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. Claims 18-35, of record 12/18/2023, are pending and subject to prosecution. Priority The instant application is a national stage entry of PCT/CN2021/134470 (filed 11/30/2021). Acknowledgement is made of the applicant’s claim for foreign priority to application 202110676917.3 (filed 6/18/2021 in China). Specification The use of the term s KrosFlo , AceQ , and Triton , which are trade name s or mark s used in commerce, has been noted in this application. The term s should be accompanied by the generic terminology; furthermore , the term s should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term s . 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 Objections Claim 31 is objected to because of the following informalities: In claim 31, the abbreviations BSA, HCP, and HCD should be written out fully . Appropriate correction is required. Claim Interpretation Claim 30 recit es a retrovirus obtained by the method of claim 1 8 . The retrovirus is defined using product-by-process limitations. Product-by-process claims are considered only in so far as the method of production imparts distinct structural or chemical characteristics or properties to the product. Therefore, if the product as claimed is the same or obvious over a product of the prior art ( i.e. , is not structurally or chemically distinct), the claim is considered unpatentable over the prior art, even though the prior art product is made by a different process. See MPEP 2113. In the instant application, because the method of claim 1 8 does not distinguish the retrovirus from retrovirus generated by other methods, the retrovirus is interpreted as comprising any purified retrovirus . 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 appl icant regards as his invention. Claim s 33 and 35 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. Claims 33 and 35 are drawn to a method for preparing a therapeutic product but fail to recite any active steps for executing the method. The claims are indefinite because they attempt to claim a process without setting forth any steps involved in the process. 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 s 30-32 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception ( i.e. , a law of nature, a natural phenomenon, or an abstract idea) without significantly more. The claims have been analyzed for eligibility in accordance with their broadest reasonable interpretation. Regarding claims 30-3 1 : Claims 30-3 1 are directed to a retrovirus and a retrovirus wherein the BSA is <200 ng/ml, HCP is <1 µg/ml, and HCD is <100 ng/ml, respectively. The amounts of BSA, HCP, and HCD do not alter the structural properties of the retrovirus. The broadest reasonable interpretation of the claimed retrovirus is therefore considered to encompass any retrovirus. Step 1: Each claim is directed to a retrovirus , which is a statutory category of matter (Step 1: YES). Step 2A, prong 1: Retroviruses are nature-based products. When a claimed composition includes a nature-based product, further analysis is taken to determine if the claimed composition recites a nature-based product judicial exception by comparing the claimed composition to the closest naturally occurring counterpart to determine if the claimed composition has markedly different characteristics than the counterpart. The closest naturally occurring counterpart of a retrovirus is a naturally occurring retrovirus (See Weiss, Abstract and page 1, ¶ 1). The claimed retrovirus read s on naturally occurring retrovirus . Thus, the retrovirus is considered to read on a product of nature judicial exception (Step 2, prong 1: YES) . Step 2A, prong 2: Each claim is directed to a product and does not recite any structure that serves to integrate the compositions into a practical application (Step 2, prong 2: NO). Step 2B: There are no additional elements required by the claims. Claims 30-31 do not qualify as eligible subject matter and are rejected under 35 U.S.C. 101. Regarding claim 32 : Claim 32 is directed to a product wherein the product contains the retrovirus of claim 30. The product is not limited in any way, apart from containing the retrovirus of claim 30, which itself is interpreted as encompassing any retrovirus. The broadest reasonable interpretation of the claimed product, which lacks any other limitations, is therefore also considered to encompass any retrovirus. Step 1: The claim is directed to a retrovirus , which is a statutory category of matter (Step 1: YES). Step 2A, prong 1: Retroviruses are nature-based products. When a claimed composition includes a nature-based product, further analysis is taken to determine if the claimed composition recites a nature-based product judicial exception by comparing the claimed composition to the closest naturally occurring counterpart to determine if the claimed composition has markedly different characteristics than the counterpart. The closest naturally occurring counterpart of a retrovirus is a naturally occurring retrovirus (See Weiss, Abstract and page 1, ¶ 1). The claimed retrovirus read s on naturally occurring retrovirus . Thus, the retrovirus is considered to read on a product of nature judicial exception (Step 2, prong 1: YES) . Step 2A, prong 2: The claim is directed to a product and does not recite any structure that serves to integrate the compositions into a practical application (Step 2, prong 2: NO). Step 2B: There are no additional elements required by the claim. Claim 32 do es not qualify as eligible subject matter and is rejected under 35 U.S.C. 101. 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. (a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention. Claim s 30-33 and 35 are rejected under 35 U.S.C. 102 (a)(1) and 102(a)(2) as being anticipated by Shi et al. (CN 111876393 A , machine translation ) , of record in IDS dated 12/18/2023 . Shi et al. teach the large-scale purification of lentiviral vectors from cell culture supernatants (See Abstract). Regarding claims 30, 32-33, and 35: Shi et al. teach a method for purifying lentivirus (which reads on “retrovirus”, “product”, and “therapeutic product”) for gene therapy through multiple filtration, digestion, and chromatography steps (See page 4, ¶ 2-8 and page 5, ¶ 6). Thus, Shi et al. disclose a purified retrovirus. Regarding claim 31: Following the discussion of claims 30, 32-33, and 35, Shi et al. teach that that the purified virus samples contained 0 ng/ml BSA, 17.30 ng/ml HCP or less, and 8.65 ng/ml HCD or less (See table 1). Claims 30 and 32 -33 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Bowles et al. (Human Gene Therapy, 1996). Regarding claims 30 and 32-33: Bowles et al. teach purification of retroviral vectors for therapeutic use (See Abstract). Thus, Bowles et al. disclose a purified retrovirus, a therapeutic product, and a method of preparing the therapeutic product. Claims 30 and 32 -33 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Cruz et al. (Viral Vectors for Gene Therapy, 2011). Regarding claims 30 and 32-33: Cruz et al. teach purification of retroviral vectors for clinical applications (See Abstract). Thus, Cruz et al. disclose a purified retrovirus, a therapeutic product, and a method of preparing the therapeutic product. Claim 33 is rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by Hoffmann (US 644077 A). Regarding claim 33: Hoffmann teaches a method for the production of acetylsalicylic acid (which reads on “a therapeutic product”) (See page 1, col. 1-2). 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. 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. Claim s 18 -22, 24, and 28 -35 are rejected under 35 U.S.C. 103 as being unpatentable over Shi et al. (CN 111876393 A) , of record, in view of Bowles et al. (Human Gene Therapy, 1996) . The teachings of Shi et al. are set forth in the rejection above and are incorporated herein in their entirety. Regarding claims 18-22, 24, and 28-35 : Shi et al. teach a method for purifying lentivirus (which reads on “retrovirus”, “product”, and “therapeutic product”) for gene therapy through multiple filtration, digestion, and chromatography steps (See page 4, ¶2-8 and page 5, ¶6). Shi et al. teach that t he virus-containing supernatant is initially clarified by filtration (which reads on “performing a microfiltration of a cell culture supernatant to remove cell debris”) (See page 4, ¶ 4 ). A 0.45 µm or 0.65 µm glass fiber filter (which reads on “a membrane pore size… of the semipermeable membrane used is 0.45 µm-0.75 µm”) can be used for clarification (See page 4, ¶ 10). The clarified supernatant is concentrated by ultrafiltration and treated with a nuclease (which reads on “performing a treatment… with a nuclease to degrade host DNA residues into small DNA fragments”) (See page 4, ¶ 5 ). The nuclease treatment is preferably performed at 2-8°C for 12-24 h (which reads on 2 ° C to 8 ° C for 8 h to 24 h”) with 5-200 IU/ml (which reads on “1 U·mL -1 to 500 U·mL -1 ”) of a totipotent nuclease (See page 4, ¶ 13). Ultrafiltration is preferably performed with a 100-500 kD MWCO membrane (which reads on “350 to 750 KD”) (See page 4, ¶ 12 ). A sterilization step, comprising filtration through a 0.22 µm pore size membrane and rinsing with sterile buffer, can follow (See page 5, ¶ 3). Thus, Shi et al. disclose a purified retrovirus. Shi et al. further teach that that the purified virus samples contained 0 ng/ml BSA, 17.30 ng/ml HCP or less, and 8.65 ng/ml HCD or less (See table 1). Shi et al. do not expressly teach nuclease treatment prior to ultracentrifugation as required in claim 18 step B , however , selection of any order of process steps is considered to be prima facie obvious in the absence of new or unexpected results. See MPEP 2144.04(IV)(C). Shi et al. also do not teach low-spee d precipitation of the virus , as required in step D of claim 18 . Bowles et al. teach sedimentation of retroviral vectors by centrifugation at 6000 × g (which reads on “low speed”) for 16 h at 4°C (See page 1736, col. 2, full ¶ 3 and page 1738, col. 1, ¶ 1). It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Shi et al. to comprise a step of pelleting the retrovirus by low-speed centrifugation, such as is taught by Bowles et al. One would be motivated to make this modification because Bowles et al. teach that the pelleted virus can be resuspended in greater than 1% of the starting volume, or concentrated almost 100-fold (See page 1738, col. 1, ¶ 1 ). A skilled artisan would have had a reasonable expectation of success because such a step could be readily incorporated into the method of Shi et al . Claims 18-22, 24-25, and 27-35 are rejected under 35 U.S.C. 103 as being unpatentable over Shi et al. (CN 111876393 A) , of record, in view of Bowles et al. (Human Gene Therapy, 1996), further in view of Cruz et al. (Viral Vectors for Gene Therapy, 2011). The teachings of Shi et al. and Bowles et al. are set forth in the rejection s above and are incorporated herein in their entirety. Regarding claims 25 and 27: Following the discussion of claims 18-22, 24, and 28-35, Shi et al. , modified by Bowles et al. , render obvious a method for purifying retrovirus but do not expressly teach microfiltration flow rate or temperature. Cruz et al. teach protocols for manufacturing retroviruses (See Abstract). A microfiltration step comprising filtering supernatant is carried out at a flow rate of 100-300 ml/min (See page 170, 3.3.2.1.2). Cruz et al. also recommend that the purification protocol is performed at 4-6°C (See page 169, 3.3.2.). It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Shi et al. , modified by Bowles et al. , to comprise the microfiltration rate and temperature taught by Cruz et al. for purifying retrovirus. One would be motivated to make these modifications because Cruz et al. teach that a low purification temperature maintains viral stability and achieves higher transducing unit yields and that the steps of their protocol are suitable for retroviruses (See page 169, 3.3.2 ). A skilled artisan would have had a reasonable expectation of success because use of microfiltration and low temperature in methods of purifying retroviruses was known at the time of the invention and could readily be incorporated into the method of Shi et al. , modified by Bowles et al. Claims 18-22 and 24-35 are rejected under 35 U.S.C. 103 as being unpatentable over Shi et al. (CN 111876393 A) in view of Bowles et al. (Human Gene Therapy, 1996), further in view of Cruz et al. (Viral Vectors for Gene Therapy, 2011), further in view of Venereo -Sanchez et al. ( Vaccine, 2017 ). The teachings of Shi et al. , Bowles et al. , and Cruz et al. are set forth in the rejections above and are incorporated herein in their entirety. Regarding claim 26: Following the discussion of claims 18-22, 24-25, and 27-35, Shi et al. , modified by Bowles et al. and Cruz et al. , render obvious a method for purifying retrovirus but do not expressly teach a shear rate for microfiltration. Venereo -Sanchez et al. teach the production and purification of HIV Gag-based virus-like particles (See Abstract). The VLPs were filtered at a shear rate of approximately 2000 s -1 (See page 4227, col. 1, full ¶ 1). It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Shi et al. , modified by Bowles et al. and Cruz et al. , to comprise retrovirus filtration at a shear rate of approximately 2000 s -1 , as taught by Venereo -Sanchez et al. One would be motivated to make this modification because Venereo -Sanchez et al. teach that both enveloped viruses and VLPs are sensitive to shear stress (See page 4227, col. 1, full ¶ 1) . There would be a reasonable expectation of success in doing so because of the structural similarity between Gag-based VLPs and native retrovirus and because the shear rate of the method could be readily adjusted. Allowable Subject Matter Claim 23 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. The following is a statement of reasons for the indication of allowable subject matter: The prior art does not teach retroviral purification wherein a microfiltration step comprises filtration in a 750 kD MWCO hollow fiber filter having a membrane area of 0.16 m 2 and a fiber diameter of 0.5 mm with a shear rate of 2000 s -1 followed by filtration in a 750 kD MWCO hollow fiber filter having a membrane area of 0.0115 m 2 and a fiber diameter of 0.5 mm with a shear rate of 2000 s -1 . Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to FILLIN "Examiner name" \* MERGEFORMAT JENNIFER S SPENCE , whose telephone number is FILLIN "Phone number" \* MERGEFORMAT 571-272-8590 . The examiner can normally be reached FILLIN "Work Schedule?" \* MERGEFORMAT M-F 8:30-5:30 . 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, FILLIN "SPE Name?" \* MERGEFORMAT Christopher M Babic , can be reached at FILLIN "SPE Phone?" \* MERGEFORMAT 571-272-8507 . 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. /J.S.S./ Examiner, Art Unit 1633 /CHRISTOPHER M BABIC/ Supervisory Patent Examiner, Art Unit 1633