The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-58 are canceled. Claims 59-78 are pending and under consideration.
Priority: This application is a 371 of PCT/IB2021/061943, filed December 17, 2021, which claims benefit of provisional applications 63/199368, filed December 21, 2020, and 63/263924, filed November 11, 2021.
Specification/Drawings
The use of the terms TRITON™ X-100, TRITON™ X-100, TWEEN® 20, TWEEN® 40 (see application publication at least Figs. 7A, 7B, 7C, paragraphs 0013, 0018, 0019, 0020, 0021, 0029, 0030, 0032, 0033, etc.), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Due to the large number of paragraphs in the specification reciting the noted terms without a proper symbol, not all the paragraphs reciting terms without a proper symbol have been listed above. Applicants should review the entirety of the specification and accompany any terms with the generic terminology and the proper symbol. See also MPEP 608.01(v).
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claim 78 is rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter. The instant claim is a product claim reciting a biological product produced by a host cell that is not markedly different from naturally occurring biological products.
Claim 78 is directed to a biological product produced by a host cell. The claim is directed to a statutory category, i.e. a composition of matter (Step 1: YES). The biological product can be any natural biomolecule (i.e. protein) produced by a host cell. Because the claim is a nature-based product, i.e. including any natural biomolecule, the nature-based product is analyzed to determine whether it has markedly different characteristics from any naturally occurring counterpart(s) in their nature state. Biological products are found in nature and in any host cell. The claim thus encompasses biological products that are identical (no difference in characteristics) to naturally occurring biological products. Since there is no difference between the claimed and naturally occurring biological products, the claimed biological product does not have markedly different characteristics, and thus, is a “product of nature” exception. Accordingly, the claim is directed to an exception (Step 2A: YES). The claim as whole does not recite anything significantly different than the natural product, i.e. the claim does not include elements or features that demonstrate that the biological product, which in this instance, can include a naturally occurring protein, is markedly different from what exists in nature. The claim does not include any additional features that could add significantly more to the exception (Step 2B: NO), and thus, the claim does not qualify as eligible subject matter. See Funk Brothers Seed Co., V. Kalo Inoculant Co., 333 U.S. 127, (1948) and Association for Molecular Pathology v. Myriad Genetics, Inc. 569 U.S., 133 S. Ct. 2107, 2116, 106 USPQ 2d. 1972 (2013).
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 59-60, 64, 75-76, 78 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by De Vocht et al. (WO 2011045381). De Vocht et al. teach methods for purifying adenovirus particles from host cells, using host cell DNA fragmentation and/or precipitation followed by clarification (at least abstract, p. 2-3). De Vocht et al. teach preferably adding domiphen bromide (DB) for select removal of contaminating host cell DNA from a high density cell suspension containing virus particles (at least p. 8 lines 20 to p. 9 lines 15). De Vocht et al. teach a method for selective host cell DNA precipitation in high cell density, comprising lysing host cells by adding nonionic detergents Triton X-100 and Tween-80, adding domiphen bromide to the lysed harvest to concentrations of 0.72 and 1.52 mM in 40 mM NaCl, clarifying the precipitated lysate with filters, where the filters remove large cell debris, impurities and precipitated DNA, from the virus-containing suspension (at least p. 21 example 3, see also example 4). Therefore, De Vocht et al. can be deemed to anticipate at least instant claim 59.
Regarding instant claim 60, De Vocht et al. teach high cell density suspensions, including 16.7 x 106 cells/mL (at least p. 21-22, example 3, see also example 4).
Regarding instant claim 64, since De Vocht et al. teach addition of 40 mM NaCl (examples 3-4), De Vocht et al. can be deemed to teach a sufficient concentration that inhibits DNA precipitation.
Regarding instant claim 75, De Vocht et al. do not teach adding an exogenous endonuclease (examples 3-4).
Regarding instant claim 76, De Vocht et al. teach further purification processing steps in addition to filtration steps, including chromatography, to further purify the adenovirus particles (at least p. 11-14).
Regarding instant claim 78, De Vocht et al. teach adenovirus particles (a biological product) recovered from lysed host cells (at least p. 20-24, example 3-4).
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.
Claims 59-78 are rejected under 35 U.S.C. 103 as being unpatentable over De Vocht et al. (WO 2011045381) in view of Cytiva (2020 Scalable process for adenovirus production sheets: 13 pages). The teachings of De Vocht et al. over at least instant claims 59-60, 64, 75-76, 78 are noted above.
De Vocht et al. also disclose a method for selective host cell DNA precipitation in high cell density, comprising lysing host cells by adding nonionic detergents Triton X-100 and Tween-80 to final concentrations 0.1 and 0.05%, respectively, adding 0.063% and 0.077% domiphen bromide in 40 mM NaCl to the lysed harvest, clarifying the precipitated lysate by tangential flow filtration to remove large cell debris, impurities and precipitated DNA, from the virus-containing suspension (at least p. 22, example 4). De Vocht et al. disclose further purification processing steps in addition to filtration steps, including chromatography, to further purify the adenovirus particles (at least p. 11-14). De Vocht et al. do not explicitly teach a NaCl concentration of at least 100 mM.
Cytiva also discloses a process for adenovirus production. Cytiva discloses further downstream purification steps to recover the adenovirus particles (at least p. 1-2). Cytiva discloses that concentration and buffer exchange by tangential flow filtration (TFF) was conducted for further reduction of impurities and buffer exchange into 20 mM Tris, pH 8.0 + 300 mM NaCl, 2 mM MgCl2, to prepare the adenovirus-containing sample for subsequent downstream purification steps; for maintaining virus stability, MgCl2 was added to all buffers from the first TFF step and onwards (at least p. 2).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to further incorporate the 300 mM NaCl and MgCl2 salts of Cytiva into the adenovirus-containing suspension prior to further downstream processing steps in the method of De Vocht et al. noted above (instant claims 59, 64-65). The motivation to do is given by Cytiva, which discloses that incorporating 300 mM NaCl, 2 mM MgCl2 salts prepares adenovirus-containing suspensions for further downstream processing steps. One of ordinary skill would have a reasonable expectation of success because the prior art discloses the same method steps and conditions for selectively precipitating and/or removing host cell DNA to recover adenovirus particles.
Additionally, regarding instant claims 64-65, since Cytiva discloses addition of 300 mM NaCl, 2 mM MgCl2 salts, Cytiva can be deemed to disclose a sufficient concentration that inhibits DNA precipitation.
Regarding instant claim 66, as noted above, Cytiva discloses that including 300 mM NaCl, 2 mM MgCl2 salts prepares adenovirus-containing suspensions for subsequent downstream purification steps, including chromatography steps (p. 2-3). “[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). MPEP 2144.05. Therefore, it would have been obvious to one of ordinary skill in the art to arrive at other working concentrations for the MgCl2 salt, including the recited at least 10 mM, for preparing the adenovirus-containing suspension for additional downstream purification steps, by routine optimization.
Regarding instant claim 61, De Vocht et al. disclose a harvested cell density between 20-30 x 106 cells/mL and adding nonionic detergents Triton X-100 and Tween-80 to final concentrations of respectively 0.1% and 0.05% (p. 23 example 4). De Vocht et al. further disclose that it is clear to the person skilled in the art that the optimal concentration of the detergent may vary, for instance within the range of about 0.1%-1% (w/w) (p. 6 lines 4-17). As already noted, “[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). MPEP 2144.05. Therefore, it would have been obvious to one of ordinary skill in the art to arrive at the recited final concentration of the detergent of at least 0.3% by routine optimization.
Regarding instant claims 62-63, De Vocht et al. disclose precipitating host DNA with 0.063% to 0.77% of domiphen bromide (DB) in the lysate (p. 23 example 4). De Vocht et al. disclose DB concentrations for treating adenovirus containing high cell density suspensions comprising a cell density ranging between 10 x 106 and 150 x 106 cells/mL ranges between 1.2 mM to 5 mM (p. 8-9). Therefore, it would have been obvious to one of ordinary skill in the art to arrive at the recited final concentration of DB of at least 0.15% by routine optimization and a concentration of not less than 0.007% for a cell density 10 x 106 cells/mL by routine optimization.
Regarding instant claims 67-74, as noted above, De Vocht et al. has disclosed a method for selective host cell DNA precipitation in high cell density between 20-30 x 106 cells/mL, comprising lysing host cells by adding nonionic detergents Triton X-100 and Tween-80 to final concentrations 0.1 and 0.05%, respectively, adding 0.063% and 0.077% domiphen bromide in 40 mM NaCl to the lysed harvest, clarifying the precipitated lysate by tangential flow filtration to remove large cell debris, impurities and precipitated DNA, from the virus-containing suspension (at least p. 22, example 4). Vocht et al. disclose DB concentrations for treating adenovirus containing high cell density suspensions comprising a cell density ranging between 10 x 106 and 150 x 106 cells/mL ranges between 1.2 mM to 5 mM (p. 8-9). De Vocht et al. further disclose that it is clear to the person skilled in the art that the optimal concentration of the detergent may vary, for instance within the range of about 0.1%-1% (w/w) (p. 6 lines 4-17). As also noted above, Cytiva discloses including salts 300 mM NaCl, 2 mM MgCl2 to prepare the adenovirus-containing sample for subsequent downstream purification steps and maintaining virus stability by adding MgCl2 to all buffers from the first TFF and onwards. Therefore, it would have been obvious to one of ordinary skill to arrive at the conditions recited in the instant claims 67-74, including 10x106 cells/mL, detergent concentrations including at least 0.3%, DB concentrations including at least 0.15%, NaCl concentrations including at least 100 mM, MgCl2 concentrations including at least 10 mM, and a concentration of not less than 0.007% DB for a cell density 10 x 106 cells/mL, by routine optimization, in the method for selectively precipitating and/or removing host cell DNA to recover adenovirus particles of De Vocht et al. in view of Cytiva because the prior art discloses the same method steps and similar conditions for recovering adenovirus particles.
Regarding instant claim 77, De Vocht et al. disclose further purification processing steps in addition to filtration steps, including combinations of various chromatography steps, to further purify the adenovirus particles (at least p. 11-14) and Cytiva also discloses a combination of chromatography steps (at least p. 2-4). De Vocht et al. disclose adenovirus recovery of greater than 80% and 100% precipitation of host cell DNA (p. 23) and Cytiva also discloses host cell DNA levels below levels of detection (p. 8). Therefore, one of ordinary skill would have a reasonable expectation of success that the method for selectively precipitating and/or removing host cell DNA to recover adenovirus particles of De Vocht et al. in view of Cytiva, including further purification processing steps including combinations of various chromatography steps, to further purify the adenovirus particles, is effective to produce adenovirus particles at the recited yield of at least 50% after a plurality of chromatography steps, including the recited 5 chromatography cycles.
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Marsha Tsay whose telephone number is (571)272-2938. The examiner can normally be reached M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath N. Rao can be reached at 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Marsha Tsay/Primary Examiner, Art Unit 1656