Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Status
Claims 1-48, 52-53, 56-60, and 68-145 were canceled.
Claims 49-51, 54-55, 61-67 and 146-154 are pending.
Claims 67 and 146-153 were withdrawn from further consideration (see below).
Claims 49-51, 54-55, 61-66 and 154 are under consideration.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 5/6/2026 is acknowledged.
Claim(s) 67 and 146-153 were/was withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 5/6/2026.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 12/6/2024 is being considered by the examiner. The signed IDS form is attached with the instant office action.
NPL document number 9 was crossed out and was not considered because a copy of NPL reference number 9 was not submitted.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 49-51, 54-55, 61-66 and 154 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a “written description” rejection.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Regents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members. The Federal Circuit has cautioned that, for claims reciting a genus of antibodies with particular functional properties (e.g., binding to antigen, high affinity, neutralization activity, competing with a reference antibody for binding), “[c]laiming antibodies with specific properties, e.g., an antibody that binds to human TNF-α with A2 specificity, can result in a claim that does not meet written description even if the human TNF-α protein is disclosed because antibodies with those properties have not been adequately described." Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1875, 1877-78 (Fed. Cir. 2011).
“[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species.
The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention. For antibodies, the Federal Circuit has found that possession of a mouse antibody heavy and light chain variable regions provides a structural "stepping stone" to the corresponding chimeric antibody, but not to human antibodies. Centocor, 97 USPQ2d at 1875 (“[T]he application only provides amino acid sequence information (a molecular description of the antibody) for a single mouse variable region, i.e., the variable region that the mouse A2 antibody and the chimeric antibody have in common. However, the mouse variable region sequence does not serve as a stepping stone to identifying a human variable region within the scope of the claims.”). A chimeric antibody shares the full heavy and light chain variable regions with the corresponding mouse antibody; that is, the structure shared between a mouse and chimeric antibody would generally be expected to conserve the antigen binding activity.
Even if a selection procedure is disclosed that was, at the time of the invention, sufficient to enable the skilled artisan to identify antibodies with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad, 94 USPQ2d at 1167; Centocor at 1876 (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”)
Additionally, “An adequate written description must contain enough information about the actual makeup of the claimed products—“a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials,” which may be present in “functional” terminology “when the art has established a correlation between structure and function.” Ariad, 598 F.3d at 1350. But both in this case and in our previous cases, it has been, at the least, hotly disputed that knowledge of the chemical structure of an antigen gives the required kind of structure-identifying information about the corresponding antibodies.” Amgen Inc v. Sanofi 124 USPQ2d 1354, 1361 (Fed. Cir. 2017). “Further, the “newly characterized antigen” test flouts basic legal principles of the written description requirement. Section 112 requires a “written description of the invention.” But this test allows patentees to claim antibodies by describing something that is not the invention, i.e., the antigen. The test thus contradicts the statutory “quid pro quo” of the patent system where “one describes an invention, and, if the law's other requirements are met, one obtains a patent.” Ariad, 598 F.3d at 1345.” Amgen at 1362.
Claim Analysis
Instant claims are drawn to a genetically modified yeast cell comprising: (i) a first heterologous gene encoding an enzyme having glycosidase activity; and (ii) a second heterologous gene encoding an enzyme having O-methyltransferase activity.
Instant specification disclosed 28 glycosidase enzymes (SEQ ID NO: 1-28) which are alpha-L-rhamnosidase or beta-D-glucosidase (page 77, Table 1). However, instant claim 49 recites broad category of “glycosidase” which also encompasses galactosidase, mannosidase, fucosidase, xylosidase, arabinosidase, glucuronidase, sialidase, etc. Only 28 enzymes in two categories of rhamnosidase and glucosidase disclosed by instant specification (Table 1, page 77) cannot be considered as a representative number of species falling within the scope of genus encompassing any possible glycosidase as recited by instant claim 49. Furthermore, as shown by instant Figure 3, while beta-glucosidase AnBgl1 and AoBgl1 release volatile phenol from non-volatile glucoside well, other beta-glucosidases such as PHR691, PHR692 and BcbglA do not release volatile phenol from non-volatile glucoside as much as AnBgl1 and AoBgl1 (instant Figure 3). Because there is a big difference in activity of different beta-glucosidase, one of ordinary skill in the art would not be able to predict that any possible glycosidase encompassed by instant claim 49 will release phenol from glucoside as disclosed by instant specification.
Instant specification disclosed 13 O-methyltransferases (Table 2, page 79) which transfer methyl group to 4-methylguaiacol, guaiacol, o-cresol, m-cresol and p-cresol (Figure 1 and 2). Therefore, O-methyltransferase disclosed by instant specification is a specific category of O-methyltransferase that binds to specific category of phenolic compounds such as 4-methylguaiacol, guaiacol, o-cresol, m-cresol and p-cresol (Figure 1 and 2). However, O-methyltransferase recited by instant claim 49 is so broadly claimed that it can encompass any type of O-methyltransferase that can transfer methyl group to any substrate other than phenolic compounds such as 4-methylguaiacol, guaiacol, o-cresol, m-cresol and p-cresol as disclosed by instant specification. For example, O-methyltransferase recited by instant claim 49 encompasses catechol-O-methyltransferase which is an enzyme responsible for degrading catecholamine neurotransmitters such as dopamine, epinephrine, and norepinephrine, as well as certain hormones. Another possible O-methyltransferase which is encompassed by instant claim 49 can be mRNA cap 2’-O-methyltransferase which is an essential enzyme that adds a methyl group to the 2’-O position of the first transcribed nucleotide adjacent to the 5’ cap of mRNA. Therefore, only 13 O-methyltransferases (Table 2, page 79) which transfer methyl group to 4-methylguaiacol, guaiacol, o-cresol, m-cresol and p-cresol (Figure 1 and 2) disclosed by instant specification cannot be considered as a representative number of species falling within the scope of genus encompassing any possible type of O-methyltransferase as recited by instant claim 49.
Claim 55 defines specific glycosidase disclosed by instant specification, but does not define specific O-methyltransferase. Likewise, claim 62 defines specific O-methyltransferase, but does not define specific glycosidase.
Claims 54 and 61 recite “at least 90% sequence identity” and therefore allow 10% or lower sequence variation in the protein sequence which can occur in active site of the enzyme and deactivate the enzyme. Although these 10% variation occurs outside of active site of the enzyme, some mutations will affect protein folding and kill enzyme activity. Therefore, sequence variation recited by instant claims 54 and 61 encompasses large number of inactive enzymes which cannot convert volatile smoke taint phenols to smoke-free phenolic methyl ethers as disclosed by instant Figure 1. When amino acid variation is introduced into enzyme, one of ordinary skill in the art would not be able to predict that variant enzyme will still have same function as wild type enzyme.
In the field of protein modification technology, a change of a single amino acid residue may change the properties of the protein. Witkowski et al (Biochemistry 38:11643-11650, 1999; PTO-892) teach that one conservative amino acid substitution transforms a B-ketoacyl synthase into a malonyl decarboxylase and completely eliminates B-ketoacyl synthase activity. Seffernick et al., (Bacteriol. 183(8): 2405-2410, 2001; PTO-892) teach that two naturally occurring Pseudomonas enzymes having 98% amino acid sequence identity catalyze two different reactions: deamination and dehalogenation, therefore having different function. It is not always possible to make variants that retain activity if the regions have been altered.
The disclosure therefore does not show that applicant was in possession of the necessary common attributes or features possessed by the members of the claimed genus. Accordingly, the skilled artisan would not recognize that applicants were in possession of the invention as broadly claimed at the time the application was filed.
To overcome this rejection, it is suggested that Applicant cancel claims 50-51, 54-55, 61-62 and add claim limitations of claims 50-51, 55, 62 to independent claim 49 to define specific enzymes disclosed by instant specification.
Closest Prior Art
Closest prior art is Rice et al (US2021/292688; 12/6/2024 IDS). Rice teaches beta-glucosidase expressing yeast for enhanced flavor and aroma in beverage production (title). However, Rice does not teach expression of combination of glycosidase and O-methyltransferase in yeast as claimed by instant claims.
Conclusion
No claim is allowed.
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/CHEOM-GIL CHEONG/Examiner, Art Unit 1645
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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