DETAILED ACTION
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 .
Claims Status
Claims 1-13 is/are currently pending and under examination.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01. Hyperlinks were found on page 9 lines 32-33. Applicant is advised to review the specification in order to ensure that all hyperlinks are identified and appropriately removed.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
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 1-13 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
To satisfy the written description requirement, a patent 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. See, e.g., Moba, B.V, v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention. See, e.g., Pfaff v. Wells Eiees., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641,1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F. 2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991) (one must define a compound by "whatever characteristics sufficiently distinguish it”).
According to the MPEP § 2163, "The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A "representative number of species" means that the species which are adequately described are representative of the entire 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. See AbbVie Deutsch land GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.")."
Claim 7 recites promoters and promoter variants according to claim 1, and claim 11 recites promoters and promoter variants, wherein the promoter variants of claims 1, 7, and 11 are truncations of promoters at least 95% identical to SEQ ID NO:1. Promoter sequences at least 95% identical to SEQ ID NO:1 comprise an enormous genus of nucleotide sequences which is not sufficiently described.
In analyzing whether the written description requirement is met for genus claims, it is first determined whether a representative number of species have been described by their complete structure. In the instant case, the promoters of SEQ ID NO:1 and 6-24 are the only species whose complete structure is disclosed. While the genus encompasses a large number of variants and molecules that have the same activity (i.e., the activity of acting as a promoter) in kind and the genus encompasses a large number of variants and molecules that have a different structure, the specification does not describe the complete structure of a representative number of species of the large genus of promoters having sequences at least 95% identical to SEQ ID NO:1 or functional equivalents thereof. Additionally the specification does not describe the complete structure of a representative number of species of the large genus of modified promoter sequences.
Next, then, it is determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics (i.e. other than nucleotide sequence), specific features and functional attributes that would distinguish different members of the claimed genus. In the instant case, the only other identifying characteristic is that the mutant promoter sequences have the functionality of promoters (pages 5-6) and when truncated, increase expression efficiency (pages 19-20). Such a functional limitation cannot be an identifying characteristic for the claimed diverse genus of molecules since by Applicant’s definition of promoters at least 95% identical to SEQ ID NO:1 or functional equivalent thereof, all members of the claimed genus will have that characteristic. Further, no identifying characteristics of the modified promoters are disclosed.
The inventions of claims 2-6, 8-10, and 12-13 require the use of the inventions of claims 1, 7, and 11 and therefore are likewise rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement.
Response to Arguments
Applicant's arguments filed 03/30/2026 have been fully considered but they are not persuasive.
Applicant argues that a representative number of species of variant promoters at least 95% identical to SEQ ID NO:1 are described in the disclosure, and specifically indicates SEQ ID NO:22 as an example. Applicant indicates page 4 of the specification as providing written description of such variant promoters.
The variant truncated promoter sequences provided are not representative of the full genus of truncated promoters between 95% and 100% identical to SEQ ID NO:1, as they do not encompass modification of merely any nucleotides of SEQ ID NO:1. The specification also does not describe which nucleotides or sequence elements may be modified or must be conserved in order to preserve the desired functionality of the variant promoters (functions indicated, for example, on page 4 of the specification). As it is unclear which sequence elements or nucleotides may be modified or must be conserved, an artisan would not be able to determine that the applicants were in possession of the full scope of the genus of variant promoters, nor that the applicants had described the full scope of said genus.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-7 and 10-13 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Glieder (WO2017109082A1, provided by Applicant with IDS filed 05/08/2023).
Regarding claims 1-6 and 13, Glieder teaches a Komagataella (Pichia) pastoris yeast cell (required by claims 5-6 and 13) comprising a plasmid (required by claim 4) (page 9; claim 1; page 1, Pichia pastoris is also known as Komagataella pastoris), the plasmid comprising an expression cassette comprising a promoter operably linked to a nucleic acid molecule coding for a heterologous or homologous polypeptide (claim 3). Glieder teaches that the orthologous promoter can be a variant of the FMD promoter, comprising between 100 and 1000 nucleotides of the 3’ end of the FMD promoter (page 5). Instant SEQ ID NO:1 is 100% identical to the FMD promoter of SEQ ID NO:1 of Glieder (see alignment below; claim 8). Thus, Glieder teaches truncated FMD promoters comprising a 5’ truncation of 140-523 nucleotides of SEQ ID NO:1 (required by claim 1).
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As the truncated FMD promoter recited in the instant claim 2 is described as promoting increased relative expression efficiency in the instant specification (Figs. 1-7), the truncated FMD promoter taught by Glieder is interpreted to have the same inherent quality of increasing expression efficiency, as the structure is the same (required by claim 2).
Regarding claim 7, Glieder teaches a method for recombinant production of a target polypeptide comprising introducing into a yeast Pichia pastoris cell a vector comprising an expression cassette comprising an orthologous promoter operably linked to a nucleotide sequence encoding the target polypeptide, and comprising culturing the yeast cell to multiply the yeast cell under conditions which promote expression of the target polypeptide (pages 22-23; claims 11-13). The target polypeptide can be GFP or MeHNL (pages 25-27, 32). If the target polypeptide is MeHNL, the method further comprises lysing the cell, collecting the lysate, and testing the function of the MeHNL protein (page 27). Glieder teaches that the orthologous promoter can be a variant of the FMD promoter, comprising between 100 and 1000 nucleotides of the 3’ end of the FMD promoter (page 5). Instant SEQ ID NO:1 is 100% identical to the FMD promoter of SEQ ID NO:1 of Glieder (see alignment below; claim 8). Thus, Glieder teaches truncated FMD promoters comprising a 5’ truncation of 140-523 nucleotides of SEQ ID NO:1.
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Regarding claim 10, Glieder teaches that the yeast cell is a Pichia pastoris cell (pages 22-23).
Regarding claims 11-13, Glieder teaches a method for recombinant production of a target polypeptide comprising introducing into a yeast Pichia pastoris cell a vector comprising an expression cassette comprising an orthologous promoter operably linked to a nucleotide sequence encoding the target polypeptide, and comprising culturing the yeast cell to multiply the yeast cell under conditions which promote expression of the target polypeptide (pages 22-23; claims 11-13). The target polypeptide can be GFP or MeHNL (pages 25-27, 32). If the target polypeptide is MeHNL, the method further comprises lysing the cell, collecting the lysate, and testing the function of the MeHNL protein (page 27). Glieder teaches that the orthologous promoter can be a variant of the FMD promoter, comprising between 100 and 1000 nucleotides of the 3’ end of the FMD promoter (page 5). Instant SEQ ID NO:1 is 100% identical to the FMD promoter of SEQ ID NO:1 of Glieder (see alignment above; claim 8). Thus, Glieder teaches truncated FMD promoters comprising a 5’ truncation of 140-523 nucleotides of SEQ ID NO:1. As the truncated FMD promoter recited in the instant claims 11-12 is described as promoting increased relative expression efficiency in the instant specification (Figs. 1-7), the truncated FMD promoter taught by Glieder is interpreted to have the same inherent quality of increasing expression efficiency, as the structure is the same.
Response to Arguments
Applicant's arguments filed 03/30/2026 have been fully considered but they are not persuasive.
Applicant argues that Vogl (Glieder) merely generally teaches “a promoter having any length between 50 bp and 2000 bp chosen from the nucleotides 1 to 1000 upstream of the 5’ end of the FMD/MOX-encoding gene” (page 12), that “the only examples put into practice by Vogl ‘082 and disclosed in the publication comprise at least 623 bp” and “Vogl ‘082 explicitly refers to promoters having 800 bp as the most preferred embodiment (page 12), and that “promoters having 130 bp or less are non-functional” (including some of the truncated promoters described by the general teaching of Vogl) (pages 12-13).
MPEP 2123 states that “‘The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain.’ In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) (quoting In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)).
A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989). See also Upsher-Smith Labs. v. Pamlab, LLC, 412 F.3d 1319, 1323, 75 USPQ2d 1213, 1215 (Fed. Cir. 2005) (reference disclosing optional inclusion of a particular component teaches compositions that both do and do not contain that component); Celeritas Technologies Ltd. v. Rockwell International Corp., 150 F.3d 1354, 1361, 47 USPQ2d 1516, 1522-23 (Fed. Cir. 1998) (The court held that the prior art anticipated the claims even though it taught away from the claimed invention. ‘The fact that a modem with a single carrier data signal is shown to be less than optimal does not vitiate the fact that it is disclosed.’).”
Though the teaching of Vogl anticipating the instantly claimed truncated promoters is a general teaching, and though the preferred embodiments of Vogl do not anticipate the instantly claimed invention, the broad disclosure of Vogl is relevant as prior art in its entirety. Furthermore, the rejected instant claims 1-6 and 10-13 make no reference to functional requirements, and thus functional attributes need not be considered. Regarding claim 7, while a functional promoter would be required for protein production, the general teaching of Vogl does encompass many species of functional truncated promoters, and thus Vogl does anticipate claim 7.
Withdrawn Rejections - 35 USC § 103
The rejection of claims 1-13 under 35 USC 103 has been withdrawn. Applicant argues that it would not have been obvious to an artisan that P. pastoris cells comprising the truncated FMD promoters taught by Vogl could or should be cultured using a fed-batch process. Applicant argues that “the choice of particular promoters for recombination protein production requires appropriate corresponding cultivation conditions. This is, inter alia, evidenced by Zhang as well as Vogl” (page 17). Applicant argues that the “mere fact that in some instances P. pastoris was described to be cultivated in a fed-batch process cannot be considered as a guidance to apply a fed-batch process for recombinant protein production using a promoter of the present application” (page 17). Applicant notes that Vogl discloses that the promoters taught by Vogl are inducible by derepression (see Abstract; see pages 17-18 of Remarks). The cultivation protocol of Vogl “stand[s] in contrast to the findings of the present application where the concentration of glucose, which is known to be a repressing carbon source in P. pastoris, is not reduced but increased” (page 18). This argument, that the type of cultivation protocol depends upon the selection of promoter and that neither Vogl nor Zhang teach or suggest that a fed-batch process should be used with an FMD promoter, is convincing regarding non-obviousness. A further search of the prior art did not yield art teaching such a combination of promoter and cultivation protocol. As such, it is determined that an artisan would not reasonably assume or predict that a fed-batch process should be used to cultivate P. pastoris cells comprising a coding sequence operatively linked to a truncated FMD promoter or that such a process would provide “conditions suitable for expression of the nucleotide sequence encoding the target polypeptide” (instant claim 8).
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AFRICA M MCLEOD whose telephone number is (703)756-1907. The examiner can normally be reached Mon-Fri 9:00AM-6:00PM EST.
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/AFRICA M MCLEOD/ Examiner, Art Unit 1635
/KIMBERLY CHONG/ Primary Examiner, Art Unit 1636
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