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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 2/12/2026 has been entered.
Status of Application, Amendments, And/Or Claims
The Applicants amendments/remarks received 2/12/2026 are acknowledged. Claim 1 is amended; claims 2 and 13-31 are canceled; no claims are withdrawn; claims 1 and 3-12 are pending and have been examined on the merits.
Information Disclosure Statement
The information disclosure statements submitted on 10/21/2025 and 3/10/2026 have been considered by the examiner.
Claim Rejections - 35 USC § 103
The rejection of claims 1, 6-9 and 11 under 35 U.S.C. § 103(a) over Lippmeier et al., US 2011/0195448 (U.S. Patent Application Publications cite 3, IDS, 8/1/2022; herein “Lippmeier”) as set forth at pp. 3-6 of the previous Office Action is withdrawn in view of the amendment of the claims.
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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1, 3-4, 6-9 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Lippmeier et al., US 2011/0195448 (U.S. Patent Application Publications cite 3, IDS, 8/1/2022; herein “Lippmeier”) in light of Diao et al., US 2017/0298394 (cite A, attached PTO-892; herein “Diao”).
Lippmeier is drawn to methods for producing recombinant thraustochytrids that grow on xylose, i.e., a method of making thraustochytrid microorganisms with increased xylose consumption (Abst.). Lippmeier teaches embodiments wherein the thraustochytrid comprises nucleic acid molecules encoding zero or more polypeptides associated with xylose import, two or more polypeptides associated with conversion of xylose to xylulose, and one or more polypeptides associated with phosphorylation of xylulose and embodiments wherein the thraustochytrid comprises nucleic acid molecules encoding zero or more polypeptides associated with xylose import, one or more polypeptides associated with conversion of xylose to xylulose, and two or more polypeptides associated with phosphorylation of xylulose [0053] wherein the polypeptides associated with conversion of xylose to xylulose can comprise a heterologous xylose isomerase and wherein the polypeptides associated with phosphorylation of xylulose can comprise a heterologous xylulose kinase [0052]; hence, a person of ordinary skill in the art at the time of filing would have found it obvious for the method of Lippmeier to comprise providing xylose-consuming thraustochytrid microorganisms comprising two or more copies of a nucleic acid sequence encoding xylose isomerase and two or more copies of a nucleic acid sequence encoding a xylulose kinase. Lippmeier teaches that the recombinant thraustochytrids comprising heterologous xylose isomerase and heterologous xylulose kinase are further improved for growth on xylose, i.e., have increased xylose consumption, by serially culturing the recombinant thraustochytrids in xylose-containing liquid media for 19 rounds (Example 4, [0121-123]; Table 2). Lippmeier teaches [0121] that the liquid xylose-containing medium is xylose-SSFM which comprises 50 g/L xylose, i.e., 5 % xylose weight/volume [0114-115]. Lippmeier does not specify the length of culture for each round of selection in xylose-containing media; however, Lippmeier discloses that the recombinant thraustochytrids are grown in liquid media for 3 days for the expression of the heterologous proteins encoded by the nucleic acids [0120]. Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method of producing thraustochytrid microorganisms with increased xylose consumption made obvious by Lippmeier comprising providing xylose-consuming thraustochytrid microorganisms comprising two or more copies of a nucleic acid sequence encoding xylose isomerase and two or more copies of a nucleic acid sequence encoding a xylulose kinase; culturing the thraustochytrid microorganisms in a first culture medium comprising xylose for 3 days; harvesting a portion of the thraustochytrid microorganisms from the first culture medium after culture; culturing the harvested portion of thraustochytrid microorganisms in a second culture medium comprising xylose for 3 days; harvesting a portion of the thraustochytrid microorganisms from the second culture medium after culture; repeating the culturing and harvesting at least two times in a third culture medium and a fourth culture medium; isolating the harvested thraustochytrid microorganisms wherein the isolated thraustochytrid microorganisms have increased xylose consumption rates compared to control xylose-consuming thraustochytrid microorganisms, wherein the thraustochytrid microorganisms are cultured for 3 days in one or more of the culturing steps, wherein the culturing and harvesting steps are repeated 19 times in 19 culture medias and wherein the media in the culturing steps comprises 50 g/L xylose.
Lippmeier teaches that the purpose for producing recombinant thraustochytrids which can consume xylose is to provide recombinant thraustochytrids which can grow on alternative carbon sources such as hemicellulosic materials [0010-13], and discloses embodiments wherein the recombinant thraustochytrids are cultured in culture medium comprising hemicellulose-containing feedstock, such as corn stover [0061]. Diao is cited as evidence that corn stover hydrolysate comprises 44.9 g/L xylose and 63.2 g/L glucose, i.e., a corn stover hemicellulose-containing feedstock comprises both xylose and glucose. Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Lippmeier wherein the xylose source also comprises glucose because Lippmeier teaches that the carbon source in the culture medium can be hemicellulosic feedstock, such as corn stover, which comprise both xylose and glucose, and because Lippmeier teaches that the ultimate aim is to provide recombinant thraustochytrids which can grow on alternative carbon sources such as hemicellulosic materials; therefore, claims 1, 3-4, 6-9 and 11 are prima facie obvious.
Response to Arguments
Applicant's arguments filed 2/12/2026 have been fully considered but they are not persuasive. Regarding the rejection of claims 1, 6-9, and 11 under 35 U.S.C. 103 over Lippmeier, Applicant argues (Remarks, 2/12/2026, p. 5) that incorporation of the limitation “wherein one or more of the culture media further comprises glucose” into claim 1 renders claim 1 and all dependent claims non-obvious over Lippmeier.
This is unpersuasive because Lippmeier teaches that the culture medium can comprise a hemicellulose-containing feedstock, such as corn stover [0061] and evidentiary reference Diao discloses that corn stover feedstock comprises glucose as well as xylose (see rejection set forth above); hence, a person of ordinary skill in the art at the time of filing would have found it obvious for the culture medium in the method made obvious by Lippmeier to comprise glucose as well as xylose because Lippmeier teaches that the culture medium can comprise corn stover hemicellulosic feedstock which comprises xylose and glucose.
Applicant further argues that Lippmeier does not explicitly state that the time of culture for the 19 rounds of selection in the method made obvious by Lippmeier is 3 days. The rejection set forth above makes it clear that a person of ordinary skill in the art at the time of filing would have found it obvious for the days of culture for each of the rounds of selection to be around 3 days of culture because Lippmeier teaches that recombinant thraustochytrids are grown in liquid media for 3 days for the expression of the heterologous proteins encoded by the nucleic acids and because the recombinant thraustochytrids in the selection process made obvious by Lippmeier comprise nucleic acids encoding xylose isomerase and xylulose kinase, i.e., they are recombinant thraustochytrids requiring the expression of heterologous proteins encoded by the nucleic acids; thus, a person of ordinary skill in the art at the time of filing would have found it obvious to culture the recombinant thraustochytrids for about 3 days in each round of the selection process because Lippmeier demonstrates that 3 days in culture is sufficient for the expression of the heterologous proteins, i.e., xylose isomerase and xylulose kinase, encoded by the nucleic acids.
Despite this reasoning being set forth in the rejection in the previous Office action, Applicant does not provide any further argument as to why culturing for 3 days at each round of the selection process would somehow be NON-OBVIOUS over the prior art.
Hence, Applicant’s arguments are unpersuasive that instant claims 1, 3-4, 6-9 and 11 are not prima facie obvious over Lippmeier in light of Diao.
Claims 1, 3-9 and 11 are rejected under 35 U.S.C. 103 as being unpatentable over Lippmeier et al., US 2011/0195448 (U.S. Patent Application Publications cite 3, IDS, 8/1/2022; herein “Lippmeier”) in view of Van Maris et al., US 2020/0377846 (cite A, PTO-892, 9/6/2024; herein “Van Maris”).
The method made obvious by Lippmeier can comprise performing the selection in media comprising xylose and glucose, as discussed above, but Lippmeier does not disclose a concentration ratio of glucose to xylose in the culture medium; however, a person of ordinary skill in the art at the time of filing would have found it obvious to perform the selection in media comprising a concentration ratio of glucose to xylose of 2:2 to 2:5 in view of Van Maris.
Van Maris also teaches a directed evolution method for producing microorganisms which can consume xylose as well as glucose (Abst.; Fig. 2) wherein the microorganisms comprise one or more heterologous genes encoding an enzyme of a pentose metabolic pathway comprising a gene encoding a xylose isomerase and a gene encoding a xylulose kinase [0040] wherein the first culture comprises 2% xylose and 0.1% glucose; the second culture comprises 2% xylose and 0.2% glucose; the third culture comprises 2% xylose and 0.5% glucose; the fourth through eighth culture comprises 2% xylose and 1% glucose; the ninth and tenth cultures comprise 2% xylose and 1.5% glucose and the eleventh through thirteenth cultures comprise 2% xylose and 2% glucose (Fig. 2).
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Lippmeier wherein the culture mediums for the directed evolution protocol comprise a concentration ratio of glucose to xylose of 2:2 to 2:5 for the 4th through 13th cultures because 2% xylose and 1% glucose is 2:4 glucose:xylose; 2% xylose and 1.5% glucose is 2:2.67 glucose:xylose and 2% xylose and 2% glucose is 2:2 glucose:xylose, because Van Maris demonstrates that culturing with both glucose and xylose wherein the glucose concentration gradually increases with the rounds of selection produces microorganisms which can consume both xylose and glucose; therefore, claim 5 is prima facie obvious.
Response to Arguments
Regarding the rejection of claims 1-9 and 11 under 35 U.S.C. § 103 over Lippmeier in view of Van Maris, Applicant notes (pp. 5-6) “Applicant notes Van Maris is directed to producing a genetically modified S. cerevisiae yeast to increase bioethanol production. Lippmeier is directed to a method of producing engineered microorganisms to express polypeptides associated with xylose usage.” Applicant does explain the purpose of this “note”; however, it should be further noted that Van Maris is drawn to a directed evolution method for producing microorganisms which consume xylose as well as glucose (Abst.; Fig. 2) wherein the microorganisms comprise one or more heterologous genes encoding an enzyme of a pentose metabolic pathway comprising a gene encoding a xylose isomerase and a gene encoding a xylulose kinase [0040] wherein the first culture comprises 2% xylose and 0.1% glucose; the second culture comprises 2% xylose and 0.2% glucose; the third culture comprises 2% xylose and 0.5% glucose; the fourth through eighth culture comprises 2% xylose and 1% glucose; the ninth and tenth cultures comprise 2% xylose and 1.5% glucose and the eleventh through thirteenth cultures comprise 2% xylose and 2% glucose (Fig. 2). Hence, Van Maris is clearly drawn to producing microorganisms with increased xylose consumption by a directed evolution method wherein the microorganisms express heterologous xylose isomerase and xylulose kinase genes in a method comprising serially culturing the microorganisms in culture media with xylose and glucose wherein the glucose concentration increases with later rounds of the culturing and harvesting process. Thus, a person of ordinary skill in the art at the time of filing would have found it obvious to consult the teachings of Van Maris to improve the method made obvious by Lippmeier. Any suggestion to the contrary by Applicant is completely unpersuasive. The rejection over Lippmeier in view of Van Maris is maintained with modification to address the amendment of the claims and for clarity.
Claims 1 and 3-12 are rejected under 35 U.S.C. 103 as being unpatentable over Lippmeier in view of Van Maris and Demeke et al., 2013 (NPL cite 7, IDS, 8/1/2022; herein “Demeke”).
The discussion of Lippmeier and Van Maris regarding claims 1, 3-9 and 11 set forth in the rejection above is incorporated herein.
Lippmeier does not quantify the consumption of hemicellulosic xylose in culture medium comprising hemicellulosic xylose as the sole carbon source; however, a person of ordinary skill in the art at the time of filing would have found it obvious that the recombinant thraustochytrid microorganisms produced with the method made obvious by Lippmeier would consume at least 2 g/L/h hemicellulosic xylose in culture medium comprising hemicellulosic xylose as the sole carbon source in view of the disclosure of Demeke.
Demeke, like Lippmeier, teaches xylose-consuming microorganisms comprising two copies of a nucleic acid sequence encoding xylose isomerase and two copies of a nucleic acid sequence encoding a xylose kinase (Abst.; p. 3, “Results”, “Insertion of D-xylose utilization cassette into the Ethanol Red strain”) because Demeke teaches constructing yeast strains comprising integrating a D-xylose-utilization expression cassette into both alleles of the pyk2 locus, i.e., 2 copies of each of the genes in the expression cassette, wherein each copy of the D-xylose-utilization expression cassette comprises a nucleic acid sequence encoding xylose isomerase and a nucleic acid sequence encoding a xylose kinase (Abst.; p. 3, “Results”, “Insertion of D-xylose utilization cassette into the Ethanol Red strain”).
Demeke, like Lippmeier, teaches methods of producing microorganisms with increased xylose consumption using the xylose-consuming microorganisms comprising two copies of a nucleic acid sequence encoding xylose isomerase and two copies of a nucleic acid sequence encoding a xylose kinase wherein the increased xylose consumption is derived from a directed selection process comprising multiple rounds of growth in xylose-containing media. Demeke’s selection process comprises culturing the microorganisms in a first culture medium comprising xylose, harvesting a portion of the microorganisms from the first culture medium, culturing the harvested portion of microorganisms in a second culture medium comprising xylose, harvesting a portion of the microorganisms from the second culture medium, repeating the culturing and harvesting steps for a total of 11 cultures and isolating the harvested microorganisms, wherein the isolated microorganisms have increased xylose consumption rates compared to control xylose-consuming microorganisms, wherein the medium for the first through seventh culture contained 40 g/L xylose, the 8th culture comprised 50 g/L xylose, the 9th culture comprised 60 g/L xylose, the 10th culture comprised 100 g/L xylose and the 11th culture comprised 40 g/L xylose (pp. 5-6, “Directed Evolution”).
Demeke discloses that the microorganism produced by the directed evolution protocol, GS1.11-26, completely attenuated, i.e., consumed, 35 g/L xylose in about 17 h wherein the xylose was the sole carbon source (Abst.) which gives a consumption rate of 2.06 g/L/h (35 g/L xylose ÷ 17 h). Hence, a person of ordinary skill in the art at the time of filing would have found it obvious that the recombinant thraustochytrids produced by the method made obvious by Lippmeier would consume at least 2 g/L/h hemicellulosic xylose in culture medium comprising hemicellulosic xylose as the sole carbon source, especially if a graduated elevation of the level of xylose in the selection media is used as in Demeke, because Lippmeier demonstrates that directed selection of recombinant thraustochytrids in xylose-containing media increases the growth rate of the recombinant thraustochytrids using xylose as the sole carbon source and Demeke demonstrates that directed selection of recombinant microorganisms in xylose-containing media wherein a graduated elevation of the level of xylose in the selection media is used results in recombinant microorganisms that consume at least 2 g/L/h hemicellulosic xylose in culture medium comprising hemicellulosic xylose as the sole carbon source; therefore, claim 10 is prima facie obvious.
Fig. 5b of Demeke shows the consumption of xylose (open circle) by the microorganism produced by the directed evolution protocol, GS1.11-26, in a culture comprising glucose (36 g/L) and xylose (37 g/L) wherein the xylose concentration between 7.5 h and 10.5 h decreases from ~ 22 g/L xylose to ~ 5 g/L xylose giving a xylose consumption rate of (22 – 5 g/L) ÷ (10.5 h – 7.5 h) = 17 ÷ 3 = 5.67 g/L/h. Hence, a person of ordinary skill in the art at the time of filing would have found it obvious that the recombinant thraustochytrids produced by the method made obvious by Lippmeier in view of Van Maris and Demeke would consume at least 3 g/L/h hemicellulosic xylose in culture medium comprising hemicellulosic xylose and hemicellulosic glucose, especially if a graduated elevation of the level of xylose in the selection media is used as in Demeke, because Lippmeier demonstrates that directed selection of recombinant thraustochytrids in xylose-containing media increases the growth rate of the recombinant thraustochytrids on xylose and Demeke demonstrates that directed selection of recombinant microorganisms in xylose-containing media wherein a graduated elevation of the level of xylose in the selection media is used results in recombinant microorganisms that consume at least 3 g/L/h hemicellulosic xylose in culture medium comprising hemicellulosic xylose and hemicellulosic glucose; therefore, claim 12 is prima facie obvious.
Response to Arguments
Regarding the rejection of claims 1-12 under 35 U.S.C. § 103 over Lippmeier in view of Van Maris and Demeke, Applicant notes (p. 6) “As noted above, Van Maris is directed to producing a genetically modified S. cerevisiae yeast to increase bioethanol production and Lippmeier is directed to a method of producing engineered microorganisms to express polypeptides associated with xylose usage. Demeke describes producing a genetically modified Ethanol Red yeast to increase bioethanol production.” Applicant does explain the purpose of this “note”; however, it should be further noted that Demeke discloses methods of producing microorganisms with increased xylose consumption comprising providing xylose-consuming microorganisms comprising two copies of a nucleic acid sequence encoding xylose isomerase and two copies of a nucleic acid sequence encoding a xylose kinase wherein the increased xylose consumption is derived from a directed selection process comprising multiple rounds of growth in xylose-containing media. Demeke’s selection process comprises culturing the microorganisms in a first culture medium comprising xylose, harvesting a portion of the microorganisms from the first culture medium, culturing the harvested portion of microorganisms in a second culture medium comprising xylose, harvesting a portion of the microorganisms from the second culture medium, repeating the culturing and harvesting steps for a total of 11 cultures and isolating the harvested microorganisms, wherein the isolated microorganisms have increased xylose consumption rates compared to control xylose-consuming microorganisms, wherein the medium for the first through seventh culture contained 40 g/L xylose, the 8th culture comprised 50 g/L xylose, the 9th culture comprised 60 g/L xylose, the 10th culture comprised 100 g/L xylose and the 11th culture comprised 40 g/L xylose (pp. 5-6, “Directed Evolution”).
Hence, Demeke is clearly drawn to producing microorganisms with increased xylose consumption by a directed evolution method wherein the microorganisms express multiple heterologous xylose isomerase and xylulose kinase genes in a method comprising serially culturing the microorganisms in culture media with xylose wherein the xylose concentration increases with later rounds of the culturing and harvesting process. Thus, a person of ordinary skill in the art at the time of filing would have found it obvious to consult the teachings of Demeke to improve the method made obvious by Lippmeier. Any suggestion to the contrary by Applicant is completely unpersuasive. The rejection over Lippmeier in view of Van Maris and Demeke is maintained with modification to address the amendment of the claims and for clarity.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1 and 3-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-12 of copending Application No. 19/350363 (reference application; herein “’363”) in view of Lippmeier.
Claim 1 of ‘363 recites a method of making microorganisms with increased xylose consumption comprising
a. providing xylose-consuming microorganisms comprising two or more copies of a nucleic acid sequence encoding xylose isomerase and two or more copies of a nucleic acid sequence encoding a xylose kinase;
b. culturing the microorganisms in a first culture medium comprising xylose for at least 3 days;
c. harvesting a portion of the microorganisms from the first culture medium after culture step (b);
d. culturing the harvested portion of microorganisms in a second culture medium comprising xylose for at least 3 days;
e. harvesting a portion of the microorganisms from the second culture medium after culture step (d);
f. repeating culturing and harvesting steps (d) and (e) at least two times in a third culture medium and a fourth culture medium;
g. isolating the harvested microorganisms from step (f), wherein the isolated microorganisms have increased xylose consumption rates compared to control xylose-consuming microorganisms; and claim 2 of ‘363 recites the method of claim 1, wherein one or more of the culture media further comprises glucose.
‘363 does not recite that the xylose-consuming microorganisms comprises thraustochytrid microorganisms; however, a person of ordinary skill in the art at the time of filing would have found it obvious for the xylose-consuming microorganisms to comprise thraustochytrid microorganisms in view of the disclosure of Lippmeier.
Lippmeier is drawn to methods for producing recombinant thraustochytrids that grow on xylose, i.e., a method of making thraustochytrid microorganisms with increased xylose consumption (Abst.); hence, a person of ordinary skill in the art at the time of filing would have found it obvious for the xylose-consuming microorganisms in the method of ‘363 to comprise thraustochytrid microorganisms; therefore, instant claim 1 is prima facie obvious over claims 1-2 of ‘363 in view of Lippmeier.
Claims 3-12 of ‘363 recite identical limitations as instant claims 3-12, respectively; hence, instant claims 3-12 are prima facie obvious over claims 3-12 of ‘363.
This is a provisional nonstatutory double patenting rejection.
Claims 1, 3-4, 6-9 and 11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 18, 25, 27 and 32 of U.S. Patent No. 9951326 (herein “’326”) in view of Lippmeier in light of Diao.
Claim 18 of ‘326 recites a method of making a recombinant xylose-metabolizing Thraustochytrid microorganism comprising: providing one or more nucleic acid constructs comprising a nucleic acid sequence encoding a xylose isomerase, a nucleic acid sequence encoding a xylulose kinase and a nucleic acid sequence encoding a xylose transporter; transforming the Thraustochytrid microorganism with the one or more nucleic acid constructs; and isolating recombinant Thraustochytrid microorganisms comprising at least two or more copies of the nucleic acid sequences encoding the xylose isomerase; claim 25 of ‘326 recites the method of claim 18, wherein the isolated recombinant Thraustochytrid microorganism comprises at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21,22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40 copies of the exogenous nucleic acid sequence encoding xylose isomerase; claim 27 of ‘326 recites the method of claim 18, wherein the isolated recombinant Thraustochytrid microorganism comprises at least 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, or 40 copies of the nucleic acid sequence encoding the xylulose kinase; and claim 32 of ‘326 recites the method of claim 18, wherein the isolated recombinant Thraustochytrid microorganism has increased xylose transport activity as compared to a control non-recombinant microorganism, increased xylose isomerase activity as compared to a control non-recombinant microorganism, increased xylulose kinase activity as compared to a control non-recombinant microorganism, or a combination thereof.
Hence, claims 18, 25, 27 and 32 of ‘326 make obvious a method of making a recombinant xylose-metabolizing Thraustochytrid microorganism comprising providing xylose-consuming thraustochytrid microorganisms comprising two or more copies of a nucleic acid sequence encoding xylose isomerase and two or more copies of a nucleic acid sequence encoding a xylulose kinase wherein the isolated thraustochytrid microorganisms have increased xylose consumption rates compared to control xylose-consuming thraustochytrid microorganisms. Claims 18, 25, 27 and 32 of ‘326 do not specifically recite culturing the thraustochytrid microorganisms in a first culture medium comprising xylose for at least 3 days; harvesting a portion of the thraustochytrid microorganisms and culturing the harvested portion of thraustochytrid microorganisms in the next culture medium comprising xylose for at least 3 days; then repeating the rounds of culturing and harvesting for 4 to 25 rounds of selection wherein one or more of the culture media further comprises glucose; however, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method of making a recombinant xylose-metabolizing thraustochytrid microorganism made obvious by claims 18, 25, 27 and 32 of ‘326 wherein the method comprises culturing the thraustochytrid microorganisms in a first culture medium comprising xylose for at least 3 days; harvesting a portion of the thraustochytrid microorganisms and culturing the harvested portion of thraustochytrid microorganisms in the next culture medium comprising xylose for at least 3 days; then repeating the rounds of culturing and harvesting for 4 to 25 rounds of selection wherein one or more of the culture media further comprises glucose in view of the disclosure of Lippmeier.
Lippmeier is drawn to methods for producing recombinant thraustochytrids that grow on xylose, i.e., a method of making thraustochytrid microorganisms with increased xylose consumption (Abst.). Lippmeier teaches embodiments wherein the thraustochytrid comprises nucleic acid molecules encoding zero or more polypeptides associated with xylose import, two or more polypeptides associated with conversion of xylose to xylulose, and one or more polypeptides associated with phosphorylation of xylulose and embodiments wherein the thraustochytrid comprises nucleic acid molecules encoding zero or more polypeptides associated with xylose import, one or more polypeptides associated with conversion of xylose to xylulose, and two or more polypeptides associated with phosphorylation of xylulose [0053] wherein the polypeptides associated with conversion of xylose to xylulose can comprise a heterologous xylose isomerase and wherein the polypeptides associated with phosphorylation of xylulose can comprise a heterologous xylulose kinase [0052].
Lippmeier teaches that the recombinant thraustochytrids comprising heterologous xylose isomerase and heterologous xylulose kinase are further improved for growth on xylose, i.e., have increased xylose consumption, by serially culturing the recombinant thraustochytrids in xylose-containing liquid media for 19 rounds (Example 4, [0121-123]; Table 2). Lippmeier teaches [0121] that the liquid xylose-containing medium is xylose-SSFM which comprises 50 g/L xylose, i.e., 5 % xylose weight/volume [0114-115]. Lippmeier does not specify the length of culture for each round of selection in xylose-containing media; however, Lippmeier discloses that the recombinant thraustochytrids are grown in liquid media for 3 days for the expression of the heterologous proteins encoded by the nucleic acids [0120].
Lippmeier teaches that the purpose for producing recombinant thraustochytrids which can consume xylose is to provide recombinant thraustochytrids which can grow on alternative carbon sources such as hemicellulosic materials [0010-13], and discloses embodiments wherein the recombinant thraustochytrids are cultured in culture medium comprising hemicellulose-containing feedstock, such as corn stover [0061]. Diao is cited as evidence that corn stover hydrolysate comprises 44.9 g/L xylose and 63.2 g/L glucose, i.e., a corn stover hemicellulose-containing feedstock comprises both xylose and glucose. Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Lippmeier wherein the xylose source also comprises glucose because Lippmeier teaches that the carbon source in the culture medium can be hemicellulosic feedstock, such as corn stover, which comprise both xylose and glucose, and because Lippmeier teaches that the ultimate aim is to provide recombinant thraustochytrids which can grow on alternative carbon sources such as hemicellulosic materials
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method of producing thraustochytrid microorganisms with increased xylose consumption made obvious by claims 18, 25, 27 and 32 of ‘326 wherein xylose-consuming thraustochytrid microorganisms comprising two or more copies of a nucleic acid sequence encoding xylose isomerase and two or more copies of a nucleic acid sequence encoding a xylulose kinase are cultured in a first culture medium comprising xylose for 3 days; harvesting a portion of the thraustochytrid microorganisms from the first culture medium after culture; culturing the harvested portion of thraustochytrid microorganisms in a second culture medium comprising xylose for 3 days; harvesting a portion of the thraustochytrid microorganisms from the second culture medium after culture; repeating the culturing and harvesting at least two times in a third culture medium and a fourth culture medium; isolating the harvested thraustochytrid microorganisms wherein the isolated thraustochytrid microorganisms have increased xylose consumption rates compared to control xylose-consuming thraustochytrid microorganisms, wherein the thraustochytrid microorganisms are cultured for 3 days in one or more of the culturing steps, wherein the culturing and harvesting steps are repeated 19 times in 19 culture medias and wherein the media in the culturing steps comprises 50 g/L xylose, i.e., 5% xylose weight/volume, and glucose (from the hemicellulosic feedstock) because Lippmeier makes obvious culturing the thraustochytrid microorganisms in a first culture medium comprising xylose for 3 days; harvesting a portion of the thraustochytrid microorganisms from the first culture medium after culture; culturing the harvested portion of thraustochytrid microorganisms in a second culture medium comprising xylose for 3 days; harvesting a portion of the thraustochytrid microorganisms from the second culture medium after culture; repeating the culturing and harvesting at least two times in a third culture medium and a fourth culture medium; isolating the harvested thraustochytrid microorganisms wherein the isolated thraustochytrid microorganisms have increased xylose consumption rates compared to control xylose-consuming thraustochytrid microorganisms, wherein the thraustochytrid microorganisms are cultured for 3 days in one or more of the culturing steps, wherein the culturing and harvesting steps are repeated 19 times in 19 culture medias and wherein the media in the culturing steps comprises 50 g/L xylose, i.e., 5% xylose weight/volume, and glucose; therefore, claims 1, 3-4, 6-9 and 11 are prima facie obvious.
Conclusion
No claims are allowed.
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/TRENT R CLARKE/ Examiner, Art Unit 1651
/DAVID W BERKE-SCHLESSEL/ Primary Examiner, Art Unit 1651