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 .
Claim Status
Claims 1-4 and 14-24 are currently pending in this US patent application and were examined on their merits.
Information Disclosure Statement
The information disclosure statements filed in this application on 09/13/2022 and 01/16/2023 have been received and considered.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed application, Application No. 16/500786, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. The disclosure of ‘786 does not recite “Cytophaga sp. alpha-amylase” as recited in the amended instant claims of 09/13/2022. While the disclosure of ‘786 points to a specific Cytophaga alpha-amylase recited in the disclosure of WO 2013/184577 (see specification as filed, page 7, line 29), this disclosure is insufficiently broad to encompass any alpha-amylase from any species of microorganism in the genus Cytophaga, as recited in the instant claims. As such, the instant claims do not receive priority to 16/500786, and the effective filing date of the instant claims is filing date of the instant application, 10/04/2022.
Claim Objections
Claims 23-24 are objected to because of the following informalities:
Claims 23 and 24 both recite a group “consistint of” various limitations. These phrases should read “consisting of”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claim 21 is 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.
Regarding claim 21, the phrase "including" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). In addition, the recitation of a “low molecular weight” polyethylene glycol is a term of degree that renders the claim indefinite. While page 14 of the specification suggests that a “low molecular weight” PEG has a molecular weight of “about 900 or less,” no units are included in this recitation, and no explicit definition is provided. As such, one of ordinary skill in the art would be unable to determine the metes and bounds of claim 21, rendering it indefinite. Therefore, claim 21 is rejected under 35 U.S.C. 112(b).
In the interest of compact prosecution, the Examiner has interpreted claim 21 as reciting that the chemical enhancing the solubilization of the amylase is a polyol selected from the group consisting of a polyethylene glycol with a molecular weight of 900 Da or less and C2 to C8 alcohols having at least two OH groups.
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 1-4 and 14-24 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.
The disclosure as originally filed does not recite “Cytophaga sp. alpha-amylase” as recited in the amended instant claims of 09/13/2022. While the instant specification points to a specific Cytophaga alpha-amylase recited in the disclosure of WO 2013/184577 and particular variants of that specific enzyme (see specification as filed, page 7, line 29), this disclosure is insufficiently broad to encompass any alpha-amylase from any species of microorganism in the genus Cytophaga, as recited in the instant claims. As such, the instant claims incorporate new matter and are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement.
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 1-3, 14, 19-20, and 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over US patent 6316240 granted to Laustsen et al., issued 11/13/2001, in view of international patent application WO 2013/184577 filed by Cascao-Pereira et al., published 06/03/2013.
Laustsen teaches the recovery of a crystallized peptidase from a culture broth (see entire document, including column 1, lines 13-16, and column 2, lines 4-18). The culture broth may be a centrifuged fraction of a culture broth obtained after centrifugation containing cells, insoluble substrates, insoluble fermentation products, and insoluble protein of interest. The centrifuged fraction is then suspended or diluted in an aqueous solution, such as water, before the protein of interest is solubilized (column 4, lines 29-44; cf. claims 14 and 19; cf. part a) of claim 1; the Examiner notes that any fermentation broth with a protease concentration high enough to induce crystallization would have at least one molecule of soluble protease [i.e., “desired product in soluble form”], which would be present in the supernatant following centrifugation). A preferred enzyme of interest is an α-amylase (column 6, lines 45-59; cf. claim 1).
The solubilization is performed by adjusting the pH of the broth to a pH value of from pH 9.75 to pH 13 (column 4, lines 60-67, to column 5, line 1; cf. claim 19; cf. part b) of claim 1). Any agents known to mediate the solubilization of an insoluble protein, such as polyols, may also be added to the culture broth. Reference is made to WO 97/23604 for description of suitable components (column 4, lines 45-55; cf. claim 20). Stabilizers and protease inhibitors may also be added to the broth (column 6, lines 30-36; cf. claim 23). Following the solubilization, the broth containing the solubilized protein may be separated from the cells through multiple solid/liquid separatory steps, including centrifugation and filtration (column 6, lines 37-44; cf. claims 2 and 24; any removal of a substance from a mixture, such as through a filtration process, results in the concentration of the substances that remain in the mixture).
However, Laustsen does not teach that the α-amylase is from Cytophaga sp. as recited in instant claim 1.
Cascao-Pereira teaches α-amylase polypeptides that can be used for a variety of purposes, including starch liquefaction and saccharification, textile desizing, starch modification in the paper and pulp industry, brewing, baking, production of syrups for the food industry, production of feedstocks for fermentation processes, and in animal feed to increase digestability (see entire document, including pages 1-2, paragraph 005). An α-amylase from Cytophaga sp. is useful for these purposes (page 22, paragraph 0080; cf. claim 1).
While Laustsen does not teach that the protein crystals are crystals of α-amylase from Cytophaga sp., it would have been obvious to one of ordinary skill in the art to use the solubilization method of Laustsen on such crystals because Laustsen teaches that the method can be used on α-amylase crystals obtained from fermentation and because Cascao-Pereira teaches that the α-amylase from Cytophaga sp. is useful to produce through fermentation for industrial purposes. One of ordinary skill in the art would have a reasonable expectation that using the α-amylase solubilization method of Laustsen to solubilize crystals of an α-amylase from Cytophaga sp. as taught by Cascao-Pereira would successfully result in the production of the industrially useful enzyme.
While Laustsen teaches that stabilizers and protease inhibitors may be added to the fermentation broth, Laustsen does not specifically teach that these compositions be added to the broth prior to centrifuging the broth, as recited in instant claim 23. However, it would have been obvious to one of ordinary skill in the art to add stabilizers and protease inhibitors to the broth at the earliest point possible, including prior to the centrifugation to produce a spin down fraction of a culture broth as taught in column 4 of Laustsen, to prevent hydrolysis of the desired protease enzyme by other cellular proteases.
Laustsen and Cascao-Pereira do not teach the percentage of the liquid part of the fermentation broth that is removed prior to solubilization in the method rendered obvious by their teachings. However, the range of liquid removal recited in instant claim 3 would be within the realm of routine experimentation. Generally, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration 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). See MPEP § 2144.05 part II A. It would have been obvious to one of ordinary skill in the art at the time Applicants' invention was made to determine all operable and optimal concentrations of liquid supernatant allowed to remain after centrifugation because the concentration of all elements of the amylase-containing broth prior to solubilization is an art-recognized, result-effective variable known to affect the degree of solubilization of the amylase crystals and the amount of amylase purified from the fermentation process, which would have been optimized in the art to provide the desired amylase yield.
Therefore, claims 1-3, 14, 19-20, and 23-24 are rendered obvious by Laustsen in view of Cascao-Pereira and are rejected under 35 U.S.C. 103.
Claims 1-4, 14-20, and 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over US patent 6316240 granted to Laustsen et al., issued 11/13/2001, in view of international patent application WO 2013/184577 filed by Cascao-Pereira et al., published 06/03/2013, and European patent application EP 2125865 filed by Jakobsen et al., published 07/30/2014 (cited on the IDS filed 09/13/2022).
As discussed above, claims 1-3, 14, 19-20, and 23-24 are rendered obvious by Laustsen in view of Cascao-Pereira. However, these references do not teach the solubilization method discussed in instant claims 15-18.
Jakobsen teaches a method of solubilizing enzyme crystals in a fermentation broth (see entire document, including page 2, paragraph 0001). The yield of industrial enzymes is now so high that more than 60% of the enzymes in the fermentation broth may be present as crystals and/or precipitate (page 2, paragraph 0002; cf. claim 4). The fermentation broth contains enzyme crystals along with cells and other solids (page 3, paragraph 0026, to page 4, paragraph 0027; cf. part a) of claim 1 [“…desired product in precipitated form, cells and cell debris”]; the Examiner notes that any fermentation broth containing cells will also contain at least one molecule of a substance that can be interpreted as “cell debris”). The enzyme crystals are solubilized by diluting the fermentation broth with water to a preferred degree of 200-700% (w/w), adding a divalent salt that can be calcium chloride, adjusting the pH value of the fermentation broth to a pH value below 5.5, and removing the microorganism producing the enzyme of interest (page 3, paragraph 0026, to page 4, paragraph 0029; cf. claims 2 and 15-18; cf. part b) of claim 1). The solubilized enzyme may be further isolated by ultrafiltration, evaporation, crystallization, or spray-drying (page 5, paragraph 0047; cf. claim 24).
While the method of solubilizing the precipitated Cytophaga sp. alpha-amylase in the method rendered obvious by Laustsen and Cascao-Pereira is not the same as the method recited in instant claims 15-18, it would have been obvious to one of ordinary skill in the art to utilize the method recited in instant claims 15-18 because Jakobsen teaches that this series of steps is useful for the solubilization of precipitated enzymes that have been produced through industrial-scale fermentation processes. One of ordinary skill in the art would have a reasonable expectation that using the solubilization procedure of Jakobsen on the precipitated Cytophaga sp. alpha-amylase rendered obvious by Laustsen and Cascao-Pereira would successfully result in the solubilization of the amylase so it can be used in industrial applications.
Therefore, claims 1-4, 14-20, and 23-24 are rendered obvious by Laustsen in view of Cascao-Pereira and Jakobsen and are rejected under 35 U.S.C. 103.
Claims 1-3, 14, 19-21, and 23-24 are rejected under 35 U.S.C. 103 as being unpatentable over US patent 6316240 granted to Laustsen et al., issued 11/13/2001, in view of international patent application WO 2013/184577 filed by Cascao-Pereira et al., published 06/03/2013, and international patent application WO 97/23604 filed by Andre, published 07/03/1997.
As discussed above, claims 1-3, 14, 19-20, and 23-24 are rendered obvious by Laustsen in view of Cascao-Pereira. However, Laustsen and Cascao-Pereira do not teach the addition of the particular chemicals of claim 21 to the broth for solubilization.
Andre (the WO 97/23604 reference particularly cited by Laustsen as describing suitable agents for mediating the solubilization of an insoluble protein) teaches that diols and triols such as 1,2-ethanediol, 1,2-propanediol, 1,3-butanediol, and glycerol are preferred polyols to be added to fermentation broths (see entire document, including page 7, line 32, to page 8, line 2; cf. claims 20-21).
Laustsen and Cascao-Pereira do not teach the addition of diols and triols such as 1,2-ethanediol, 1,2-propanediol, 1,3-butanediol, and glycerol to the fermentation broth. However, Laustsen does teach that the polyols taught by Andre can be added to the fermentation broth for the mediation of the solubilization of the insoluble protein, and Andre teaches that diols and triols such as 1,2-ethanediol, 1,2-propanediol, 1,3-butanediol, and glycerol are preferred polyols to add to fermentation broths. One of ordinary skill in the art would have a reasonable expectation that adding the diols and triols such as 1,2-ethanediol, 1,2-propanediol, 1,3-butanediol, and glycerol as taught by Andre to the fermentation broth containing amylase crystals from fermentation as rendered obvious by the teachings of Laustsen and Cascao-Pereira would successfully result in the mediation of the solubilization of the amylase crystals.
Therefore, claims 1-3, 14, 19-21, and 23-24 are rendered obvious by Laustsen in view of Cascao-Pereira and Andre and are rejected under 35 U.S.C. 103.
Claims 1-3, 14, 19-20, and 22-24 are rejected under 35 U.S.C. 103 as being unpatentable over US patent 6316240 granted to Laustsen et al., issued 11/13/2001, in view of international patent application WO 2013/184577 filed by Cascao-Pereira et al., published 06/03/2013, and Kazan et al., J. Ind. Microbiol. Biotechnol. 32: 335-344 (2005; cited on the IDS filed 09/13/2022).
As discussed above, claims 1-3, 14, 19-20, and 23-24 are rendered obvious by Laustsen in view of Cascao-Pereira. However, these references do not teach adding the first phase from the first separation step partly or completely to the solubilized second phase as recited in instant claim 22.
Kazan teaches the isolation of enzymes from culture broths following fermentation (see entire document, including page 336, left column, paragraph 2). The dissolved proteins in the supernatant were precipitated. The precipitate was collected by centrifugation, dissolved in buffer, and applied to a DEAE-cellulose column. Fractions that eluted from the column were pooled based on specific enzymatic activity (page 336, left column, paragraph 5).
While Laustsen and Cascao-Pereira do not teach the isolation of the soluble alpha-amylase from the fermentation broth in addition to the isolation and solubilization of the amylase present in insoluble form in the fermentation broth, it would have been obvious to one of ordinary skill in the art to do so because Kazan teaches that soluble enzymes can be isolated from fermentation broths and because doing so would increase the overall yield of the amylase from the fermentation process. While Laustsen, Cascao-Pereira, and Kazan do not teach that the amylase present in soluble form from the fermentation broth is combined with the amylase that had been present in insoluble form in the fermentation broth and was subjected to the solubilization process rendered obvious by their teachings following the solubilization process as recited in instant claim 22, it would have been obvious to one of ordinary skill in the art to do so in order to obtain a single fraction of amylase produced by the fermentation. One of ordinary skill in the art would have a reasonable expectation that isolating the soluble amylase from the fermentation broth rendered obvious by Laustsen and Cascao-Pereira using the method taught by Kazan and then adding the isolated soluble amylase to the amylase fraction solubilized by the method rendered obvious by Laustsen and Cascao-Pereira would successfully result in the increased yield of amylase from the fermentation process.
Therefore, claims 1-3, 14, 19-20, and 22-24 are rendered obvious by Laustsen in view of Cascao-Pereira and Kazan and are rejected under 35 U.S.C. 103.
The Supreme Court has acknowledged:
When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable variation…103 likely bars its patentability…if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person’s skill. A court must ask whether the improvement is more than the predictable use of prior-art elements according to their established functions……the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results (see KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 U.S. 2007) (emphasis added).
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
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 1-4 and 14-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 and 14-24 of copending Application No. 18/356910 in view of international patent application WO 2013/184577 filed by Cascao-Pereira et al., published 06/03/2013. The claims of ‘910 recite a method that is identical to the instantly recited method except that the method of ‘910 produces different amylases than the Cytophaga sp. alpha-amylase recited in the instant claims. However, the production of the instantly recited enzyme through fermentation methods is discussed extensively in Cascao-Pereira, as discussed above. As such, the instant claims are ‘rendered obvious’ by the claims of ‘910 in view of Cascao-Pereira and are provisionally rejected on the ground of nonstatutory double patenting.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Erin M. Bowers, whose telephone number is (571)272-2897. The examiner can normally be reached on Monday-Friday, 7:30-5:00.
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/Erin M. Bowers/Primary Examiner, Art Unit 1653 06/05/2025