DETAILED ACTION
Notice of 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 .
Election/Restrictions
Applicant’s election of Group I, claims 1-8 and 10-15 in the reply filed on 20 July 2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The requirement is deemed proper and therefore made Final.
Status of Application
Claims 1-15 are pending; Claim 9 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected subject matter, there being no allowable generic or linking claim. Thus, claims 1-8 and 10-15 are subject to examination on the merits.
Priority
The instant application is a 371 of PCT/U S2022/014507 filed 31 January 2022.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 16 April 2026, 16 March 2026 and 31 July 2024 have been considered by the examiner. See initialed and signed PTO/SB/08’s.
Claim Objections
Claims 6 and 13 are objected to because of the following informalities: the word “tryptone” is misspelled in the claims as “typtone”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claims 8 and 15 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or join inventor regards as the invention. This is because the claims attempt to recite a process without setting forth any steps involved in the process. Specifically, the claims recite wherein the unicellular organisms “are used in food……”, however, it is unclear what the process steps are supposed to be which results in the unicellular organisms being used in food, feed, etc. It is noted, the recitation of a “use” without any active, positive steps delimiting how the use is practiced is deemed indefinite. See MPEP 2173.05(q).
Claim Rejections - 35 USC § 112(a)
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.
Written Description:
Claims 1-8 and 10-15 are rejected under 35 U.S.C. 112(a) 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 at the time the application was filed, had possession of the claimed invention.
The MPEP in section 2163(I) states that the purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made/filed, of the specific subject matter claimed:
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonable conclude 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. However, a showing of possession alone does not cure the lack of a written description. Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 969-70, 63 USPQ2d 1609, 1617 (Fed. Cir. 2002). For example, it is now well accepted that a satisfactory description may be found in originally-filed claims or any other portion of the originally-filed specification. See In re Koller, 613 F.2d 819, 204 USPQ 702 (CCPA 1980); In re Gardner, 475 F.2d 1389, 177 USPQ 396 (CCPA 1973); In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). However, that does not mean that all originally-filed claims have adequate written support. The specification must still be examined to assess whether an originally-filed claim has adequate support in the written disclosure and/or the drawings.
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An applicant shows that the inventor was in possession of the claimed invention by describing the claimed invention with all of its limitations using such descriptive means as words, structures, figures, diagrams, and formulas that fully set forth the claimed invention. Lockwood v. Amer. Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997)"
Further, for a broad generic claim, the specification must provide adequate written description to identify the genus of the claim. In Regents of the University of California v. Eli Lilly & Co. the court stated:
"A written description of an invention involving a chemical genus, like a description of a chemical species, 'requires a precise definition, such as by structure, formula, [or] chemical name,' of the claimed subject matter sufficient to distinguish it from other materials." Fiers, 984 F.2d at 1171, 25 USPQ2d 1601; In re Smythe, 480 F.2d 1376, 1383, 178 USPQ 279, 284985 (CCPA 1973) ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus ...") Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398 (Fed. Circ. 1997).
MPEP § 2163 further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is "not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence." Furthermore, the courts have also held that possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features. See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895.
The instant claims are drawn to a method for taurine production comprising: growing a unicellular organism in a shaker flask to produce at least 1 g/liter of taurine from the unicellular organism; and a method for taurine production comprising: growing a unicellular organism in a fermentor or bioreactor to produce at least 20 g/liter of taurine from the unicellular organism. Noting, exactly at what time point the 1 g/L or 20 g/L is achieved is unclear and exactly what volume of the shaker flask or fermentor/bioreactor utilized is also not clear. Thus, the claims are drawn to utilizing an enormous genus of unicellular organisms to produce taurine, wherein it is well known for most unicellular organisms, they do not naturally produce taurine, and they certainly do not produce 1 g/L in a shaker flask or 20 g/L in fermentor or bioreactor (See US 20240417763, cited herein, paragraphs 0002-0023). For unicellular microorganisms to produce these levels of taurine, each unicellular microorganism must be engineered to possess a synthetic taurine biosynthetic pathway. While the prior art demonstrates various biosynthetic pathways have been created, for example, in E. coli and C. glutamicum (See KR-20100130564, WO 2019094051, both cited in IDS’s; and Joo et al., J. Ag. And Food Chem., 2018 – cited herein), how to achieve the 1 g/L in a shaker flask or 20 g/L in fermentor or bioreactor levels has not been disclosed. As such, this makes the genus of microorganisms being utilized in the claimed methods as unpredictable. In addition, the specification only discloses five strains of E. coli manipulated microorganism which may or may not be able to achieve these levels; wherein these five strains are Strain 1: CDO-SAD cysQ cysH/cysIJ and pgk/serAΔ197/serC/serB/cysEM201R cysK introduced into an E. coli K12 ΔtauABCD/ΔssuEADCB/trcPUWA/trcDNC strain. Strain 2: CDO SAD/cysQ/cysH/cysIJ/sbp and gk/serAΔ197/serC/serB/cysEM201R/cysK introduced into a ΔtauABCD/ΔssuEADCB/ΔsdaA/ΔglyA/trcDNC/trcUWA strain. Strain 3: pgk/serAΔ197/serC/serB and CS/PLP-DC/IlvAL447F introduced into a ΔtauABCD/ΔssuEADCB/ΔsdaA/ΔglyAltrcDNC/ΔridA/ΔtdcF/ΔrutC strain.
Strain 4: pgk/serAΔ197/serC and TS/partCS/PLP-DC introduced into a ΔtauABCD/ΔssuEADCB/ΔsdaA/ΔglyA/trcDNC strain. Strain 5: CDO/SAD/gadC and pgk/serAΔ197/serC/serB introduced into a ΔssuE/ΔmcbR/ΔilvA/glyA strain.
However, these five strains are not representative of the entire enormous, diverse and unpredictable genus of unicellular microoragnisms utilized to make the claimed levels of taurine.
In addition, there are many other considerations that are required for the claimed method for the engineered unicellular microorganism to make said levels of taurine such as time, temperature, volume of shaker/fermentor/bioreactor/ and culture/fermentation medium.
Scope of Enablement:
Claims 1-8 and 10-15 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of producing at least 1 g/L of taurine in a shaker flask or at least 20 g/L of taurine in a fementor/bioreactor by utilizing the following genetically engineered E. coli strain selected from the group consisting of:
Strain 1: CDO-SAD cysQ cysH/cysIJ and pgk/serAΔ197/serC/serB/cysEM201R cysK introduced into an E. coli K12 ΔtauABCD/ΔssuEADCB/trcPUWA/trcDNC strain;
Strain 2: CDO SAD/cysQ/cysH/cysIJ/sbp and gk/serAΔ197/serC/serB/cysEM201R/cysK introduced into a ΔtauABCD/ΔssuEADCB/ΔsdaA/ΔglyA/trcDNC/trcUWA strain;
Strain 3: pgk/serAΔ197/serC/serB and CS/PLP-DC/IlvAL447F introduced into a ΔtauABCD/ΔssuEADCB/ΔsdaA/ΔglyAltrcDNC/ΔridA/ΔtdcF/ΔrutC strain;
Strain 4: pgk/serAΔ197/serC and TS/partCS/PLP-DC introduced into a ΔtauABCD/ΔssuEADCB/ΔsdaA/ΔglyA/trcDNC strain; and
Strain 5: CDO/SAD/gadC and pgk/serAΔ197/serC/serB introduced into a ΔssuE/ΔmcbR/ΔilvA/glyA strain.
Wherein the method comprises growing said E. coli strain in a shaker flask or fermentor/bioreactor at 30oC for at least 20 hours and in a growth medium comprising either: at least 5 g/L ammonium sulfate, at least 6 g/L dibasic potassium, at least 3 g/L monobasic sodium phosphate, at least 0.5 g/L magnesium sulfate, at least 6 g/L glucose, at least 0.1 g/L tryptone, at least 0.05 g/L yeast extract, and at least 2.4 mg/L PLP, with or without antibiotic(s); OR at least 2 g/L yeast extract, at least 40 g/L glucose, at least 10 g/L calcium carbonate, at least 15 g/L ammonium sulfate, at least 1 g/L dibasic potassium phosphate, at least 1 g/L monobasic potassium phosphate, at least 2 g/L sodium chloride, at least 80 mg/L calcium chloride, at least 3 mg/L ferric chloride, at least 0.9 mg/L zinc sulfate heptahydrate, at least 0.2 mg/L cupric sulfate, at least 0.4 mg/L manganese sulfate, at least 0.1 mg/L sodium molybdate, at least 0.3 mg/L sodium borate, at least 1 g/L magnesium sulfate, at least 0.2 mg/L thiamine hydrochloride, at least 0.2 mg/L biotin, and at least 2.4 mg/L PLP, with or without antibiotic(s); to produce at least 1 g/L of taurine in a shaker flask or 20 g/L in fermentor/bioreactor, does not reasonably provide enablement for methods of growing any unicellular microorganism in any conditions, for any length of time and temperature in a shaker flask or bioreactor/fermentor in order to produce at least 1 g/L or 20 g/L, respectively, of taurine. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The court in Wands states: "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue,' not 'experimentation.' " (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.
The SCOTUS in Amgen warned that “the more one claims, the more one must enable” Amgen Inc. v. Sanofi, 143 S. Ct. 1243, 1254, 1257 (2023). The Court also made clear that providing “research assignments” to the public to identify claimed species of a genus in trial and error fashion was improper.
Here, the quantity of experimentation necessary to genetically engineer a unicellular microorganism to produce the quantities of taurine claimed would be huge. This is because unicellular microorganisms do not naturally possess taurine biosynthetic pathways and thus, for each different species of microorgranism, a heterologous taurine biosynthetic pathway must be created. While the prior art demonstrates this has been achieved before in E. coli and C. glutamicum (See KR-20100130564, WO 2019094051, both cited in IDS’s; and Joo et al., J. Ag. And Food Chem., 2018 – cited herein and US 20240417763, cited herein, paragraphs 0002-0023), what has not been disclosed in the prior art is the claimed levels of taurine of at least 1 g/L in a shaker flask and at least 20 g/L in fermentor/bioreactor. In addition, there are many other considerations for the method to be achieved that one skilled in the art must figure out such as the time of growth, the temperature, the culture/fermentation medium all which have a direct impact on the levels of taurine a microorganism can produce (but only after an exogenous taurine biosynthetic pathway has been introduced). The working examples in the specification are limited to five E. coli strains, and to specific growth conditions and culture media conditions, as noted above, which produce the claimed yields of taurine. While the level of skill in the art is high, graduate level and above, said skilled artisan would necessarily have to practice in a trial and error fashion to try to achieve the claimed levels of taurine produced by a unicellular microorganism. The trial and error would be a result of having to figure out which microorganism to start with, out of the millions possible, and then having to genetically engineer each one just to see if they are able to achieve the claimed taurine production levels because the predictability of such genetic engineering is very low when it comes to the resultant taurine/product production levels. As noted above, the Supreme Court in Amgen Inc. v. Sanofi, 143 S. Ct. 1243, 1254, 1257 (2023) made it clear that providing this kind of “research assignments” to the public/skilled artisan to identify claimed species of a genus in trial and error fashion was improper.
As such, the breadth of claims exceed that which is enabled because the amount of direction and guidance in the specification and working examples coupled with what is known in the art suggests that the instant method claims will be highly unpredictable thus leading one skilled in the art to a huge amount of undue experimentation, despite the high level of skill of said artisan.
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 1-8 and 10-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 and 30-33 of copending Application No. 19317818 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because are obvious variations of one another.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The instant claims in their broadest are drawn to methods of growing any unicellular microorganism in any conditions, for any length of time and temperature in a shaker flask or bioreactor/fermentor in order to produce at least 1 g/L or 20 g/L, respectively, of taurine. With dependent claims reciting wherein the unicellular unicellular organism is E. coli and the growing step is conducted in a media that contains at least 5 g/L ammonium sulfate, at least 6 g/L dibasic potassium phosphate, at least 3 g/L monobasic sodium phosphate, at least 0.5 g/L magnesium sulfate, at least 6 g/L glucose, at least 0.1 g/L tryptone, and at least 0.05 g/L yeast extract (claims 6 and 13). And wherein the unicellular organism expresses one or more exogenous taurine biosynthetic pathways and contains one or more of the following:
a deletion of at least one operon for taurine or sulfonate uptake and degradation;
an exogenous taurine exporter;
increased expression of genes in sulfate or thiosulfate transport, or sulfur reduction or sulfur assimilation;
increased expression of a gene in the serine biosynthetic pathway;
increased expression of a gene in the cysteine biosynthetic pathway;
increased expression of a gene in the 2-aminoacrylate biosynthetic pathway;
a deletion of at least one gene in the degradation of taurine, serine, cysteate or 2-aminoacrylate; or
modified expression of a gene for a transcriptional regulator or activator for taurine, sulfur, or cysteine metabolism (claims 3 and 10).
The claims to the ‘818 application in their broadest are drawn to genetically engineered microorganisms comprising at least a mutated SerB polypeptide, which are used to make at least 0.25 g/L of taurine in a shake flask, or at least 15 g/L of taurine in a fermentor/bioreactor; and wherein the modified microorganisms comprise he recombinant microbe or unicellular organism comprises: (i) one or more exogenous polynucleotides comprising a sequence encoding a threonine synthase (TS) polypeptide or cysteate synthase (CS) polypeptide; and (ii) one or more exogenous polynucleotides comprising a sequence encoding a sulfinoalanine decarboxylase (SAD) polypeptide, a cysteic acid decarboxylase (CAD) polypeptide, a glutamate decarboxylase (GAD) polypeptide, or a polypeptide corresponding to a decarboxylase portion of the cysteine synthetase/PLP decarboxylase (partCS/PLP-DC), or a combination thereof; or [[c]]1) the recombinant microbe or unicellular organism comprises (i) a modified O- phosphoserine pathway comprising increased expression of pgk, serAAJ97, serC, or a combination thereof; and (ii) [[and ]]a modified sulfur-based pathway comprising (a) increased expression of cysPUWA, cysDNC, cysQ or cysH , and a gene knock-out of tauD, ssuD, and ssuE to inhibit taurine degradation, or (b) a gene knock-out of tauABCD, ssuEADCB, ssuD1CBA, sueABCD2, or a combination thereof to inhibit taurine degradation and reuptake of taurine into the cell. These unicellular microorganisms will inherently be capable of producing at least 1 g/L in a shaker flask or at least 20 g/L in a fermentor/bioreactor, given they are the same constructs utilized in the instant examples.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUZANNE M NOAKES whose telephone number is (571)272-2924. The examiner can normally be reached M-F (7-4).
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/SUZANNE M NOAKES/Primary Examiner, Art Unit 1656 25 September 2026
