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 .
DETAILED ACTION
This application has provisional application 63/459262, filed April 14, 2023.
Applicant's Preliminary amendment filed June 9, 2024 is acknowledged. Claim 17 is
amended. Currently claims 1-20 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on June 22, 2026 is acknowledged. Claims 17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on June 22, 2026. Currently claims 1-16 are under examination.
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 1-16 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.
Claims 1-16 recite a method for producing a bioproduct comprising culturing at least one target microorganism in a target growth medium comprising cells of a strictly anaerobic bacterium, said cells comprising protein at a crude protein concentration of at least 60wt% of a total dry weight of said cells, wherein at least 50% of a total number of said cells are dead cells. Claim 7 recites the target microorganism is capable of at least partially hydrolyzing said protein of said cells. 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.
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 specification does not disclose any working examples, but does disclose that strictly anaerobic bacterium refers to a bacterium which are unable to grow in the presence of normal atmospheric concentrations of oxygen, and non-limiting examples of strictly anaerobic bacteria include bacteria of the genera Actinomyces, Bacteroides, Clostridium, Fusobacterium, Peptostreptococcus, Porphyromonas, Prevotella, Propionibacterium, and Veillonella. However, the specification does not describe strictly anaerobic bacterial cells as having a ‘crude protein concentration of at least 60wt%’, nor describes a population wherein at least 50% of the cells are dead. The specification discloses the target organism is the major microorganism intended to be produced by the culturing process and can be a bacterium, a yeast, a mold, a fungus, or archaea, and according to some embodiments, is a lactic acid bacterium of the genus lactobacillus, and are the only species whose complete structure is disclosed. The specification also discloses the target microorganism is capable of hydrolyzing at least 5% of the protein of the cells.
While the genus encompasses a large number of variants that are categorically “crude protein of at least 60wt% of total dry weight of strictly anaerobic bacterium and wherein 50% are dead cells” and a “target microorganism capable of at least partially hydrolyzing said protein of said cells” in kind and the genus encompasses a large number of variants that have a different structure, the specification does not describe the complete structure of a representative number of species of the large genus of variants or functional equivalents thereof, especially considering the specification does not provide working examples, experimental data, methods of preparation, or other disclosure demonstrating possession of bacterial cells having the claimed combination of characteristics.
Next, then, it is determined whether a representative number of species have been sufficiently described by other relevant identifying characteristics, specific features and functional attributes that would distinguish different members of the claimed genus. In the instant case, there are no other identifying characteristics of a ‘crude protein of at least 60wt% of total dry weight of strictly anaerobic bacterium and wherein 50% are dead cells’ and a ‘target microorganism capable of at least partially hydrolyzing said protein of said cells’ that distinguish different members of the claimed genus, and such broad limitations cannot be identifying characteristics for the claimed diverse genus of variants since by Applicant’s definition of variant or functional equivalent thereof all members of the claimed genus will have that characteristic
The inventions of claims 2-6 and 8-16 require the use of the inventions of claims 1 and 7, and therefore are likewise rejected under 35 U.S.C. 112, first paragraph, as failing to comply with the written description requirement.
Applicant’s attention is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112(a) or Pre-AIA 35 U.S.C. 112, first paragraph, "Written Description" Requirement (MPEP2163).
In conclusion, Applicant’s disclosure of the species of ‘crude protein of at least 60wt% of total dry weight of strictly anaerobic bacterium and wherein 50% are dead cells’ and a ‘target microorganism capable of at least partially hydrolyzing said protein of said cells’ of the claimed broad genus is not deemed sufficient to reasonably convey to one skilled in the art that Applicant was in possession of the claimed broad genus at the time the application was filed. Thus, it is concluded that the written description requirement is not satisfied for the claimed genus.
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-16 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites “at least one target microorganism in a target growth medium comprising cells of a strictly anaerobic bacterium”. It is unclear whether the “target microorganism” or the “target growth medium” is required as comprising cells of a strictly anaerobic bacterium. The specification discloses, in some embodiments, the target microorganism is from the genus lactobacillus, and the strictly anaerobic bacterium is Clostridium tyrobutyricum, however there is no clear definition of the “target microorganism” and one of ordinary skill in the art would not be apprised of the metes and bounds of the claim. The same issue arises in claim 10 reciting “at least one target microorganism comprises at least one bacterium”, however if claim 1 is interpreted as the target microorganism comprising cells of a strictly anaerobic bacterium, the claim limitation would not be further limited in claim 10, and thus ambiguity would be present as to what exactly the target microorganism comprises. Another interpretation of the claim could be that the target microorganism is co-cultured with the strictly anaerobic bacterium, which is comprised in a target growth medium from an earlier inoculation or initial growth before the target microorganism is added.
Claim 1 also recites “a crude protein concentration of at least 60wt% of a total dry weight of said cells, wherein at least 50% of a total number of said cells are dead cells”. It is unclear what constitutes ‘crude protein concentration’ as this could be interpreted as the protein concentration of dead cells to live cells, or some other undefined bioproduct produced by the strictly anaerobic bacterium.
The term “predetermined” in claim 2 is a subjective term which renders the claim indefinite. The term “predetermined cell concentration” is not defined by the claim, the specification does not provide some objective standard in order to allow the public to determine the scope of the claim. The specification discloses that, according to some embodiments, the predetermined cell concentration is 1 x 106 colony forming unit, however there is no disclosed reason for bringing the cell concentration to a threshold for purposes in the method.
Claim 5 recites: The method of claim 2, wherein said cells are cultured in said cell growth medium comprising an oxygen concentration of less than 1%; and oxygen is added to said cell growth medium to provide an oxygen concentration of between 1 and 21% prior to or simultaneously with combining with said target microorganism. It is unclear how the limitations of this claim are incorporated in the steps recited in claim 2, particularly when the oxygen is added to the cell growth medium before the predetermined cell concentration is reached or after.
Claim 7 recites: said target microorganism is capable of at least partially hydrolyzing said protein of said cells. The term “at least partially” is a relative term which is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear what would fall under the scope of “at least partially hydrolyzing”, such as a percentage of hydrolysis, under specific undisclosed parameters, if hydrolyzing one peptide bond would count.
Claims 3-4, 6, 8-9, and 11-16 are likewise rejected as being dependent on an indefinite claim.
Claim Interpretation
Claim 6 recites “wherein said target microorganism is aerobic”, however the Specification does not define the specific parameters that qualify as aerobic (such as oxygen tolerance), thus for purposes of applying prior art, the Examiner interprets ‘aerobic’ as a microorganism that is tolerant to and able to grow in various oxygen levels (i.e. aerotolerant).
Claim Rejections - 35 USC § 103
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 1-6, 8, and 10-16 are rejected under 35 U.S.C. 103 as being unpatentable over Shahab et al. (Science, 2020, 369, 1073, pgs. 1-11, hereinafter “Shahab”).
Regarding claims 1, 4, 6, 8, and 10-16, Shahab teaches a heterogenous microbial consortium producing short chain fatty acids from lignocellulose, wherein the consortia comprises an aerobic fungus Trichoderma reesei, an oxygen-tolerant (i.e. aerobic) bacterium Lactobacillus pentosus, and a strictly anaerobic bacterium Clostridium tyrobutyricum to produce a target product butyric acid (title, pg. 3, col. 1). Shahab teaches a membrane bioreactor was inoculated with 5%(v/v) T. reesei, and after 48 hours, the lactic acid bacteria were inoculated to an optical density (OD600) of 0.5 by centrifuging the cells at 3000 rpm for 10min and suspending them in fresh Mandels medium, and after another 48 hours after inoculation of the LAB, the C. tyrobutyricum was inoculated to 5% (v/v) from a 2-day-old pre-culture (pg. 7, col. 2, para 1). Shahab teaches the butyric acid was approximately 4 g/L after 150 hours of culturing (pg. 3, Fig. 2A). Although Shahab does not disclose the amount of total dry weight of C. tyrobutyricum compared with the crude protein concentration, generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). Furthermore, the limitation of “wherein at least 50% of a total number of said cells are dead cells”, is implicit when cells are processed to generate a lysate and recovering the target product, as disclosed in the analytical methods taught by Shahab (pg. 7, col. 3, para 3).
Regarding claims 2-3, Shahab teaches the L. pentosus is inoculated to MRS medium for precultures of Lactobacillus in 500-ml Erlenmeyer flasks and incubated for 48 hours at 150 rpm at 33°C, and C. tyrobutyricum precultures were cultivated in a reinforced clostridial medium (RCM) (pg. 6, col. 3, para 4-5), then the LAB were suspended in fresh Mandels medium, and C. tyrobutyricum was incoluated to 5% (v/v) (pg. 7, col. 2, para 1), which meets the limitations of the (strictly anaerobic) cells precultured in a different medium then combined with the LAB (target microorganism) in claims 2-3.
Regarding claim 5, Shahab teaches the membrane aerated reactor in combination with the facultative anaerobic LAB, an oxygen gradient is generated in the reactor that allows the redox potential requirements of all strains to be fulfilled, (pg. 1, col. 3, para 3). Shahab teaches the metabolic activity of T. reesei reduced the dissolved oxygen content below the detection limit within 8 to 12 hours after fungal inoculation and lowered the redox potential to values between +20 and –20mV, and upon inoculation of L. pentosus, the redox potential dropped to less than –300 mV by reduction of oxygen to either hydrogen peroxide or water for the regeneration of nicotinamide adenine dinucleotide (NAD+) by NADH oxidases, thereby creating suitable growth conditions for C. tyrobutyricum (pg. 3, col. 2, para 1). Thus, the preculturing of C. tyrobutyricum requires oxygen content below the detection limit for its’ growth, thus would inherently meet the limitation of less than 1% oxygen, and when combined into the consortia, would inherently increase the oxygen concentration in the medium due to the oxygen requirements of the other strains in the consortia.
In view of the foregoing, all the claimed limitations are found in one reference and are taught to be optional variations to a ‘base’ method they exemplify. As such, the method taught by Shahab is within the scope of the instant claims, and thus Shahab’s method renders the invention prima facie obvious. The rationale to support this conclusion of obviousness is that Shahab provides teaching, suggestion and motivation to substitute different variables disclosed within the reference. Furthermore, there is no evidence on the record that indicates that the claimed method exhibits any unexpected results compared to the prior art method.
Claims 1-3 and 5-13 are rejected under 35 U.S.C. 103 as being unpatentable over Reed et al. (WO 2021/151025 A1, cited in IDS filed 6/22/2026, hereinafter “Reed”).
Regarding claims 1-3 and 6-13, Reed teaches a protein hydrolysate composition derived from microorganisms, and methods of preparing the protein hydrolysate composition and finds use in supplementing culture media for growing other types of cells such as probiotics and lactic acid bacteria, providing sustainable, humane processes for culturing cells for pharmaceutical and nutraceutical application as well as for human consumption as a food ingredient or product (abstract). Reed teaches protein hydrolysate derived from chemoautotrophic microorganisms including an obligate anaerobic Methanogenium sp. (i.e. strictly anaerobic) [179]. Reed teaches extensive genetic lesions of the arginine and pyrimidine biosynthetic pathways in Lactobacillus plantarum, L. paraplantarum, L. pentosus, and L. casei occur due to their long adaptation to milk, which is a fairly nutritious growth medium, thus amino acid requirements and transport systems are known to be growth-limiting factors in Lactococci, therefore the protein hydrolysate from other microorganism sources can be provided to culture LAB that have lost certain proteolytic activity and/or acquired amino acid auxotrophy due to evolution on milk substrates [252], thus the LAB hydrolyzes the protein derived from the chemoautotrophic microorganism for increase in biomass and production of a bioproduct (such as dairy products), meeting the limitations in claims 1 and 7.
Reed teaches production of the protein hydrolysate of Cupriavidus necator (a facultative anaerobe) wherein the total protein content of the biomass is given in relation to the defatted biomass, which is 84.96% of amino acid content, wherein the culture is cultivated chemoautotrophically in a mineral salts growth medium with CO2 as carbon source and H2 as electron donor, and then the biomass was isolated from the growth medium by centrifugation and dried by lyophilization, then defatted for application (Example 1, Table 1 [313-318]), thus meeting the limitation of at least 60% crude protein to total dry weight and 50% total number cells are dead in claim 1.
Reed teaches the protein hydrolysate from C. necator may be used in the formulation of a growth medium for another culture such as a LAB strain, and the formulation may include a source of carbohydrates (e.g. lactose) [221], thus meeting claims 8-9. Reed teaches in Example 6, the C. necator protein hydrolysate is applied for promoting growth of lactic acid bacteria (i.e. Lactobacillus delbrueckii, an aero-tolerant facultative anaerobe, meeting limitations in claims 6 and 10-13), wherein the protein hydrolysate is mixed with Elkier broth for LAB culture [338-343], thus meeting the limitations of claims 1-2, and the composition of cell growth medium is different from target medium in claim 3.
In view of the foregoing, all the claimed limitations are found in one reference and are taught to be optional variations to a ‘base’ method they exemplify. As such, the methods taught by Reed are within the scope of the instant claims, and thus Reed’s methods render the invention prima facie obvious. The rationale to support this conclusion of obviousness is that Reed provides a teaching, suggestion, and motivation to substitute different variables disclosed within the reference. Furthermore, there is no evidence on the record that indicates that the claimed method exhibits any unexpected results compared to the prior art method.
Regarding claim 5, Reed does not explicitly teach the oxygen concentration of the cell growth medium (the chemoautotrophic microorganism), however Reed teaches during the protein production, dissolved oxygen (DO) may be optimized by maintaining the broth in aerobic, microaerobic, anoxic, anaerobic, or facultative conditions, depending upon the requirements of the microorganisms [117], thus it would have been routine optimization and a well-understood practice in the art to adjust the desired oxygen levels for optimal growth and protein production of the anaerobic bacterium/chemoautotrophic microorganism, therefore prima facie obvious.
Conclusion
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/JESSICA EDWARDS/
Examiner, Art Unit 1657
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