner finds that Neeper teaches DNA vaccines
papillomavirus genes which have been codon optimized for expression in a
human cellular environment. Final Act. 15. The Examiner finds that one
sequence encoding for a HPV exhibits a 23.6 % increase in G/C content
relative to the wild type. Id. The Examiner also finds that each sequence
reported inn Neeper has a maximum G/C content. Id. The Examiner finds
that Neeper teaches that the codon optimization results inn improved
expression yields relative to the wild-type sequence. Id. at 15–16.
The Examiner cites to Fujimoto to show the codons that encode for
the different amino acids. Id. at 16. The Examiner finds Seldon teaches
increasing yield by replacing infrequently used codons with more frequently
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used codons, which would include codons containing both G and C. Id. The
Examiner finds that Seldon teaches that “the starting point for optimization
of an mRNA may be a coding sequence with 100% common codons or a
sequence that contains a mixture of common and noncommon codons.” Id.
With respect to Felgner, the Examiner finds that Felgner teaches
pharmaceutical compositions comprising an aqueous carrier and a modified
mRNA that encodes for a polypeptide. Id. The Examiner finds that Felgner
teaches modifying the mRNA to provide a greater half-life. Id. The
Examiner finds that Felgner does not teach increasing G/C content to greater
than 7% relative to the wild-type mRNA. Id. at 17.
The Examiner finds that combining the teachings of Neeper and
Felgner would result in a modified mRNA having greater than 7% G/C
content. The Examiner concludes:
One would have been motivated to make such a
modification in order to receive the expected benefit of
providing mRNA encoding tumor antigens for a specific type of
cancer as taught by Neeper et al. Furthermore, one would have
made such a modification to provide mRNA with maximum
G/C content due to the replacement of rare codons with
common codons of highly expressed genes (codons recognized
by abundant cellular tRNA), which would allow for improved
expression of the HPV antigens and more specifically, Seldon
et al teach the preferred human codon usage, which has
maximal G/C content for use and expression in a human cell.
Id. at 18.
Appellant contends that there is no motivation to combine the
references. Appeal Br. 7. In support of this contention Appellant points to
our decision in Appeal 2016-005808 where we found a lack of motivation to
combined Felgner and Neeper. Id. at 8–11. Appellant contends that the
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same logic applied to the combination of references in the present appeal.
Id.
Appellant also contends that none of the references teach or suggest
modifying the mRNA to increase the G/C content to over 7% relative to the
wild-type. Appeal Br. 14. Appellant contends that the codon optimization
taught by Neeper does not necessarily result in a G/C content of over 7%
greater than the wild-type. Id.
A proper § 103 analysis requires “a searching comparison of the
claimed invention—including all its limitations—with the teaching of the
prior art.” In re Ochiai, 71 F.3d 1565, 1572 (Fed. Cir. 1995).
A party must, therefore, meet a high standard in order to
rely on inherency to establish the existence of a claim limitation
in the prior art in an obviousness analysis––the limitation at
issue necessarily must be present, or the natural result of the
combination of elements explicitly disclosed by the prior art.
Par Pharmaceuticals Inc., v. TWI Pharmaceuticals, Inc., 773 F3d 1186,
1195–96 (Fed. Cir. 2014).
Having considered the arguments presented by both the Examiner and
Appellant and the evidence of record, we conclude that the Examiner has
failed to establish that the subject matter of the present claims would have
been obvious. While we agree with the Examiner that the art generally
teaches codon optimization, the art does not teach or suggest increasing the
G/C content by at least 7 percentage points over the native nucleic acid
sequence.
The Examiner’s reliance on Neeper for this limitation is misplaced.
While Neeper discloses an example where the G/C level exceeded 7%, as
Appellant points out, the codon optimization method of Neeper does not
always lead to a G/C content of over 7%. Appeal Br. 13–15. Appellant has
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Application 14/487,425
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submitted evidence in the form of a declaration of Dr. Byrd2 showing that
the optimization technique of Neeper can result in a G/C content of less than
7%. Id. (Citing Byrd Decl.) The Declaration of Dr. Byrd demonstrates that
the optimization technique of Neeper does not inevitably lead to a G/C
content of over 7%.
The Examiner points to nothing in the remaining references that
remedies the deficiencies in Neeper. While Seldon teaches codon
optimization, which may include increased G/C content, we find nothing in
Seldon which teaches or suggests increasing G/C content to greater than 7%
relative to the native sequence. See Sheldon 26–27.
We conclude that the Examiner has not established by a
preponderance of the evidence that the subject matter of the present claims
would have been obvious over Neeper combined with Felgner, Seldon,
GenBank and Fujimoto.
CONCLUSION
The Examiner’s rejections are reversed.
More specifically,
The rejection under 35 U.S.C. §112, second paragraph for
indefiniteness is reversed.
The rejection under 35 U.S.C. § 112, first paragraph for failure to
comply with the written description requirement is reversed.
The rejection under 35 U.S.C. §103(a) as unpatentable over Neeper
combined with Felgner, Seldon, GenBank and Fujimoto is reversed.

2 Declaration Under 37 C.F.R. § 1.132, originally filed in Application
10/729,830 Dec. 15, 2014.
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Application 14/487,425
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DECISION SUMMARY
In summary:
Claims
Rejected
35 U.S.C.
§
Reference(s)/Basis Affirmed Reversed
29–33,
35–45
112 Indefiniteness 29–33,
35–45
29–33,
35–45
112 Written
Description
29–33,
35–45
29–33,
35–45
103(a) Neeper, Felgner,
Seldon, GenBank,
Fujimoto
29–33,
35–45
Overall
Outcome
29–33,
35–45

REVERSED