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 without traverse of Group I, claims 1-15, and the species Lipase, in the reply filed on 20 May 2026 is acknowledged. The requirement is deemed proper and therefore made Final.
Status of Application
Claims 1-15 are pending and subject to examination on the merits.
Priority
The instant application is a 371 of PCT/EP2022/0529587 filed 11 April 2022 which claims benefit of foreign priority document EP 21167712.5 filed 09 April 2021 is acknowledged. Said document has been received.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 09 October 2023 has been considered by the examiner. See initialed and signed PTO/SB/08.
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.
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 1-15 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 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).
The claims are drawn to methods of purifying any or all proteins produced by homologous or heterologous protein expression in any or all ciliate host cells, which are purified from harvested cell culture fluid (HCCF), wherein there is no chromatography step of the HCCF, and the method employs incubating the HCCF with a kosmotropic agent, efflorescing the protein by formation of crystals and optionally harvesting said efflorescing proteins. Thus, the methods are drawn to purification of an enormous genus of proteins, both homologous to the ciliate host cell, or any or all heterologous proteins expressed in said ciliate host cell. Furthermore, the method also employs a huge genus of ciliate host cells, ranging from Paramecium, Euplotes, Stentor, Kentrophoros, Tetrahymena, etc. However, the specification only describes the production of lipase of alpha-amylase in the ciliate Tetrahymena thermophila, using one of three precipitation/crystallization agents: ammonium sulfate, PEG and sodium dihydrogen phosphate. However, these very specific descriptions/species are not representative of the very large, variable and unpredictable genera of: ciliate host cells; proteins that are purified/crystallized; and agents used to perform the precipitation/crystallization and thus the purification step. It is notable not all proteins will readily crystallize and there will be a requirement for those skilled in the art to figure out which reagents and proteins are capable of crystallizing after being produced in a ciliate host cells. Thus, it is clear, Applicant’s are leaving it up to the rest of the industry to figure out Applicant’s claimed invention for them. See Novozymes A/S v. DuPont Nutrition Biosciences APS, 723 F.3d 1336 (Fed. Cir. 2013):
A patent, however, “is not a reward for the search, but compensation for its successful conclusion.” Ariad, 598 F.3d at 1353 (quoting University of Rochester, 358 F.3d at 930 n.10). For that reason, the written description requirement prohibits a patentee from “leaving it to the . . . industry to complete an unfinished invention.” Id.
Claim Rejections - 35 USC § 103
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.
Claim(s) 1-2, 4-6 and 8-15 are rejected under 35 U.S.C. 103 as being unpatentable over Hartmann et al. (WO 2016116600 – cited on IDS) in view of Nielsen et al. (US 5837513 – cited herein).
Hartmann et al. teach:
Regarding claims 1 and 2, methods of producing a lipase, such as SEQ ID NOs: 4-6 in the ciliate host cell of Tetrahymena thermophila – See Example 1, wherein SEQ ID NO:4 has 100% sequence identity to instant SEQ ID NO: 1 (See Supplemental Content, file 20260409_093327_us-18-554-513-1.rag, Result #1); SEQ ID NO: 5 has 100% sequence identity to instant SEQ ID NO: 2 (See Supplemental Content, file 20260409_093327_us-18-554-513-2.rag, Result #1); and SEQ ID NO: 6 has 95.7% sequence identity to instant SEQ ID NO: 3 (See Supplemental Content, file 20260409_093327_us-18-554-513-3.rag, Result #2).
Regarding claim 11, the promoter for expression of said lipase is selected from a heat-inducible promoter or metallothionein-promoter (MTT1) (See p. 18, 3rd paragraph), wherein MTT1 was specifically utilized (See Example 3).
It is specifically stated (See p. 11, 1st paragraph):
A ciliate based lipase production system provides an economical, simple and reliable method for the production of lipases, which have a drastically increased specific activity compared to the available competitors and thus a highly enhanced therapeutic potential.
Hartmann et al., however, do not teach specifically purifying the lipases produced in the ciliate Tetrahymena thermophila from HCCF.
Nielsen et al. teach: regarding claims 1 and 8-9, a method of rapidly and inexpensively purifying enzymes from an impure source such as harvested cell culture fluid (e.g. cell culture that has been filtered and centrifuged), by adding to the HCCF an effective amount of a crystallization agent which is a salt (i.e. a kosmotropic agent), wherein the enzymes are purified by crystallization within 12 hours, wherein no cross-linking takes place at any point in the method (See Claim 1, 16 and Examples). Regarding claim 4, the enzyme is present in a concentration of at least 5 g/L, most specifically, 5-66 g/L (See claims 17 and 18). Regarding claim 5, the crystallization takes place at temperature from about 15 to 30 oC or a pH or 4.5 to 7.5 (See claims 13 and 14, respectively). Regarding claim 6, the crystallization salt reagent is in a concentration of from 0.02 to 1.7M (i.e. 20 to 1700 mM). It is specifically taught the enzymes that is purified/crystallized is a lipase (See claims 1, 8 and 11 and Example 69). Regarding claim 15, the crystals are solubilized by the addition of water (See Figure 1). It is specifically stated (See Col. 1, lines 45-48):
Surprisingly it has been found that the method according to the invention which is simple and cheap, can be carried out with a yield of up to 95%, and that it can easily be adopted to industrial practice.
Therefore it would have been obvious to one of ordinary skill prior to the effective filing date of the claimed invention to purify the lipases of Hartmann et al., which are produced in a ciliate Tetrahymena thermophila host cell and to purify said lipases, which are indicated as being lipases with drastically increased specific activity compared to the available competitors and thus a highly enhanced therapeutic potential, and to purify using the methods of Nielsen et al. because they teach their methods specifically has been found is simple and cheap, can be carried out with a yield of up to 95%, and it can easily be adopted to industrial practice. This would be motivation in and of itself because it would be desirable to reduce costs of producing therapeutically effective enzymes as well as being simple and easy. One skilled in the art would have a reasonable expectation of success in combining the teachings of Hartmann et al. with Nielsen et al. because both teach producing and purifying lipase enzymes. As such, Nielsen et al. methods of purifying enzymes from different sources including lipases would be expected to readily be adaptable to the lipases of Hartmann et al.
Claim(s)1-6 and 8-15 are rejected under 35 U.S.C. 103 as being Hartmann et al. (WO 2016116600 – cited on IDS) in view of Hekmat et al. (Biotech. Lett 2015 – cited herein).
Hartmann et al. teach:
Regarding claims 1 and 2, methods of producing a lipase, such as SEQ ID NOs: 4-6 in the ciliate host cell of Tetrahymena thermophila – See Example 1, wherein SEQ ID NO:4 has 100% sequence identity to instant SEQ ID NO: 1 (See Supplemental Content, file 20260409_093327_us-18-554-513-1.rag, Result #1); SEQ ID NO: 5 has 100% sequence identity to instant SEQ ID NO: 2 (See Supplemental Content, file 20260409_093327_us-18-554-513-2.rag, Result #1); and SEQ ID NO: 6 has 95.7% sequence identity to instant SEQ ID NO: 3 (See Supplemental Content, file 20260409_093327_us-18-554-513-3.rag, Result #2).
Regarding claim 11, the promoter for expression of said lipase is selected from a heat-inducible promoter or metallothionein-promoter (MTT1) (See p. 18, 3rd paragraph), wherein MTT1 was specifically utilized (See Example 3).
It is specifically stated (See p. 11, 1st paragraph):
A ciliate based lipase production system provides an economical, simple and reliable method for the production of lipases, which have a drastically increased specific activity compared to the available competitors and thus a highly enhanced therapeutic potential.
Hartmann et al., however, do not teach specifically purifying the lipases produced in the ciliate Tetrahymena thermophila.
Hekmat et al. teach a method to purify, including lipase, by large-scale crystallization of said proteins for purification and formulations. It is stated that protein crystallization can replace one or more chromatography steps (See Abstract). It is specifically taught (See p. 1791, 1st col., Introduction):
Many proteins that are used in therapeutic applications or biomedical diagnostics need to be available in a highly purified form in large amounts. In order to achieve a high level of purity, several preparative packed-bed chromatography procedures are usually applied in a sequential manner. However, these procedures typically have low capacities and are time-consuming due to inherent mass transfer limitations (Przybycien et al. 2004). In addition, costly consumables are required for preparative chromatography. Therefore, non-chromatographic alternatives have been investigated.
They teach purification of lipase from a crude lipase formulation by crystallizing/purifying said lipase by adding NaCl and two different PEG molecules (mixture of PEG 1000 and PEG 8000 produced the best results. Said protein crystals were then resolubilized (See pp 1797-1798, Crystallization of Lipase). Protein purity after one crystallization step, one crystal wash and solubilization was 99% (See p. 1800, 1st col., Summary of purification performance). It finally stated (See p. 1801, 1st col., 1st paragraph):
The crystallization process is not mass transfer limited like chromatography. Sophisticated equipment is not required. Hence, a superb product quality and lower overall purification costs can be expected by applying preparative crystallization compared to chromatography, especially at large production scales. However, the economic advantages are not easily quantifiable at this time due to lack of data.
Therefore it would have been obvious to one of ordinary skill prior to the effective filing date of the claimed invention to purify the lipases of Hartmann et al., which are produced in a ciliate Tetrahymena thermophila host cell and to purify said lipases, which are indicated as being lipases with drastically increased specific activity compared to the available competitors and thus a highly enhanced therapeutic potential, and to purify using the methods of Hekmat et al. because they teach their methods specifically has been found is simple and effective, can be carried out with a purity of up to 99%, and it can remove many costly chromatography steps. This would be motivation in and of itself because it would be desirable produce high purity enzyme products for therapeutically effective enzymes as well as being simple and easy. One skilled in the art would have a reasonable expectation of success in combining the teachings of Hartmann et al. with Hekmat et al. because both teach producing and/or purifying lipase enzymes. As such, Hekmat et al. methods of purifying enzymes from different sources including lipases would be expected to readily be adaptable to the lipases of Hartmann et al.
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 17 August 2026
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