Acceptance of Animal Model is sufficient for Enablement

Ex parte LAWRENCE M. BLATT, HUA TAN and
SCOTT D. SEIWERT
Appeal 2008-6024
Application 11/370,535
Technology Center 1600
Decided: April 27, 2009

1. A method of treating a flavivirus infection in an individual, the method comprising administering to an individual in need thereof an effective amount of an agent that inhibits enzymatic activity of a membrane-bound α-glucosidase, wherein the agent is not an imino sugar.

The Examiner rejected the claims for not being definite, for lacking utility and for not being enabled.

Indefiniteness:
The Examiner alleged that the phrase "wherein the agent is not an imino sugar" was indefinite. Appellants provided exhibits to support their position that imino sugars are recognized by those of skill in the art to be sugars in which the ring oxygen is replaced by a nitrogen atom. The Examiner argued that a compound in a dependent claim "“is arguably ‘an imino sugar’” but the Examiner had no evidence to support this argument. Therefore, the claims were definite.

Utility:
Examiner argued that it lacked utility because treatment included preventing the disease, which is "very unlikely to ever be demonstrated to be possible as a consequence of a medicinal treatment." The Appellants responded by pointing to the definition which included treating symptoms as well. The Board explained, "The Specification defines “treating” as including “completely or partially preventing a disease or symptom thereof” (FF 10); that definition does not require complete, 100% effective prevention of virus infection of any cell of the treated individual. The Examiner has not provided sufficient evidence to support a conclusion that the claimed method would not be useful for “completely or partially preventing a disease or symptom thereof,” as “treating” is defined in the Specification."

Enablement:
The Examiner alleged that the claims were not enabled because it only used an model of flavivirus infection but did not enable treating an HCV infection. The Examiner pointed to a reference that said that the prior art stated, "“validation of the utility of the BVDV surrogate virus model is incomplete, since most of the few drugs that are known to be active against HCV have not been tested against BVDV." However, the rest of the reference stated that although validation was not complete the BVDV model is used by the field and accepted as a model. The Board explained, "Based on that acceptance, persons of skill in the art would expect that a drug that is shown to be effective against BVDV would reasonably be expected to also be effective against HCV."

The Examiner also objected to another claim that used the phrase "and at least one additional therapeutic agent" because it could be an infinite number of agents. The Examiner explained "“reliance on the term ‘at least one’ extends the possible number of ‘additional therapeutic agents’ to infinity, a circumstance which is clearly not enabled by the instant disclosure." The Board reversed finding that this is not sufficient evidence to show that it is not enabled and that the Examiner has not shown that it would require undue experimentation.

The Board Explained:

"The Examiner has provided no reasonable basis for concluding that a person of ordinary skill in the art could not have practiced the method of claim 6 without undue experimentation. The Examiner has posited a potentially inoperative embodiment encompassed by the claim but that by itself does not show nonenablement without evidence that the number of inoperative embodiments is so large that distinguishing between operative and inoperative embodiments would itself require undue experimentation. No such evidence has been presented."

All rejections were reversed.

Full opinion can be found here.

A list that fails to disclose a species can anticipates the species if that species is "at once envisaged"?

IN RE MARTIN GLEAVE (Fed. Cir. March 26, 2009)
Claims at Issue:

1. A bispecific antisense oligodeoxynucleotide, wherein substantially all of the oligodeoxynucleotide is complementary to a portion of a gene encoding human IGFBP-2 and substantially all of the oligodeoxynucleotide is also complementary to a gene encoding human IGFBP-5, and wherein the oligodeoxynucleotide is of sufficient length to act as an antisense inhibitor of human IGFBP-2 and human IGFBP-5.

4. The antisense oligodeoxynucleotide according to claim 1, wherein the oligodeoxynucleotide consists essentially of a series of bases as set forth in any of Seq. ID. Nos. 3 through 7. [Those sequences range from eighteen to twenty-two DNA bases in length and SEQ ID NO: 5 is a 20mer.]

The claims were rejected as anticipated by Wraight.

"In Wraight, the applicants listed every fifteen-base-long sense oligodeoxynucleotide in the IGFBP-2 gene. The list includes more than 1400 sequences. Wraight also disclosed the general concepts that antisense oligonucleotides are preferably between fifteen and twenty-five bases in length, and that some antisense oligonucleotides may be bispecific (i.e., capable of inhibiting “an IGFBP such as IGFBP-2 and/or IGFBP-3”). Finally, Wraight states that “[a]ntisense oligonucleotides to IGFBP-2 may be selected from molecules capable of interacting with one or more” of the sense oligonucleotides described in the long list. "

The court explained what constitutes a proper 102(b) rejection

A reference is anticipatory under § 102(b) when it satisfies particular requirements. First, the reference must disclose each and every element of the claimed invention, whether it does so explicitly or inherently. Eli Lilly & Co. v. Zenith Goldline Pharms., Inc., 471 F.3d 1369, 1375 (Fed. Cir. 2006). While those elements must be “arranged or
combined in the same way as in the claim,” Net MoneyIN, Inc. v. VeriSign, Inc., 545 F.3d 1359, 1370 (Fed. Cir. 2008), the reference need not satisfy an ipsissimis , 545 F.3d 1312, 1314 (Fed. Cir. 2008); , 339 F.3d 1373, 1380–81 (Fed. Cir. 2003); verbis test, In re Bond, 910 F.2d 831, 832–33 (Fed. Cir. 1990). Second, the reference must “enable one of ordinary skill in the art to make the invention without undue experimentation.” Impax Labs., Inc. v. Aventis Pharms. Inc.see In re LeGrice, 301 F.2d 929, 940–44 (CCPA 1962). As long as the reference discloses all of the claim limitations and enables the “subject matter that falls within the scope of the claims at issue,” the reference anticipates—no “actual creation or reduction to practice” is required. Schering Corp. v. Geneva Pharms., Inc.see In re Donohue, 766 F.2d 531, 533 (Fed. Cir. 1985).

Gleave (the appellant) argued that

“Wraight does not describe any particular individual antisense species,” because Wraight merely gives the public “ink, formed into strings of letters, without inventive thought and without placing the public in possession of anything new. There is no guidance to make particular selections, and no understanding of which of the targets would be useful, and what the properties of the related antisense would be.”

The Federal Circuit, however, stated that the enablement requirement of 102 is not how to use for a composition, just how to make.

"A thorough reading of our case law, however, makes clear that a reference need disclose no independent use or utility to anticipate a claim under § 102. E.g., Novo Nordisk Pharms., Inc. v. Bio-Tech. Gen. Corp., 424 F.3d 1347, 1355 (Fed. Cir. 2005)"

The court explained that any confusion about utility or use comes from case law related to method claims. The court explained to enable a method you have to be able to use it not make it.

"Gleave’s claims are to compositions of matter—oligonucleotides—and therefore a reference satisfies the enablement requirement of § 102(b) by showing that one of skill in the art would know how to make the relevant sequences disclosed in Wraight. "…"Thus, the fact that Wraight provides “no understanding of which of the targets would be useful” is of no import, because Gleave admits that it is well within the skill of an ordinary person in the art to make any oligodeoxynucleotide sequence. See Appellant’s Br. 10. As such, Wraight is an enabling disclosure sufficient to anticipate Gleave’s invention under § 102(b). "

Applicant also argued that the prior art did not teach any oligo with antisense activity. The appellant's lawyer even admitted this even with the following phrase "sufficient length to act as an antisense inhibitor " in the claim. Therefore, they viewed the antisense inhibitor limitation as an intended use and not relevant for 102 analysis. "Certainly where the claims themselves do not require a particular activity, we have no call to require something more from the anticipating reference. "

Gleave argued that a long list should not be anticipatory and should be treated more like a generic statement. Court explained that lists and generic terms have always been treated differently except when a genus can anticipate a species when:

compounds that falls within the genus is so limited that a person of ordinary skill in the art can “at once envisage each member of this limited class.” Eli
Lilly, 471 F.3d at 1376. In that limited circumstance, a reference describing the genus anticipates every species within the genus. See Perricone, 432 F.3d at 1377.

The court explained this argument regarding the two types of claims fails for two reasons:

First, Wraight expressly lists every possible fifteen-base-long oligodeoxynucleotide sequence in IGFBP-2, and under our precedent, this list anticipates Gleave’s claims. Second, even if we were to accept Gleave’s invitation to treat Wraight as equivalent to the statement that one “could make antisense that targets IGFBP-2,”4 which we decline to do, a person of ordinary skill in the art equipped with an IGFBP sequence is admittedly capable of envisioning how to make any antisense sequence. Thus, even
if we were to adopt Gleave’s policy position, Gleave’s claims would not be entitled to a patent over Wraight.

The explained that at most Gleave has invented a method of use not a claim for the composition itself.

What wasn't explained is why the claims to the specific sequences were anticipated since only 15mers were disclosed in Wraight and those in claim 4 were from 18-22 and the elected species was a 20mer. The only explanation that I can think of is that Wraigh said an antisense oligo that is from 15-25 can be made and therefore all oligos 18-22 could be at once envisaged? Thoughts?

The full opinion can be found here.

X-ray Powder Diffraction Pattern is Relevant for Obviousness Analysis regardless of whether or not the compound has unexpected properties. (BPAI)

Ex parte MANNE SATYANARAYANA REDDY et al (BPAI)
Appeal 2008-4197
Application 10/651,306
Technology Center 1600
Decided: March 18, 2009

Claims at issue:
1. A hydrous compound of the formula …

42. Hydrous (S)-5-methoxy-2-[[4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole magnesium in the form of an amorphous solid made by a process comprising:…

44. A solid pharmaceutical composition comprising a hydrous (S)-5-methoxy-2-[[4-methoxy-3,5-dimethyl-2-pyridinyl)methyl]sulfinyl]-1H-benzimidazole magnesium in the form of an amorphous solid, wherein the esomeprazole magnesium has substantially the same X-ray powder diffraction pattern as shown in Figure 1, and a pharmaceutically acceptable carrier.

45. A method for reducing gastric acid secretion in a subject which comprises administering to the subject a solid pharmaceutical composition comprising an amount of the compound of claim 1 effective to reduce gastric acid secretion by said subject.

The Examiner rejected claim 42 under 112, second paragraph for the use of product-by-process claim language. The Examiner argued that since they could describe the product as evidence by claim 1, product by process claims are improper. The Board reversed citing, SmithKline Beecham Corp. v. Apotex Corp., 439 F.3d 1312, 1315 (Fed. Cir. 2006), citing that rule the Examiner was using is not the correct standard.

The Examiner rejected claims 44 and 45 for lack of written description and enablement. The Board emphasized that written description and enablement are distinct and noted that the Examiner did not provide any argument regarding written description and therefore reversed that rejection. With regards to enablement the Examiner was concerned that the form claimed could transform in the solid form and therefore the claim was not enabled for some reason. Appellants pointed out that if there was a transformation that changed the x-ray diffraction pattern then it would be outside the scope of the claim and thus not part of the claim. Appellants also supplied evidence stating that conversion from one form to another is "so slow as to be negligible" and that even if it was converted it does not impact the activity of the compound. Examiner never responded to these arguments and therefore they reversed.

The claims were also rejected as obvious. The Examiner cited references describing related compounds that disclosed that some drugs may exist in amorphous forms but do not refer to the claimed compound. The Examiner also stated that an X-ray diffraction pattern although a property is not enough to overcome obviousness unless the X-ray form has an advantage or unexpected results. The prior art references failed to show any compound with a similar X-ray powder diffraction pattern. Therefore, the Board found that the claims were not obvious and reversed the Examiner.

Case can be found here.

BPAI holds that "paving the way" to the claimed invention does not enable the entire scope

Ex parte WENDELL LIM, JOHN DUEBER, and BRIAN YEH (BPAI)
Appeal 2008-3676
Application 10/613,380
Technology Center 1600
Decided: March 18, 2009

The claim at issue:

1. An autoregulated fusion protein comprising an output domain and a plurality of input domains, wherein at least one of the input domains is heterologous to the output domain, and the input domains interact with each other to allosterically and external ligand-dependently regulate the output domain.

The Applicants provided one working example and described how one of skill in the art would use their techniques to screen other "output domain" (catalytic domains) and "input domain" (regulatory domains, i.e. SH3 domain) to create the autoregulated fusion protein. The Examiner, which the Board agreed with, found that the specification did not provide a person to "predictably produce" a desired fusion protein and that an "extremely large amount of experimentation would be required." The Board instead characterized the specification as "an interesting avenue of further research." The Board explained:

They, may have even paved the way for further research
(see e.g., App. Br. 6). What they have not done is provide an enabling
description of the claimed invention that would allow a person of ordinary skill
in the art to practice the claimed invention without undue
experimentation. Other than the recommendation that one do the screens and
figure it out for yourself, Appellants have provided no guidance on how to
successfully select the appropriate plurality of input domains that can be
fused, with or without a linker, to an output domain to successfully obtain a
fusion protein with the properties one would desire.

Applicants had submitted a declaration stating that “[t]hose skilled in the art have recognized that the invention is not limited to a single embodiment, but that Applicants’ teachings ‘…pave the way for creating new signal-response elements by protein design[’]” The Board found this unconvincing because "providing an interesting avenue for further research (e.g., paving the way) is not the same as providing a disclosure that enables a person of ordinary skill in the art to practice the claimed invention without undue experimentation."

Case can be found here.

"Conclusive Evidence" showing possession is not required for Written Description; "Mere Assertions" not enough to show lack of enablement (BPAI)

Ex parte SAMUEL LOCKWOOD et al. (BPAI)
Appeal 2008-5693
Application 10/793,676
Technology Center 1600
Decided: March 2, 2009

Claim:
A method of reducing C-reactive protein (CRP) levels in a subject comprising administering to a subject who would benefit from such treatment, an effective amount of a pharmaceutically acceptable formulation to reduce the level of circulating CRP in the subject, said pharmaceutically acceptable formulation comprising a non naturally occurring carotenoid analog or derivative; wherein the synthetic carotenoid analog or derivative has the structure …

The Examiner rejected the claims as lacking written description and lacking enablement. The Examiner alleged that the specification "fails to disclose any treatable diseases caused by increased C-reactive protein (CRP), and how reducing CRP is the same as treating the diseases” and characterized the claims as reach through claims, which according to the Examiner are unpatentable. Applicants countered showing that there is a correlation with CRP and certain known diseases.

The Board stated reversed the Examiner. The Board found that the "specification provides direct descriptive support of an association between many ischemic disease states and reperfusion injury (FF 1-2). The Specification directly teaches that levels of C-reactive protein are associated with reperfusion injury and that treatment of these conditions with carotenoids “is expected to inhibit and/or ameliorate . . . disease conditions” (Spec. 7, ll. 2-5; FF 3-4). The Specification also teaches possession of a large number of specific carotenoids (FF 5)." The Examiner had argued that there was no "no conclusive evidence that reduction of circulating CRP is ‘a powerful anti-inflammatory therapeutic modality’ and/or ‘a strong therapeutic modality’” The Board held that for written description this standard is incorrect you only have to show possession of the invention, not conclusive evidence of a link.

The claims were also rejected as being non-enabled. The Examiner did not provide any evidence other than opinion that the claims were not enabled. The Examiner seemed to rely upon the step of detecting and diagnosing CRP to perform the claim. The Board noted that this is routine and not undue. The Examiner also argued that it is not known all diseases arising from CRP are known. The Board held that it is not a requirement and there can be some inoperative embodiments. The Examiner argued that there could be some mutations that cause constituve expression of CRP rather than heart injury. But this argument was not supported by any evidence just Examiner opinion.

The Board Concluded: "The Examiner has not provided the required evidence or scientific reasoning to show that one of ordinary skill in the art would find that reduction of CRP levels in a patient would have required “undue experimentation”. The Examiner's mere assertions to that effect are not sufficient for establishing a prima facie case of lack of enablement. Balancing the factors in the Wands analysis, upon which the rejection is based, demonstrates that there is no prima facie case of lack of enablement.

The claims were rejected for being indefinite but the Examiner failed to say why and thus the rejection was reversed. The claims were also rejected for containing new matter because an R group was not in the specification. This was a new ground of rejection and was remanded to the Examiner for further prosecution.

Case can be found here

Enablement requires both how to use and how to make-BPAI

Ex parte SAMUELSON (BPAI)
Appeal 2008-5927
Application 10/958,452
Technology Center 1600
Decided: February 10, 2009

16. A method of modulating the conformation of DNA (deoxyribonucleotides) double helix which is bound to polyaniline in a complex, comprising changing the oxidation state of the polyaniline.

The claim was rejected for not being enabled. The Examiner did not reject it on how to make but rather on "how to use." The Examiner found that it would require undue experimentation to use the invention. The Board looked to the specification for the uses and agreed. Therefore, although the "use" was not in the claim it was read into the claim for purposes of determining whether the claim was enabled.

The Examiner reasoned "the specification does not provide any example or other form of enabling guidance as to how the changes in oxidation state of polyaniline-dsDNA is to be used in a method that has utility, and no declaration has been filed which would show that appellants have been able to use the invention in the manner disclosed, using the guidance provided. This lack of showing, and the teachings of Zhang et al., some 9 years post effective filing date, all point to the instant disclosure as not being enabling for the claimed invention."

The Board summarized the law as follows:
The Court has explained that “‘the how to use prong of section 112 incorporates as a matter of law the requirement of 35 U.S.C. § 101 that the specification disclose as a matter of fact a practical utility for the invention.’” In re Cortright, 165 F.3d 1353, 1356 (Fed. Cir. 1999), quoting In re Ziegler, 992 F.2d 1197, 1200 (Fed. Cir. 1993). “Patent protection is granted in return for an enabling disclosure . . . , not for vague intimations of general ideas that may or may not be workable.”

The Board held: Balancing the Wands factors, we agree with the Examiner that undue experimentation would have been required to use the claimed invention. With a Specification that only teaches methods of making the DNA-polyaniline complex (FF 2-8), with no guidance as to how modulating the DNA-polyaniline complexes results in a practical, real world use, such as use as a biosensor (FF 9-11), the significant experimentation required for use the polyaniline-DNA complex in the claimed method, and the unpredictibilty of the prior art, we conclude that it would require an undue amount of experimentation to use the polyaniline-DNA complex in a method of modulating conformation as set forth in the claim 16.

Case can be found here

Enablement requires more than "mere plausibility'--BPAI

Ex parte JACQUES DUMAS (Bayer Corporation)
Appeal 2008-3379
Application 09/838,286
Technology Center 1600
Decided: February 10, 2009

Claim at issue:
50. A method of treating a disease mediated by p38 within a host, said method comprising administering to said host a compound of Formula I.

The Examiner rejected claims 50 and 52-56 under 35 U.S.C. § 112, first paragraph as enabled for treating rheumatoid arthritis, osteoarthritis and septic arthritis with the compound of formula I but not reasonably enabled for “a method of treating a disease mediated by p38 within a host” with the compound of formula I.

Appellants contend “[n]o evidence has been presented which even suggests that any compounds of this invention, as inhibitors of p38, would not be effective in treating the diseases defined by the functional language. Furthermore, no evidence has been presented of the ‘undue experimentation,’ allegedly necessary to practice the invention commensurate in scope with the claims” (App. Br. 3). Appellants contend that “one of ordinary skill in the art, by performing the same or similar tests, can, by routine experimentation, determine the activity levels of each of the claimed compounds in treating various p38 mediated diseases”

The Board found that "The art cited by the Examiner provides extensive evidence of the unpredictability of p38 inhibitors in treating diseases, including diseases expressly listed in the Specification" and affirmed the holding that the claims were not enabled for the entire scope. The Board affirmed the Examiner stating: "The Specification only teaches methods of making the compounds of formula I with no teaching or examples of specific diseases on which the compounds are predicted to function (FF 1-4)." The found that there was significant unpredictability in the art.

“If mere plausibility were the test for enablement under section 112, applicants would obtain patent rights to ‘inventions’ consisting of little more than respectable guesses as to the likelihood of their success. When one of the guesses later proved true, the ‘inventor’ would be rewarded the spoils instead of the party who demonstrated that the method actually worked. That scenario is not consistent with the statutory requirement that the inventor enable an invention rather than merely proposing an unproved hypothesis.” Rasmusson v. SmithKline Beecham Corp., 413 F.3d 1318. The Appellants argued that they did not have to enable every species but the Board stated "while a claim may encompass some inoperable subject matter, it must encompass some operable matter."--Almost seeming to indicate that any method isn't enabled but they did defer to the Examiner on the 3 conditions that are mentioned above.

Case can be found here

Ex parte GERHARD JAEHNE

Ex parte GERHARD JAEHNE 

Appeal 2008-4548 

Application 10/463,789 

Technology Center 1600 

BPAI

__________ 

Decided:1 February 2, 2009 

This case had claims to a pharmaceutical composition and a method of using.  The Examiner rejected the claims for lack of written description and not being enabled.  The BPAI reversed the enablement rejection because the Examiner only found that the claim was broad but did not find that any of the other Wands factors tended toward a showing of lack of enablement.  The written description was satisfied because although there was no ipsis verbis support one of skill in the art would have recognized possession because the term that was being used was inherently needed for the composition to even exist.  "The Specification "provides adequate direction which reasonably leads persons skilled in the art to the later claimed compound."

Case can be found here: