Ex Parte Rios

Board of Patent Appeals and Interferences

Mar 31, 2009

10667534 (B.P.A.I. Mar. 31, 2009)

UNITED STATES PATENT AND TRADEMARK OFFICE
__________

BEFORE THE BOARD OF PATENT APPEALS
AND INTERFERENCES
__________

Ex parte ADAN RIOS
__________

Appeal 2009-1967
Application 10/667,534
Technology Center 1600
__________

Decided:1 March 31, 2009
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Before DEMETRA J. MILLS, ERIC GRIMES, and JEFFREY N.
FREDMAN, Administrative Patent Judges.

MILLS, Administrative Patent Judge.

DECISION ON APPEAL

1 The two-month time period for filing an appeal or commencing a civil
action, as recited in 37 C.F.R. § 1.304, begins to run from the decided date
shown on this page of the decision. The time period does not run from the
Mail Date (paper delivery) or Notification Date (electronic delivery).

Appeal 2009-1967
Application 10/667,534

STATEMENT OF CASE
This is an appeal under 35 U.S.C. § 134. The Examiner has rejected
the claims for lack of written description. We have jurisdiction under 35
U.S.C. § 6(b). The following claim is representative.

48. A method of eliciting an immune response comprising:
obtaining a viral particle comprising a reverse transcriptase that has
been inactivated by binding said reverse transcriptase with one or
more azido-lableled compounds and then irradiating said reverse
transcriptase; and
administering the viral particle to a subject, wherein an immune
response is elicited in the subject.

Ground of Rejection
Claims 40-50 are rejected under 35 U.S.C. §112, first paragraph for
lack of written description.

References Relied on by Appellant
Flavell, “Retroelements, reverse transcriptase and evolution,” Comp.
Biochem. Physiol., Vol. 110B, No. l, pp. 3-15 (1995).

Boeke, “The unusual phylogenetic distribution of retrotransposons: A
hypothesis,” Genome Res., Vol. 13, pp. 1975-1983 (2003).

Nakamura et al., “Telomerase catalytic subunit homologs from fission
yeast and human,” Science, Vol. 277 (August 15, 1997).

Springer et al., “Phylogenetic relationships of reverse transcriptase and
Rnase H sequences and aspects of genome structure in the gypsy group of
retrotransposons,” Mol. Biol. Evol., 10 (6), pp. 1370-1379 (1993).

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Application 10/667,534
Lingner et al., “Reverse transcriptase motifs in the catalytic subunit of
telomerase,” Science, Vol. 276, p. 561 (1997).

Valverde-Garduno et al., “Functional analysis of HIV-1 reverse
transcriptase motif C: site-directed mutagenesis and metal cation
interaction,” J. Mol. Evol., 47(1), pp. 73-80 (1988).

Seifarth et al., “Rapid identification of all known retroviral reverse
transcriptase sequences with a novel versatile detection assay, AIDS
Research and Human Retroviruses,” Aids Research and Human
Retroviruses, Vol. 16, No. 8, pp. 721-729 (2000).

ISSUE
The Examiner argues that the claims are broad and the disclosure fails
to teach the inactivation of any other retroviral or retrotransposon reverse
transcriptases (RTs) other than HIV-1.
The Applicant argues that
HIV is a retrovirus and a unique aspect of retrovirus replication is the
conversion of a single-stranded RNA from the virus genome into a
doublestranded DNA molecule that must integrate into the genome of
the host cell prior to the synthesis of viral proteins and nucleic acids
(Specification, p. 3, ln. 4-12). Accordingly, all retroviruses
possess a reverse transcriptase enzyme, which converts the RNA of
their genetic material into DNA (Specification, p. 3, ln. 14-16).
Furthermore, since all reverse transcriptases prime the synthesis of
new DNA from tRNA, which is a molecule with abundant secondary
structure strongly associated with the enzyme, it is generally accepted
that the catalytic unit among reverse transcriptases is phylogenetically
conserved.

(App. Br. 3.)

The issue is: Has the Examiner shown that the disclosure does not
convey with reasonable clarity to those skilled in the art, that the inventor
was in possession of the invention, and is there written descriptive support in
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Application 10/667,534
the Specification for inactivation of reverse transcriptases generally and for
the method of illiciting an immune response, as claimed?

FINDINGS OF FACT
The Examiner finds that:
1. “The claims of the instant application are directed toward a method of
eliciting an immune response by obtaining a viral particle comprising a
reverse transcriptase (RT) that has been inactivated with one or more azido-
labeled compounds followed by irradiation.” (Ans. 6.)
2. “The broadest claims are not directed toward any particular source of the
RT enzyme. Perusal of the disclosure demonstrates that applicants were
clearly focused on HIV-1, in particular for the development of an efficacious
vaccine.” (Ans. 6.)
3. In summarizing his invention (Spec. p. 2, lines 11-19) [A]pplicants stated
the following:
The present invention relates generally to the fields of virology,
immunology, disease treatment, and prevention. More particularly, it
concerns HIV particles with inactivated reverse transcriptase, methods
of inactivation, and the use of such particles to prepare components of
HIV and to elicit effective immunological responses to HIV. These
immune responses are useful in producing diagnostic reagents, assays,
and kits for the diagnosis of HIV and related retroviral disease,
providing protection from an HIV challenge, and assisting an HIV-
infected individual in controlling the replication of the virus. Methods
of inactivation are useful for preventing disease through decreasing
the risk of infection associated with exposure to HIV infected tissues
and materials. [p. 2, 1. 11-19]

(Ans. 6-7.)

4. “The [S]pecification in describing the related art discusses only HIV.”
(Ans. 7.)
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Application 10/667,534
7. No other retroviruses are described to any extent in the Specification.
5Ans. 7.)
6. “The [S]pecification discusses HIV biology and the worldwide
geographic distribution of the virus (pp. 16-18). All of the examples
provided in the [S]pecification involve HIV-1 RT (e.g., see Example 1:
photoinactivation of HIV-1 RT [p. 30-31; Example 2: inactivation of HIV
particles and infected cells [p. 31]).” (Ans. 7-8.)
7. There is no mention of any other retroviral or retrotransposon RTs in the
Specification. (Ans. 8.)
8. The Retroviridae encompass several genera including the avian-
leukosis-sarcoma viruses (e.g., Rous sarcoma virus (RSV), avian
myeloblastosis virus (AMV), avian erythroblastosis virus (AEV),
avian myelocytomatosis virus (MC)), mammalian C-type retroviruses
(e.g., Moloney murine leukemia virus (Mo-MLV), Harvey murine
sarcoma virus (Ha-MSV), Abelson murine leukemia virus (A-MuLV)
, feline leukemia virus (FeLV), reticuloendotheliosis virus (REV),
spleen necrosis virus (SNV)), B-type viruses (e. g., Mouse mammary
tumor virus (MMTV) ) , D-type viruses (e. g., Mason-Pfizer monkey
virus (MPMV) , “SAIDS” viruses), HTLV-BLV viruses (e. g., Human
T-cell leukemia virus (HTLV-I and -II ), Bovine leukemia virus
(BLV)), lentiviruses (e.g., human immunodeficiency virus (HIV-1 and
-2 simian immunodeficiency virus (SIV), feline immunodeficiency
virus (FIV), bovine immunodeficiency virus (BIV), Visna/maedi
virus, caprine arthritis-encephalitis virus (CAEV), equine infectious
anemia virus (EIAV)), and spumaviruses (e. g., simian foamy virus
(SFV), human foamy virus (HFV), human spumaretrovirus (HSRV)).
The [S]pecification fails to discuss any other virus other than HIV.
Once again, there is no indication that [A]pplicants contemplated
inactivating RT from any of the aforementioned viruses except HIV-1.

(Ans. 8.)

9. “The disclosure fails to teach the inactivation of any other retroviral or
retrotransposon RTs other than HIV-1.” (Ans. 8.)
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Application 10/667,534
10. The Examiner concludes that “the skilled artisan would conclude that
applicants were not in possession of the full genus claimed.” (Ans. 8.)
11. According to the Specification, page 13, the immune response may be a
humoral response, a cellular response or both a humoral and cellular
response. “The cellular response may be a CD8+ T cell response, a CD4+
T cell, or both a CD8+ T cell and a CD4+ cell response,” however,
throughout the [S]pecification, the disclosure particularly is directed to a
protective immune response to HIV. (Spec. 13.)
12. The Specification, page 16, ll. 20-25 provides that, it is “of importance
to note that the methodology of the present invention is applicable to any
retrovirus which may be associated with any animal or human disease
as a method for development of effective immunogens and preventive
vaccines.”
13. “In one embodiment the RT is inactivated by one or more compounds
that binds the RT and then irradiating bound RT with UV light. . . . . In one
embodiment of the compound that binds to RT is an azido labeled
compound.” (Spec. 12: 8-18.)
14. Lingner, Figs. 2 and 3 evidence that reverse transcriptase domains are
shared by multiple reverse transcriptases, with several highly conserved
regions. (Lingner, 562.)

PRINCIPLES OF LAW
“[The written description] inquiry is a factual one and must be
assessed on a case-by-case basis.” Purdue Pharma L.P. v. Faulding, Inc.,
230 F.3d 1320, 1323 (Fed. Cir. 2000). The Specification need not describe
the invention in the same terms used in the claims, but the disclosure must
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Application 10/667,534
convey with reasonable clarity to those skilled in the art that the inventor
was in possession of the invention. See id.
The degree of specificity required to adequately describe an invention
“varies with the nature and scope of the invention at issue, and with the
scientific and technologic knowledge already in existence.” Capon v.
Eshhar, 418 F.3d 1349, 1357 (Fed. Cir. 2005). See also id. at 1359
(“[W]hat is needed to support generic claims to biological subject matter
depends on a variety of factors, such as the existing knowledge in the
particular field, the extent and content of the prior art, the maturity of the
science or technology, the predictability of the aspect at issue, and other
considerations appropriate to the subject matter.”) See, e.g., In re Wallach,
378 F.3d 1330, 1333-34 (Fed. Cir. 2004) (an amino acid sequence supports
“the entire genus of DNA sequences” that can encode the amino acid
sequence because “the state of the art has developed” such that it is a routine
matter to convert one to the other); Univ. of Rochester v. G.D. Searle & Co.,
358 F. 3d 916, 925 Cir. 2004). (considering whether the patent disclosed the
compounds necessary to practice the claimed method, given the state of
technology); Singh v. Brake, 317 F.3d 1334, 1343 (Fed. Cir. 2002)
(affirming adequacy of disclosure by distinguishing precedent in which the
selection of a particular species within the claimed genus had involved
“highly unpredictable results”). Furthermore, an actual reduction to practice
is not required for written description. See Univ. of Rochester v. G.D. Searle
& Co., 358 F. 3d at 926. This written description requirement applies not
only to compositions of matter, but to methods as well. University of
Rochester v. G.D. Searle & Co., 358 F.3d at 926.

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Application 10/667,534
Claim Interpretation and Claim Scope
Claim 48 is directed to a method of eliciting an immune response
comprising: obtaining a viral particle comprising a reverse transcriptase that
has been inactivated by binding said reverse transcriptase with one or more
azido-labeled compounds and then irradiating said reverse transcriptase; and
administering the viral particle to a subject, wherein an immune response is
elicited in the subject.
Any immune response is encompassed by the claimed method, which
is not limited to protective immune responses. (FF 13.) The claims
encompass the use of any viral particle including a reverse transcriptase that
has been inactivated by binding the reverse transcriptase with one or more
azido-labeled compounds and then irradiated.

ANALYSIS
The Appellant argues that:
HIV is a retrovirus and a unique aspect of retrovirus replication is the
conversion of a single-stranded RNA from the virus genome into a
doublestranded DNA molecule that must integrate into the genome of
the host cell prior to the synthesis of viral proteins and nucleic acids
(Specification, p. 3, ln. 4-12). Accordingly, all retroviruses
possess a reverse transcriptase enzyme, which converts the RNA of
their genetic material into DNA (Specification, p. 3, ln. 14-16).
Furthermore, since all reverse transcriptases prime the synthesis of
new DNA from tRNA, which is a molecule with abundant secondary
structure strongly associated with the enzyme, it is generally accepted
that the catalytic unit among reverse transcriptases is phylogenetically
conserved.

(App. Br. 3.)

We conclude that the Examiner has not provided sufficient evidence
to show that, in view of the Specification, the skilled artisan would not have
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Application 10/667,534
been placed in possession of the method of the claims. In particular, the
skilled artisan would have been in possession of the general technique
disclosed in the Specification of inactivating HIV reverse transcriptase as
applicable to reverse transcriptases generally (see FF 11), which share
similar conserved structure and catalytic units. Therefore that the Examiner
has not shown that the Specification fails to adequately describe the
invention of the claims on appeal.
“The 'written description' requirement serves a teaching function, . . .
in which the public is given 'meaningful disclosure in exchange for being
excluded from practicing the invention for a limited period of time.'“
University of Rochester v. G.D. Searle & Co., Inc. , 358 F.3d 916, 922 (Fed.
Cir. 2004) (citation omitted). Another “purpose of the 'written description'
requirement is . . . [to] convey with reasonable clarity to those skilled in the
art that, as of the filing date [ ], [the applicant] was in possession of the
invention.” Vas-Cath Inc. v. Mahurkar , 935 F.2d 1555, 1563-64 (Fed. Cir.
1991). See also Enzo Biochem Inc. v. Gen-Probe Inc., 296 F.3d 1316, 1329
(Fed. Cir. 2002). The requirement is satisfied when the Specification “set[s]
forth enough detail to allow a person of ordinary skill in the art to
understand what is claimed and to recognize that the inventor invented what
is claimed.” University of Rochester, 358 F.3d at 928. It is the Examiner's
“initial burden [to] present[ ] evidence or reasons why persons skilled in the
art would not recognize in the disclosure a description of the invention
defined by the claims” (In re Wertheim, 541 F.2d 257, 263 (CCPA 1976)).
“[A]pplicants have some flexibility in the 'mode selected for compliance'
with the written description requirement” (University of Rochester, 358 F.3d
at 928); it is well settled that actual reduction to practice is not necessary to
satisfy the requirement (id., at 926).
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Application 10/667,534
Appellant argues that:
Since retroviruses cannot integrate into the genetic machinery
of the host cell without reverse transcription, the inhibition of
reverse transcriptase has as a universal consequence on the
inability of any retrovirus to integrate within the genetic
machinery of a suitable host cell. Thus, regardless of the type of
retrovirus, the inactivation of reverse transcriptase as described
in the present specification would be understood by a person of
ordinary skill in the art to be applicable to any retrovirus. The
importance of RT to retroviruses in general, is further
evidenced by the number of known anti-retroviral compounds
that interfere with RT activity (e.g., AZT [azidothymidine],
nevirapine, pyridinones, carboxanilides) (Specification, p. 3, ln.
23 to p. 4, ln. 8).

As described in the present specification, a reverse transcriptase
may be inactivated by binding the reverse transcriptase with
one or more azido-labeled compounds and then irradiating it
(see e.g., p. 12, ln. 8-9). Numerous compounds that bind to
reverse transcriptases were known in the art (see e.g.,
Specification, p. 3, ln. 23, to p. 4, ln. 11).

(App. Br. 4.)

The Examiner finds that “the various exhibits relied upon [by
Appellants]… fail to support applicants' arguments,” and that nothing in the
Specification leads the skilled artisan to a particular retrovirus. (Ans. 9.)
We find that Appellant has the better argument.
In our view, the Examiner’s own rejection evidences that the skilled
artisan would have been in possession of knowledge that the scope of
Retroviridae encompasses a number of different genera (see Ans. 8).
Further, the skilled artisan would have known that all of these well known
retrovirus species require active reverse transcriptase activity. The
Examiner's statement that “there is no indication that applicants
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Application 10/667,534
contemplated inactivating RT from any of the aforementioned viruses except
HIV-1” is not correct. Appellants’s Specification specifically states that “the
methodology of the present invention is applicable to any retrovirus which
may be associated with any animal or human disease as a method for
development of effective immunogens and preventive vaccines” (Spec. 16,
ll. 20-25; FF 12). This quotation from the Specification cannot be read as
anything other than a direct teaching to apply the claimed inactivation
method to known retrovriuses that are assocaited with human or animal
disease. At the very least, this teaching places the skilled artisan in
possession of the claimed method with known pathogenic or zoonotic
retroviruses.
The Examiner has not provided adequate evidence that the skilled
artisan would not have been in possession of known retroviruses. The
Examiner has also not adequately addressed Appellant’s argument that one
of ordinary skill in the art would have understood from the conserved
regions and similarity of function of reverse transcriptases generally, that
they could be predictably inactivated using azido-labeled compounds and
irradiation and used in the claimed method.
The evidence of record supports the Specification’s description of the
disclosed method as applicable to retroviruses generally, rather than
applicable only to HIV. In other words, the Examiner has not provided
evidence that one of ordinary skill in the art would not have understood that
azido compounds bind to reverse transcriptases generally, and that one of
ordinary skill in the art would not have expected that irradiated azido-labeled
compounds inactivate reverse transcriptases generally.
In view of the above, we find that the Examiner has not shown that
the disclosure does not convey with reasonable clarity to those skilled in the
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Application 10/667,534
art, that the inventor was in possession of the invention. The written
description rejection is reversed.
No time period for taking any subsequent action in connection with
this appeal may be extended under 37 C.F.R. § 1.136(a).

REVERSED

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FULBRIGHT & JAWORSKI L.L.P.
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