DEPARTMENT OF COMMERCE

                          Patent and Trademark Office

                        [Docket No. 970129014-8206-02]

                                 RIN 0651-XX09

                   Guidelines for the Examination of Claims
                 Directed to Species of Chemical Compositions
                    Based Upon a Single Prior Art Reference

AGENCY: Patent and Trademark Office, Commerce.

ACTION: Notice.

SUMMARY: The Patent and Trademark Office (PTO) is publishing the final
version of guidelines to be used by Office personnel in reviewing a
certain type of patent application for compliance with 35 U.S.C.    103.
The guidelines are to be used when examining claims directed to a
species or subgenus of chemical compositions when: (1) the claims have
been rejected based upon a single prior art reference, and (2) the
single prior art reference discloses a genus embracing the claimed
species or subgenus but does not expressly describe the particular
claimed species or subgenus. Because these guidelines govern internal
practices, they are exempt from notice and comment rulemaking under 5
U.S.C.    553(b)(A).

DATES: The guidelines are effective September 3, 1998.

FOR FURTHER INFORMATION CONTACT: Linda Moncys Isacson, Office of the
Solicitor, P.O. Box 15667, Arlington, Virginia 22215 or Linda S.
Therkorn, Box Comments, Assistant Commissioner for Patents, Washington,
D.C. 20231, or by facsimile transmission to (703) 305-9373 or by
electronic mail over the Internet to baird-comments@uspto.gov.

SUPPLEMENTAL INFORMATION:

Discussion of Public Comments:

Comments were received by the PTO from two different individuals and one
organization in response to the Request for Comments on the Interim
Guidelines for the Examination of Claims Directed to Species of Chemical
Compositions Based Upon a Single Prior Art Reference published February
11, 1997 (62 FR 6217). All comments have been carefully considered.

   The following comments have been substantively adopted to effect changes
in the guidelines:

   (1) A suggestion to annotate the flowchart with references to
corresponding sections of text in the guidelines was adopted.

   (2) One comment suggested that the guidelines inappropriately focussed
solely on the number of possible members of a prior art genus to
determine whether the prior art genus anticipated a claimed species or
subgenus. Attention was drawn to the discussion of In re Petering, 301
F.2d 676, 133 USPQ 275 (CCPA 1962) in the text at section II.A.4.a and
note 22, which seemed to suggest that size of the genus alone was
sufficient to support a finding of anticipation. These portions of the
guidelines have been modified to indicate that size of the genus is only
one factor to be considered in determining anticipation.

   (3) One comment suggested that the guidelines be supplemented to direct
Office personnel to consider the sufficiency of the preparative methods
disclosed in the cited reference. Failure of a prior art reference to
disclose or render obvious a method for making any composition of matter
may preclude a conclusion that the composition would have been obvious
if the disclosure is not enabling. However, once a prima facie case of
obviousness is made out by the PTO, the initial burden of going forward
with evidence to show that no process was known in the art for preparing
the compound is on the applicant. Accordingly, the guidelines have been
changed at section II.B to include consideration of sufficiency of
disclosure of preparative methods as rebuttal evidence to overcome a
prima facie case of obviousness.

   (4) One comment suggested that the language in section II.A.2 of the
guidelines and in corresponding portions of the flowchart instructing
Office personnel to make explicit findings on the similarities and
differences between "the closest prior art reference" and the claimed
species or subgenus be changed to direct findings to be made between the
"closest disclosed species or subgenus" and the claimed species or
subgenus for accuracy and clarity. This change has been made in the text.

   (5) One comment suggested that section II.A.4.d be clarified to indicate
that the utility disclosed in a reference need not be the same as the
stated utility of the claimed compound. Language has been added to
indicate that any useful property may be the basis of a finding of
motivation.

   (6) One comment suggested that language in section II.B. stating that
evidence of an unexpected property may not be sufficient to overcome a
prima facie case of obviousness, regardless of the scope of the showing,
is not accurate in view of the law. Language has been added to the
associated footnote to clarify that a showing of an unexpected property
is sufficient in most circumstances.

   The following comments have been considered but have not been adopted
for the reasons discussed below:

   (1) One comment suggested that more emphasis be placed on additional
references which may teach away from the claimed compound(s) due to a
disclosure of related compounds having or expected to have disadvantages
not possessed by the claimed compound(s). This comment was not adopted
because it focuses on "additional references," whereas the scope of
these guidelines is directed to situations involving rejections over a
single reference. The guidelines already clearly instruct Office
personnel that they must consider any additional references or evidence
of teaching away that are present.

   (2) One comment suggested that the guidelines were too limited in scope
because they focused on rejections based on a single reference as
opposed to rejections based on more than one reference. The scope of
these guidelines is intended to address a specific issue, i.e., the
situation where only one reference disclosing a genus but not the
claimed species is found. Although the principles discussed in these
guidelines are generally applicable to all rejections under 35 U.S.C.
103, the explicit scope of these guidelines will not be changed.

   (3) One comment suggested that section II.A.4.f of the guidelines
inappropriately instructs Office personnel to focus only on evidence
supporting a rejection rather than making a complete analysis. Section
II.A.4.f of the guidelines additionally instructs Office personnel to
consider the totality of the evidence in each case. Furthermore, Office
personnel are instructed in section II.B to consider whether rebuttal
evidence overcomes a prima facie case of obviousness and in section III
to reconsider all evidence in reaching a conclusion. Thus, the
guidelines presently clearly require all evidence to be considered, not
only evidence supporting a rejection.

   (4) One comment suggested that the last sentence of section II.A.4.c
assumes that a generic teaching in a reference, by itself, is never
enough to make out a prima facie case of obviousness. The referenced
language does not suggest this, but rather it merely states the general
proposition that in most cases, additional teachings of structural
similarity to the disclosed species or subgenus are necessary.
Accordingly, no change has been made.

   (5) One comment suggested that the guidelines address the significance
of the type of reference involved, i.e. whether there is a difference
between a journal publication, a U.S. Patent, a foreign patent, etc.
This suggestion has not been adopted, because for substantive analysis
under 35 U. S.C.    103, each reference should be considered for all of
its teachings, regardless of its form.

   (6) One comment suggested that the guidelines address the significance
of the presence or absence of any activity testing of disclosed species
in the reference. The guidelines already instruct Office personnel to
consider any teachings of similar properties or uses, predictability of
the technology, and any other teachings present in the reference that
would support selection of the claimed compound. Consideration of any
disclosed testing data is subsumed in these considerations.

I. Guidelines for the Examination of Claims Directed to
   Species of Chemical Compositions Based Upon a Single
   Prior Art Reference

   These "Genus-Species Guidelines" are to assist Office personnel in the
examination of applications which contain claims to species or a
subgenus of chemical compositions for compliance with 35 U.S.C.    103
based upon a single prior art reference which discloses a genus
encompassing the claimed species or subgenus but does not expressly
disclose the particular claimed species or subgenus. Office personnel
should attempt to find additional prior art to show that the differences
between the prior art primary reference and the claimed invention as a
whole would have been obvious. Where such additional prior art is not
found, Office personnel should follow these guidelines to determine
whether a single reference 35 U.S.C.    103 rejection would be
appropriate. The guidelines are based on the Office's current
understanding of the law and are believed to be fully consistent with
binding precedent of the Supreme Court, the Federal Circuit, and the
Federal Circuit's predecessor courts.

   The analysis of the guidelines begins at the point during examination
after a single prior art reference is found disclosing a genus
encompassing the claimed species or subgenus. Before reaching this
point, Office personnel should follow appropriate antecedent examination
procedures. Accordingly, Office personnel should first analyze the
claims as a whole in light of and consistent with the written
description, considering all claim limitations.1 Next, Office personnel
should conduct a thorough search of the prior art and identify all
relevant references.2 If the most relevant prior art consists of a
single prior art reference disclosing a genus encompassing the claimed
species or subgenus, Office personnel should follow the guidelines set
forth herein.

   These guidelines do not constitute substantive rulemaking and hence do
not have the force and effect of law. Rather, they are to assist Office
personnel in analyzing claimed subject matter for compliance with
substantive law. Thus, rejections must be based upon the substantive
law, and it is these rejections which are appealable, not any failure by
Office personnel to follow these guidelines.

   Office personnel are to rely on these guidelines in the event of any
inconsistent treatment of issues between these guidelines and any
earlier provided guidance from the Office.

II. Determine Whether the Claimed Species or Subgenus
    Would Have Been Obvious to One of Ordinary Skill
    in the Pertinent Art at the Time the Invention Was Made

   The patentability of a claim to a specific compound or subgenus
embraced by a prior art genus should be analyzed no differently than any
other claim for purposes of 35 U.S.C.    103.3 A determination of
patentability under 35 U.S.C.    103 should be made upon the facts of
the particular case in view of the totality of the circumstances.4 Use
of per se rules by Office personnel is improper for determining whether
claimed subject matter would have been obvious under 35 U.S.C.    103.5
The fact that a claimed species or subgenus is encompassed by a prior
art genus is not sufficient by itself to establish a prima facie case of
obviousness.6

A proper obviousness analysis involves a three step process. First,
Office personnel should establish a prima facie case of unpatentability
considering the factors set out by the Supreme Court in Graham v. John
Deere.7 If a prima facie case is established, the burden shifts to
applicant to come forward with rebuttal evidence or argument to overcome
the prima facie case.8 Finally, Office personnel should evaluate the
totality of the facts and all of the evidence to determine whether they
still support a conclusion that the claimed invention would have been
obvious to one of ordinary skill in the art at the time the invention
was made.9

   A. Establishing a Prima Facie Case of Obviousness

   To establish a prima facie case of obviousness in a genus-species
chemical composition situation, as in any other 35 U.S.C.    103 case,
it is essential that Office personnel find some motivation or suggestion
to make the claimed invention in light of the prior art teachings.10 In
order to find such motivation or suggestion there should be a reasonable
likelihood that the claimed invention would have the properties
disclosed by the prior art teachings.11 These disclosed findings should
be made with a complete understanding of the first three "Graham
factors."12 Thus, Office personnel should (1) determine the "scope and
content of the prior art"; (2) ascertain the "differences between the
prior art and the claims at issue"; and (3) determine "the level of
ordinary skill in the pertinent art."13

   1. Determine The Scope and Content of the Prior Art

   As an initial matter, Office personnel should determine the scope and
content of the relevant prior art. Each reference must qualify as prior
art under 35 U.S.C.    102,14 and should be in the field of applicant's
endeavor, or be reasonably pertinent to the particular problem with
which the inventor was concemed.15

    In the case of a prior art reference disclosing a genus, Office
personnel should make findings as to (1) the structure of the disclosed
prior art genus and that of any expressly described species or subgenus
within the genus; (2) any physical or chemical properties and utilities
disclosed for the genus, as well as any suggested limitations on the
usefulness of the genus, and any problems alleged to be addressed by the
genus; (3) the predictability of the technology; and (4) the number of
species encompassed by the genus taking into consideration all of the
variables possible.

   2. Ascertain The Differences Between the Closest Dis-closed Prior Art
Species or Subgenus of Record and the Claimed Species or Subgenus

   Once the structure of the disclosed prior art genus and that of any
expressly described species or subgenus within the genus are identified,
Office personnel should compare it to the claimed species or subgenus to
determine the differences. Through this comparison, the closest
disclosed species or subgenus in the prior art reference should be
identified and compared to that claimed. Office personnel should make
explicit findings on the similarities and differences between the
closest disclosed prior art species or subgenus of record and the
claimed species or subgenus including findings relating to similarity of
structure, chemical properties and utilities. 16

   3. Determine the Level of Skill in the Art

   Office personnel should evaluate the prior art from the standpoint of
the hypothetical person having ordinary skill in the art at the time the
claimed invention was made.17 In most cases, the only facts of record
pertaining to the level of skill in the art will be found within the
prior art reference. However, any additional evidence presented by
applicant should be evaluated.

   4. Determine Whether One of Ordinary Skill in the Art Would Have Been
Motivated to Select the Claimed Species or Subgenus

   In light of the findings made relating to the three Graham factors,
Office personnel should determine whether one of ordinary skill in the
relevant art would have been motivated to make the claimed invention as
a whole, i.e., to select the claimed species or subgenus from the
disclosed prior art genus.18 To address this key issue, Office personnel
should consider all relevant prior art teachings, focusing on the
following, where present.

   a. Consider the Size of the Genus

   Consider the size of the prior art genus, bearing in mind that size
alone cannot support an obviousness rejection.19 There is no absolute
correlation between the size of the prior art genus and a conclusion of
obviousness.20 Thus, the mere fact that a prior art genus contains a
small number of members does not create a per se rule of obviousness.
Some motivation to select the claimed species or subgenus must be taught
by the prior art.21 However, a genus may be so small that, when
considered in light of the totality of the circumstances, it would
anticipate the claimed species or subgenus. For example, it has been
held that a prior art genus containing only 20 compounds and a limited
number of variations in the generic chemical formula inherently
anticipated a claimed species within the genus because "one skilled in
[the] art would . . . envisage each member" of the genus.22

   b. Consider the Express Teachings

   If the prior art reference expressly teaches a particular reason to
select the claimed species or subgenus, Office personnel should point
out the express disclosure which would have motivated one of ordinary
skill in the art to select the claimed invention.23

   c. Consider the Teachings of Structural Similarity

   Consider any teachings of a "typical," "preferred," or "optimum" species
or subgenus within the disclosed genus. If such a species or subgenus is
structurally similar to that claimed, its disclosure may motivate one of
ordinary skill in the art to choose the claimed species or subgenus from
the genus,24 based on the reasonable expectation that structurally
similar species usually have similar properties.25 The utility of such
properties will normally provide some motivation to make the claimed
species or subgenus.26

   In making an obviousness determination, Office personnel should consider
the number of variables which must be selected or modified, and the
nature and significance of the differences between the prior art and the
claimed invention.27 The closer the physical and chemical similarities
between the claimed species or subgenus and any exemplary species or
subgenus disclosed in the prior art, the greater the expectation that
the claimed subject matter will function in an equivalent manner to the
genus.28

   Similarly, consider any teaching or suggestion in the reference of a
preferred species or subgenus that is significantly different in
structure from the claimed species or subgenus. Such a teaching may
weigh against selecting the claimed species or subgenus and thus against
a determination of obviousness.29 For example, teachings of preferred
species of a complex nature within a disclosed genus may motivate an
artisan of ordinary skill to make similar complex species and thus teach
away from making simple species within the genus.30 Concepts used to
analyze the structural similarity of chemical compounds in other types
of chemical cases are equally useful in analyzing genus-species cases.31
Generally, some teaching of a structural similarity will be necessary to
suggest selection of the claimed species or subgenus.32

   d. Consider the Teachings of Similar Properties or Uses

   Consider the properties and utilities of the structurally similar prior
art species or subgenus. It is the properties and utilities that provide
real world motivation for a person of ordinary skill to make species
structurally similar to those in the prior art.33 Conversely, lack of
any known useful properties weighs against a finding of motivation to
make or select a species or subgenus.34 However, the prior art need not
disclose a newly discovered property in order for there to be a prima
facie case of obviousness.35 If the claimed invention and the
structurally similar prior art species share any useful property, that
will generally be sufficient to motivate an artisan of ordinary skill to
make the claimed species.36 For example, based on a finding that a
tri-ortho ester and a tetra-ortho ester behave similarly in certain
chemical reactions, it has been held that one of ordinary skill in the
relevant art would have been motivated to select either structure.37 In
fact, similar properties may normally be presumed when compounds are
very close in structure.38 Thus, evidence of similar properties or
evidence of any useful properties disclosed in the prior art that would
be expected to be shared by the claimed invention weighs in favor of a
conclusion that the claimed invention would have been obvious.39

   e. Consider the Predictability of the Technology

   Consider the predictability of the technology.40 If the technology is
unpredictable, it is less likely that structurally similar species will
render a claimed species obvious because it may not be reasonable to
infer that they would share similar properties.41 However, obviousness
does not require absolute predictability, only a reasonable expectation
of success, i.e., a reasonable expectation of obtaining similar
properties.42

   f. Consider Any Other Teaching to Support the Selection of the Species
or Subgenus

   The categories of relevant teachings enumerated above are those most
frequently encountered in a genus-species case, but they are not
exclusive. Office personnel should consider the totality of the evidence
in each case. In unusual cases, there may be other relevant teachings
sufficient to support the selection of the species or subgenus and,
therefore, a conclusion of obviousness.

   5. Make Express Fact-Findings And Determine Whether They Support A Prima
Facie Case of Obviousness

   Based on the evidence as a whole,43 Office personnel should make express
fact-findings relating to the Graham factors, focusing primarily on the
prior art teachings discussed above. The fact-findings should
specifically articulate what teachings or suggestions in the prior art
would have motivated one of ordinary skill in the art to select the
claimed species or subgenus.44 Thereafter, it should be determined
whether these findings, considered as a whole, support a prima facie
case that the claimed invention would have been obvious to one of
ordinary skill in the relevant art at the time the invention was made.

   B. Determining Whether Rebuttal Evidence Is Sufficient To Overcome the
Prima Facie Case of Obviousness

   If a prima facie case of obviousness is established, the burden shifts
to the applicant to come forward with arguments and/or evidence to rebut
the prima facie case.45 Rebuttal evidence and arguments can be presented
in the specification,46 by counsel,47 or by way of an affidavit or
declaration under 37 CFR    1.132.48 However, arguments of counsel
cannot take the place of factually supported objective evidence.49

   Office personnel should consider all rebuttal arguments and evidence
presented by applicants.50 Rebuttal evidence may include evidence of
"secondary considerations," such as "commercial success, long felt but
unsolved needs, [and] failure of others,"51 evidence that the claimed
invention yields unexpectedly improved properties or properties not
present in the prior art,52 or evidence that the claimed invention was
copied by others.53 It may also include evidence of the state of the
art, the level of skill in the art, and the beliefs of those skilled in
the art.54 For example, rebuttal evidence may include a showing that the
prior art fails to disclose or render obvious a method for making the
compound, which would preclude a conclusion of obviousness of the
compound.55

   Consideration of rebuttal evidence and arguments requires Office
personnel to weigh the proffered evidence and arguments. Office
personnel should avoid giving evidence no weight, except in rare
circumstances.56 However, to be entitled to substantial weight, the
applicant should establish a nexus between the rebuttal evidence and the
claimed invention,57 i.e., objective evidence of nonobviousness must be
attributable to the claimed invention.58 Additionally, the evidence must
be reasonably commensurate in scope with the claimed invention.59
However, an exemplary showing may be sufficient to establish a
reasonable correlation between the showing and the entire scope of the
claim, when viewed by a skilled artisan.60 On the other hand, evidence
of an unexpected property may not be sufficient regardless of the scope
of the showing.61 Accordingly, each case should be evaluated
individually based on the totality of the circumstances.

   Office personnel should not evaluate rebuttal evidence for its
"knockdown" value against the prima facie case62 or summarily dismiss it
as not compelling or insufficient. If the evidence is deemed
insufficient to rebut the prima facie case of obviousness, Office
personnel should specifically set forth the facts and reasoning that
justify this conclusion.

III. Reconsider All Evidence and Clearly Communicate
     Findings and Conclusions

   A determination under 35 U.S.C.    103 should rest on all the
evidence and should not be influenced by any earlier conclusion.63 Thus,
once the applicant has presented rebuttal evidence, Office personnel
should reconsider any initial obviousness determination in view of the
entire record.64 All the proposed rejections and their bases should be
reviewed to confirm their correctness. Only then should any rejection be
imposed in an Office action. The Office action should clearly
communicate the Office's findings and conclusions, articulating how the
conclusions are supported by the findings.

   Where applicable, the findings should clearly articulate which portions
of the reference support any rejection. Explicit findings on motivation
or suggestion to select the claimed invention should also be articulated
in order to support a 35 U.S.C.    103 ground of rejection.65 Conclusory
statements of similarity or motivation, without any articulated
rationale or evidentiary support, do not constitute sufficient factual
findings.

 VI. Endnotes

1. When evaluating the scope of a claim, every limitation in the claim
must be considered. E.g., In re Ochiai, 71 F.3d 1565, 1572, 37 USPQ2d
1127, 1133 (Fed. Cir. 1995). However, the claimed invention may not be
dissected into discrete elements to be analyzed in isolation, but must
be considered as a whole. E.g., W.L. Gore & Assoc., Inc. v. Garlock,
Inc., 721 F.2d 1540, 1548, 220 USPQ 303, 309 (Fed. Cir. 1983), cert.
denied, 469 U.S. 851 (1984); Jones v. Hardy, 727 F.2d 1524, 1530, 220
USPQ 1021, 1026 (Fed. Cir. 1983) ("treating the advantage as the
invention disregards the statutory requirement that the invention be
viewed `as a whole'").

2. Both claimed and unclaimed aspects of the invention should be
searched if there is a reasonable expectation that the unclaimed aspects
may be later claimed.

3. "The section 103 requirement of unobviousness is no different in
chemical cases than with respect to other categories of patentable
inventions." In re Papesch, 315 F.2d 381, 385, 137 USPQ 43, 47 (CCPA
1963).

4. E.g., In re Dillon, 919 F.2d 688, 692-93, 16 USPQ2d 1897, 1901 (Fed.
Cir. 1990)(in banc).

5. E.g., In re Brouwer, 77 F.3d 422, 425, 37 USPQ2d 1663, 1666 (Fed.
Cir. 1996); In re Ochiai, 71 F.3d 1565, 1572, 37 USPQ2d 1127, 1133 (Fed.
Cir. 1995); In re Baird, 16 F.3d 380, 382, 29 USPQ2d 1550, 1552 (Fed.
Cir. 1994).

6. In re Baird, 16 F.3d 380, 382, 29 USPQ2d 1550, 1552 (Fed. Cir. 1994)
("The fact that a claimed compound may be encompassed by a disclosed
generic formula does not by itself render that compound obvious."); In
re Jones, 958 F.2d 347, 350, 21 USPQ2d 1941, 1943 (Fed. Cir. 1992)
(Federal Circuit has "decline[d] to extract from Merck [& Co. v.
Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.
1989)] the rule that . . . regardless of how broad, a disclosure of a
chemical genus renders obvious any species that happens to fall within
it."). See also In re Deuel, 51 F.3d 1552, 1559, 34 USPQ2d 1210, 1215
(Fed. Cir. 1995).

7. E.g., In re Bell, 991 F.2d 781,783, 26 USPQ2d 1529, 1531 (Fed. Cir.
1993) ("The PTO bears the burden of establishing a case of prima facie
obviousness."); In re Rijckaert, 9 F.3d 1531, 1532, 28 USPQ2d 1955, 1956
(Fed. Cir. 1993); In re Oetiker, 977 F.2d 1443, 1445, 24 USPQ2d 1443,
1444 (Fed. Cir. 1992).
Graham v. John Deere Co., 383 U.S. 1, 17-18 (1966), requires that to
make out a case of obviousness, one must: (1) determine the scope and
contents of the prior art; (2) ascertain the differences between the
prior art and the claims in issue; (3) determine the level of skill in
the pertinent art; and (4) evaluate any evidence of secondary
considerations.

8. E.g., Bell, 991 F.2d at 783-84, 26 USPQ2d at 1531; Rijckaert, 9 F.3d
at 1532, 28 USPQ2d at 1956; Oetiker, 977 F.2d at 1445, 24 USPQ2d at 1444.

9. Id.

10. E.g., In re Brouwer, 77 F.3d 422, 425, 37 USPQ2d 1663, 1666 (Fed.
Cir. 1996) ("[T]he mere possibility that one of the esters or the active
methylene group-containing compounds . . . could be modified or replaced
such that its use would lead to the specific sulfoalkylated resin
recited in claim 8 does not make the process recited in claim 8 obvious
`unless the prior art suggested the desirability of [such a]
modification' or replacement.") (quoting In re Gordon, 733 F.2d 900,
902, 221 USPQ 1125, 1127 (Fed. Cir. 1984); In re Vaeck, 947 F.2d 488,
493, 20 USPQ2d 1438, 1442 (Fed. Cir. 1991) ("[A] proper analysis under
 103 requires, inter alia, consideration of . . . whether the prior art
would have suggested to those of ordinary skill in the art that they
should make the claimed composition or device, or carry out the claimed
process.").

11. The prior art disclosure may be express, implicit, or inherent.
Regardless of the type of disclosure, the prior art must provide some
motivation to one of ordinary skill in the art to make the claimed
invention in order to support a conclusion of obviousness. E.g., Vaeck,
947 F.2d at 493, 20 USPQ2d at 1442 (A proper obviousness analysis
requires consideration of "whether the prior art would also have
revealed that in so making or    carrying out [the claimed invention],
those of ordinary skill would have a reasonable expectation of
success."); In re Dow Chemical Co., 837 F.2d 469, 473, 5 USPQ2d 1529,
1531 (Fed. Cir. 1988) ("The consistent criterion for determination of
obviousness is whether the prior art would have suggested to one of
ordinary skill in the art that this process should be carried out and
would have a reasonable likelihood of success, viewed in the light of
the prior art."); Hodosh v. Block Drug Co., 786 F.2d 1136, 1143 n.5, 229
USPQ 182, 187 n.5 (Fed. Cir. 1986).

12. When evidence of secondary considerations such as unexpected results
is initially before the Office, for example in the specification, that
evidence should be considered in deciding whether there is a prima facie
case of obviousness. The determination as to whether a prima facie case
exists should be made on the full record before the Office at the time
of the determination.

13. Graham v. John Deere, 383 U.S. 1, 17, 148 USPQ 459, 467 (1966).
Accord, e.g., In re Paulsen, 30 F.3d 1475, 1482, 31 USPQ2d 1671, 1676
(Fed. Cir. 1994).

14. E.g., Panduit Corp. v. Dennison Mfg. Co., 810 F.2d 1561, 1568, 1
USPQ2d 1593, 1597 (Fed. Cir. 1987) ("Before answering Graham's `content'
inquiry, it must be known    whether a patent or publication is in the
prior art under 35 U.S.C.    102.").

15. In re Oetiker, 977 F.2d 1443, 1447, 24 USPQ2d 1443, 1445 (Fed. Cir.
1992). Accord, e.g., In re Clay, 966 F.2d 656, 658-59, 23 USPQ2d 1058,
1060 (Fed. Cir. 1992).

16. In Stratoflex, Inc. v. Aeroquip Corp., 713 F.2d 1530, 1537, 218 USPQ
871,877 (Fed. Cir. 1983), the Court noted that "the question under 35
U.S.C.    103 is not whether the differences [between the claimed
invention and the prior art] would have been obvious" but "whether the
claimed invention as a whole would have been obvious." (emphasis in
original).

17. See, Ryko Manufacturing Co. v. Nu-Star Inc., 950 F.2d 714, 718, 21
USPQ2d 1053, 1057 (Fed. Cir. 1991)("The importance of resolving the
level of ordinary skill in the art lies in the necessity of maintaining
objectivity in the obviousness inquiry."); Uniroyal Inc. v. Rudkin-Wiley
Corp., 837 F.2d 1044, 1050, 5 USPQ2d 1434, 1438 (Fed. Cir. 1988)
(evidence must be viewed from position of ordinary skill, not of an
expert).

18. E.g., Ochiai, 71 F.3d at 1569-70, 37 USPQ2d at 1131; Deuel, 51 F.3d
at 1557, 34 USPQ2d at 1214 ("[A] prima facie case of unpatentability
requires that the teachings of the prior art suggest the claimed
compounds to a person of ordinary skill in the art." (emphasis in
original)); Jones, 958 F.2d at 351, 21 USPQ2d at 1943-44 (Fed. Cir.
1992); Dillon, 919 F.2d at 692, 16 USPQ2d at 1901; In re Lalu, 747 F.2d
703, 705, 223 USPQ 1257, 1258 (Fed. Cir. 1984) ("The prior art must
provide one of ordinary skill in the art the motivation to make the
proposed molecular modifications needed to arrive at the    claimed
compound."). See also In re Kemps, 97 F.3d 1427, 1430, 40 USPQ2d 1309,
1311 (Fed. Cir. 1996) (discussing motivation to combine).

19. See, e.g., Baird, 16 F.3d at 383, 29 USPQ2d at 1552 (observing that
"it is not the mere number of compounds in this limited class which is
significant here but, rather, the total    circumstances involved").

20. Id.

21. See, e.g., Deuel, 51 F.3d at 1558-59, 34 USPQ2d at 1215 ("No
particular one of these DNAs can be obvious unless there is something in
the prior art to lead to the particular    DNA and indicate that it
should be prepared."); Baird, 16 F.3d at 382-83, 29 USPQ2d at 1552;
Bell, 991 F.2d at 784, 26 USPQ2d at 1531 ("Absent anything in the cited
prior art suggesting which of the 1036 possible sequences suggested by
Rinderknecht corresponds to the IGF gene, the PTO has not met its burden
of establishing that the prior art would have suggested the claimed
sequences.").

22. In re Petering, 301 F.2d 676, 681, 133 USPQ 275, 280 (CCPA 1962)
(emphasis in original). More specifically, the court in Petering stated:
   A simple calculation will show that, excluding isomerism within
certain of the R groups, the limited class we find in Karrer contains
only 20 compounds. However, we wish to point out that it is not the mere
number of compounds in this limited class which is significant here but,
rather, the total circumstances involved, including such factors as the
limited number of variations for R, only two alternatives for Y and Z,
no alternatives for the other ring positions, and a large unchanging
parent structural nucleus. With these circumstances in mind, it is our
opinion that Karrer has described to those with ordinary skill in this
art each of the various permutations here involved as fully as if he had
drawn each structural formula or had written each name.

Id. (emphasis in original).

Accord In re Schaumann, 572 F.2d 312, 316, 197 USPQ 5, 9 (CCPA 1978)
(prior art genus encompassing claimed species which disclosed preference
for lower alkyl secondary amines and properties possessed by the claimed
compound constituted description of claimed compound for purposes of 35
U.S.C.    102(b)). C.f., In re Ruschig, 343 F.2d 965, 974, 145 USPQ 274,
282 (CCPA 1965) (Rejection of claimed compound in light of prior art
genus based on Petering is not appropriate where the prior art does not
disclose a small recognizable class of compounds with common
properties.).

23. An express teaching may be based on a statement in the prior art
reference such as an art recognized equivalence. For example, see Merck
& Co. v. Biocraft Labs., 874 F.2d 804, 807, 10 USPQ2d 1843, 1846 (Fed.
Cir. 1989) (holding claims directed to diuretic compositions comprising
a specific mixture of amilofide and hydrochlorothiazide were obvious
over a prior art reference expressly teaching that amilofide was a
pyrazinoylguanidine which could be co-administered with potassium
excreting diuretic agents, including hydrochlorothiazide which was a
named example, to produce a diuretic with desirable sodium and potassium
eliminating properties). See also, In re Kemps, 97 F.3d 1427, 1430, 40
USPQ2d 1309, 1312 (Fed. Cir. 1996) (holding there is sufficient
motivation to combine teachings of prior art to achieve claimed
invention where one reference specifically refers to the other).

24. E.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904. See also Deuel, 51
F.3d at 1558, 34 USPQ2d at 1214 ("Structural relationships may provide
the requisite motivation or suggestion to modify known compounds to
obtain new compounds. For example, a prior art compound may suggest its
homologs because homologs often have similar properties and therefore
chemists of ordinary skill would ordinarily contemplate making them to
try to obtain compounds with improved properties.").

25. E.g., Dillon, 919 F.2d at 693, 16 USPQ2d at 1901.

26. See id.

27. E.g., In re Jones, 958 F.2d 347, 350, 21 USPQ2d 1941, 1943 (Fed.
Cir. 1992) (reversing obviousness rejection of novel dicamba salt with
acyclic structure over broad prior art genus encompassing claimed salt,
where disclosed examples of genus were dissimilar in structure, lacking
an ether linkage or being cyclic); In re Susi, 440 F.2d 442, 445, 169
USPQ 423, 425 (CCPA 1971) (the difference from the particularly
preferred subgenus of the prior art was a hydroxyl group, a difference
conceded by applicant "to be of little importance.").
In the area of biotechnology, an exemplified species may differ from a
claimed species by a conservative substitution ("the replacement in a
protein of one amino acid by another, chemically similar, amino acid . .
. [which] is generally expected to lead to either no change or only a
small change in the properties of the protein." Dictionary of
Biochemistry and Molecular Biology 97 (John Wiley & Sons, 2d ed. 1989)).
The effect of a conservative substitution on protein function depends on
the nature of the substitution and its location in the chain. Although
at some locations a conservative substitution may be benign, in some
proteins only one amino acid is allowed at a given position. For
example, the gain or loss of even one methyl group can destabilize the
structure if close packing is required in the interior of domains. James
Darnell et al., Molecular Cell Biology. 51 (2d ed. 1990).

28. E.g., Dillon, 919 F.2d at 696, 16 USPQ2d at 1904 (and cases cited
therein). C.f. Baird, 16 F.3d at 382-83, 29 USPQ2d at 1552 (disclosure
of dissimilar species can provide teaching away).

29. Baird, 16 F.3d at 382-83, 29 USPQ2d at 1552 (reversing obviousness
rejection of species in view of large size of genus and disclosed
"optimum" species which differed greatly from and were more complex than
the claimed species); Jones, 958 F.2d at 350, 21 USPQ2d at 1943
(reversing obviousness rejection of novel dicamba salt with acyclic
structure over broad prior art genus encompassing claimed salt, where
disclosed examples of genus were dissimilar in structure, lacking an
ether linkage or being cyclic).

30. Baird, 16 F.3d at 382, 29 USPQ2d at 1552. See also Jones, 958 F.2d
at 350, 21 USPQ2d at 1943 (disclosed salts of genus held not
sufficiently similar in structure to render claimed species prima facie
obvious).

31. For example, a claimed tetra-orthoester fuel composition was held to
be obvious in light of a prior art tri-orthoester fuel composition based
on their structural and chemical similarity and similar use as fuel
additives. Dillon, 919 F.2d at 692-93, 16 USPQ2d at 1900-02.

Likewise, claims to amitriptyline used as an antidepressant were held
obvious in light of the structural similarity to imipramine, a known
antidepressant prior art compound, where both compounds were tricyclic
dibenzo compounds and differed structurally only in the replacement of
the unsaturated carbon atom in the center ring of amitriptyline with a
nitrogen atom in imipramine. In re Merck & Co., 800 F.2d 1091, 1096-97,
231 USPQ 375, 378-79 (Fed. Cir. 1986).

Other structural similarities have been found to support aprima facie
case of obviousness. E.g., In re May, 574 F.2d 1082, 1093-95, 197 USPQ
601, 610-11 (CCPA 1978) (stereoisomers); In re Wilder, 563 F.2d 457,
460, 195 USPQ 426, 429 (CCPA1977) (adjacent homologs and structural
isomers); In re Hoch, 428 F.2d 1341, 1344, 166 USPQ 406, 409 (CCPA 1970)
(acid and ethyl ester); In re Druey, 319 F.2d 237, 240, 138 USPQ 39, 41
(CCPA 1963)(omission of methyl group from pyrazole ring).

32. Id.

33. Dillon, 919 F.2d at 697, 16 USPQ2d at 1905; In re Stemniski, 444
F.2d 581, 586, 170 USPQ 343, 348 (CCPA 1971).

34. In re Albrecht, 514 F.2d 1389, 1392, 1395-96, 185 USPQ 585, 587, 590
(CCPA 1975) (The prior art compound so irritated the skin that it could
not be regarded as useful for the disclosed anesthetic purpose, and
therefore a person skilled in the art would not have been motivated to
make related compounds.); Stemniski, 444 F.2d at 586, 170 USPQ at 348
(close structural similarity alone is not sufficient to create a prima
facie case of obviousness when the reference compounds lack utility, and
thus there is no motivation to make related compounds.).

35. Dillon, 919 F.2d at 697, 16 USPQ2d at 1904-05 (and cases cited
therein).

36. E.g., id.

37. Id. at 692, 16 USPQ2d at 1900-01.

38. Dillon, 919 F.2d at 693, 696, 16 USPQ2d at 1901, 1904. See also ln
re Grabiak, 769 F.2d 729, 731, 226 USPQ 870, 871 (Fed. Cir. 1985) ("When
chemical compounds have `very close' structural similarities and similar
utilities, without more a prima facie case may be made.").

39. Dillon, 919 F.2d at 697-98, 16 USPQ2d at 1905; In re Wilder, 563
F.2d 457, 461,195 USPQ 426, 430 (CCPA 1977); In re Linter, 458 F.2d
1013, 1016, 173 USPQ 560, 562 (CCPA 1972).

40. See, e.g., Dillon, 919 F. 2d at 692-97, 16 USPQ2d at 1901-05; In re
Grabiak, 769 F.2d 729, 732-33,226 USPQ 870, 872 (Fed. Cir. 1985).

41. See e.g., In re May, 574 F.2d 1082, 1094, 197 USPQ 601, 611 (CCPA
1978) (prima facie obviousness of claimed analgesic compound based on
structurally similar prior art isomer was rebutted with evidence
demonstrating that analgesia and addiction properties could not be
reliably predicted on the basis of chemical structure); In re Schechter,
205 F.2d 185, 191, 98 USPQ 144, 150 (CCPA 1953) (unpredictability in the
insecticide field, with homologs, isomers and analogs of known effective
insecticides having proven ineffective as insecticides, was considered
as a factor weighing against a conclusion of obviousness of the claimed
compounds).

42. See, e.g., In re O'Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673, 1681
(Fed. Cir. 1988).

43. In re Bell, 991 F.2d 781, 784, 26 USPQ2d 1529, 1531 (Fed. Cir. 1993
); In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1057 (Fed. Cir.
1990).

44. Kulling, 897 F.2d at 1149, 14 USPQ2d at 1058; Panduit Corp. v.
Dennison Mfg. Co., 810 F.2d 1561, 1579 n.42, 1 USPQ2d 1593, 1606 n.42
(Fed. Cir. 1987).

45. E.g., Dillon, 919 F.2d at 692, 16 USPQ2d at 1901.

46. In re Soni, 54 F.3d 746, 750, 34 USPQ2d 1684, 1687 (Fed. Cir. 1995).

47. In re Chu, 66 F.3d 292, 299, 36 USPQ2d 1089, 1094-95 (Fed. Cir.
1995).

48. E.g., Soni, 54 F.3d at 750, 34 USPQ2d at 1687; In re Piasecki, 745
F.2d 1468, 1474, 223 USPQ 785, 789-90 (Fed. Cir. 1984).

49. E.g., In re Huang, 100 F.3d 135, 139-40, 40 USPQ2d 1685, 1689 (Fed.
Cir. 1996); In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed.
Cir. 1984).

50. E.g., In re Soni, 54 F.3d 746, 750, 34 USPQ2d 1684, 1687 (Fed. Cir.
1995) (error not to consider evidence presented in the specification).
C.f., In re Alton, 76 F.3d 1168, 37 USPQ2d 1578 (Fed. Cir. 1996) (error
not to consider factual evidence submitted to counter a section 112
rejection); In re Beattie, 974 F.2d 1309, 1313, 24 USPQ2d 1040, 1042-43
(Fed. Cir. 1992) (Office personnel should consider declarations from
those skilled in the art praising the claimed invention and opining that
the art teaches away from the invention.); Piasecki, 745 F.2d at 1472,
223 USPQ at 788 ("[Rebuttal evidence] may    relate to any of the Graham
factors including the so-called secondary considerations.").

51. Graham v. John Deere Co., 383 U.S. at 17, 148 USPQ at 467. See also,
e.g., In re Piasecki, 745 F.2d 1468, 1473, 223 USPQ 785, 788 (Fed. Cir.
1984) (commercial success).

52. Rebuttal evidence may consist of a showing that the claimed compound
possesses unexpected properties. Dillon, 919 F.2d at 692-93, 16 USPQ2d
at 1901. A showing of unexpected results must be based on evidence, not
argument or speculation. In re Mayne, 104 F.3d 1339, 1343-44, 41 USPQ2d
1451, 1455-56 (Fed. Cir. 1997) (conclusory statements that claimed
compound possesses unusually low immune response or unexpected
biological activity that is unsupported by comparative data held
insufficient to overcome prima facie case of obviousness).

53. E.g., In re GPAC, 57 F.3d 1573, 1580, 35 USPQ2d 1116, 1121 (Fed.
Cir. 1995); Hybritech Inc. v. Monoclonal Antibodies, 802 F.2d 1367,
1380, 231 USPQ 81, 90 (Fed. Cir. 1986), cert. denied, 480 U.S. 947
(1987).

54. E.g., In re Oelrich, 579 F.2d 86, 91-92, 198 USPQ 210, 214 (CCPA
1978) (Expert opinions regarding the level of skill in the art were
probative of the nonobviousness of the claimed invention.); Piasecki,
745 F.2d at 1471, 1473-74, 223 USPQ at 790 (Evidence of
non-technological nature is pertinent to the conclusion of obviousness.
The declarations of those skilled in the art regarding the need for the
invention and its reception by the art were improperly discounted by the
Board); Beattie, 974 F.2d at 1313, 24 USPQ2d at 1042-43 (Seven
declarations provided by music teachers opining that the art teaches
away from the claimed invention must be considered, but were not
probative because they did not contain facts and did not deal with the
specific prior art that was the subject of the rejection.).

55. A conclusion of obviousness requires that the reference(s) relied
upon be enabling in that it put the public in possession of the claimed
invention. The court in In re Hoeksema, 399 F.2d 269, 274, 158 USPQ 596,
601 (CCPA 1968), stated:

   Thus, upon careful reconsideration it is our view that if the prior
art of record fails to disclose or render obvious a method for making a
claimed compound, at the time the invention was made, it may not be
legally concluded that the compound itself is in the possession of the
public. [footnote omitted.] In this context, we say that the absence of
a known or obvious process for making the claimed compounds overcomes a
presumption that the compounds are obvious, based on close relationships
between their structures and those of prior art compounds.

   The Hoeksema court further noted that once a prima facie case of
obviousness is made by the PTO through citation of references, the
burden is on the applicant to produce contrary evidence establishing
that the reference being relied on would not enable a skilled artisan to
produce the different compounds claimed. Id. at 274-75, 158 USPQ at 601.
See also Ashland Oil, Inc. v. Delta Resins & Refractories, Inc., 776
F.2d 281, 295, 297, 227 USPQ 657, 666, 667 (Fed. Cir. 1985) (citing
Hoeksema for the proposition above); In re Grose, 592 F.2d 1161, 1168,
201 USPQ 57, 63-64 (CCPA 1979) ("One of the assumptions underlying a
prima facie obviousness rejection based upon a structural relationship
between compounds, such as adjacent homologs, is that a method disclosed
for producing one would provide those skilled in the art with a method
for producing the other . . . Failure of the prior art to disclose or
render obvious a method for making any composition of matter, whether a
compound or a mixture of compounds like a zeolite, precludes a
conclusion that the composition would have been obvious.")

56. Id. See also ln re Alton, 76 F.3d 1168, 1174-75, 37 USPQ2d 1578,
1582-83 (Fed. Cir. 1996).

57. The Federal Circuit has acknowledged that applicant bears the burden
of establishing nexus, stating:

   In the ex parte process of examining a patent application, however,
the PTO lacks the means or resources to gather evidence which supports
or refutes the applicant's assertion that the sales constitute
commercial success. au1,1,C.f. Ex parte Remark, 15 USPQ2d 1498, 1503
([BPAI] 1990) (evidentiary routine of shifting burdens in civil
proceedings inappropriate in ex parte prosecution proceedings because
examiner has no available means for adducing evidence). Consequently,
the PTO must rely upon the applicant to provide hard evidence of
commercial success.

   In re Huang, 100 F.3d 135, 139-40, 40 USPQ2d 1685, 1689 (Fed. Cir.
1996). See also GPAC, 57 F.3d at 1580, 35 USPQ2d at 1121; In re Paulsen,
30 F.3d 1475, 1482, 31 USPQ2d 1671, 1676 (Fed. Cir. 1994).

58. E.g., Paulsen, 30 F.3d at 1482, 31 USPQ2d at 1676. (Evidence of
commercial success of articles not covered by the claims subject to the
35 U.S.C.    103 rejection was not probative of nonobviousness).

59. E.g., In re Kulling, 897 F.2d 1147, 1149, 14 USPQ2d 1056, 1058 (Fed.
Cir. 1990); In re Grasselli, 713 F.2d 731, 743, 218 USPQ 769, 777 (Fed.
Cir. 1983). In re Soni, 54 F.3d 746, 34 USPQ2d 1684 (Fed. Cir. 1995)
does not change this analysis. In Soni, the Court declined to consider
the Office's argument that the evidence of non-obviousness was not
commensurate in scope with the claim because it had not been raised by
the Examiner. 54 F.3d at 751, 34 USPQ2d at 1688.

   When considering whether proffered evidence is commensurate in scope
with the claimed invention, Office personnel should not require the
applicant to show unexpected results over the entire range of properties
possessed by a chemical compound or composition. E.g., In re Chupp, 816
F.2d 643, 646, 2 USPQ2d 1437, 1439 (Fed. Cir. 1987). Evidence that the
compound or composition possesses superior and unexpected properties in
one of a spectrum of common properties can be sufficient to rebut a
prima facie case of obviousness. Id.

   For example, a showing of unexpected results for a single member of a
claimed subgenus,or a narrow portion of a claimed range would be
sufficient to rebut a prima facie case of obviousness if a skilled
artisan "could ascertain a trend in the exemplified data that would
allow him to reasonably extend the probative value thereof." In re
Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980) (Evidence of
the unobviousness of a broad range can be proven by a narrower range
when one skilled in the art could ascertain a trend that would allow him
to reasonably extend the probative value thereof.). But see, Grasselli,
713 F.2d at 743, 218 USPQ at 778 (evidence of superior properties for
sodium containing composition insufficient to establish the
non-obviousness of broad claims for acatalyst with "an alkali metal"
where it was well known in the catalyst art that different alkali metals
were not interchangeable and applicant had shown unexpected results only
for sodium containing materials); In re Greenfield, 571 F.2d 1185, 1189,
197 USPQ 227,230 (CCPA 1978) (evidence of superior properties in one
species insufficient to establish the nonobviousness of a subgenus
containing hundreds of compounds); In re Lindner, 457 F.2d 506, 508, 173
USPQ 356, 358 (CCPA 1972) (one test not sufficient where there was no
adequate basis for concluding the other claimed compounds would behave
the sameway).

60. E.g., Chupp, 816 F.2d at 646, 2 USPQ2d at 1439; Clemens, 622 F.2d at
1036, 206 USPQ at 296.

61. Usually, a showing of unexpected results is sufficient to overcome a
prima facie case of obviousness. See, e.g., In re Albrecht, 514 F.2d
1389, 1396, 185 USPQ 585, 590 (CCPA 1975). However, where the claims are
not limited to a particular use, and where the prior art provides other
motivation to select a particular species or subgenus, a showing of a
new use may not be sufficient to confer patentability. See Dillon, 919
F.2d at 692, 16 USPQ2d at 1900-01.

62. Piasecki, 745 F.2d at 1473, 223 USPQ at 788.

63. E.g., Piasecki, 745 F.2d at 1472-73, 223 USPQ at 788; In re Eli
Lilly & Co., 902 F.2d 943,945, 14 USPQ2d 1741, 1743 (Fed. Cir. 1990).

64. E.g., Piasecki, 745 F.2d at 1472, 223 USPQ at 788; Eli Lilly, 902
F.2d at 945, 14 USPQ2d at 1743.

65. Dillon, 919 F.2d at 693, 16 USPQ2d at 1901; In re Mills, 916 F.2d
680, 683, 16 USPQ2d 1430, 1433 (Fed. Cir. 1990).

August 26, 1998                                             BRUCE A. LEHMAN
                                        Assistant Secretary of Commerce and
                                     Commissioner of Patents and Trademarks