CTNF 18/854,293 CTNF 82966 DETAILED ACTION Notice of Pre-AIA or AIA Status 07-03-aia AIA 15-10-aia 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 08-25-01 AIA Applicant’s election without traverse of Group I in the reply filed on 5/12/26 is acknowledged. Specification 07-29 AIA The disclosure is objected to because of the following informalities: In the first paragraph, the priority information should be set forth. In the detailed description, figures 19, 20A-F, and 22 should be described . Appropriate correction is required. Claim Objections 07-29-01 AIA Claim 6 is objected to because of the following informalities: In claim 6, lines 5, 6, and 8, reference to the container, surface, and period should be ‘the sealable container’, ‘the bottom surface’, and ‘the period’, respectively. These terms are previously introduced . Appropriate correction is required. Claim Rejections - 35 USC § 102 07-07-aia AIA 07-07 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 – 07-08-aia AIA (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. 07-15 AIA Claim s 1, 2, 12, 14, 17, and 19 are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Hossack et al (US Pub 2018/0099059 -cited by applicant) . Re claim 1: Hossack discloses a method comprising: introducing a labeled phagocytotic cell into a patient [0034, claim 16; see the cells labeled with PFC droplets that are introduced and ingested by target cells in a test region]; and determining a location of the labeled phagocytotic cell in the patient [0030; a location of the cells within the patient are provided with an imaging system]. Re claim 2: The method includes labeling a phagocytotic cell with an echogenic microbubble to form the labeled phagocytotic cell [0034, claim 16; see the cells labeled with PFC droplets that are introduced and ingested by target cells in a test region]; and isolating the phagocytotic cell from the patient [0030; the cells can be isolated cells such as dendritic cells, macrophages, T-cells, B-cells]. Re claim 12: The method includes labeling a phagocytotic cell with an echogenic microbubble to form the labeled phagocytotic cell [0034, claim 16; see the cells labeled with PFC droplets that are introduced and ingested by target cells in a test region]; and characterizing a trafficking pattern of the labeled phagocytotic cell; wherein the determining comprises ultrasound imaging the patient to determine the location of the labeled phagocytotic cell in the patient [0030, 0031; see the imaging and that the droplets are used to track the movement of phagocytotic cells]. Re claim 14: The method includes introducing comprises introducing labeled phagocvtotic cells into the patient [0034, claim 16; see the cells labeled with PFC droplets that are introduced and ingested by target cells in a test region]; the determining comprises determining the location of the labeled phagocytotic cells in the patient [0030; a location of the cells within the patient are provided with an imaging system]; and the method further comprises: labeling the phagocytotic cells with echogenic microbubbles [0034, claim 16; see the cells labeled with PFC droplets that are introduced and ingested by target cells in a test region]; and ultrasound imaging the patient to determine a characterization of one or more trafficking patterns of the labeled phagocytotic cells [0030, 0031; see the ultrasound imaging and tracking the cells]; wherein the characterization comprises one or more of: determining accumulation of the labeled phagocytotic cells [0030, 0031; wherein the imaging determined how much is accumulated]; determining a flux of the labeled phagocytotic cells [0031; the droplets are used to track movement of the cells to and from the organ or region of injection]; or determining a distribution of the labeled phagocytotic cells [0030, 0034; see the tracking of different B-cell types]. Re claim 17: The phagocytotic cells comprise macrophages [0030; see the macrophages]. Re claim 19: The echogenic microbubbles comprise a fluorocarbon compound in a lipid shell [0022, 0045; see the lipid shell with PFC] . Claim Rejections - 35 USC § 103 07-20-aia AIA 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. 07-21-aia AIA Claim s 3 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Hossack, as applied to claim 1, in view of “Union” (CN 111569092 -cited by applicant) . Re claims 3, 4: Hossack discloses all features including labeling and that the determining comprises ultrasound imaging [0030, 0034, claim 16; see the labeling and ultrasound imaging] but does not disclose: placing the phagocytotic cell in a solution comprising the echogenic microbubble, the solution contained in a sealable container; fixing the phagocytotic cell to a bottom surface of the sealable container; sealing the sealable container; inverting the sealable container; incubating the phagocytotic cell for4 hours; and washing the phagocytotic cell. However, Union teaches placing the phagocytotic cell in a solution comprising the echogenic microbubble, the solution contained in a sealable container; fixing the phagocytotic cell to a bottom surface of the sealable container; sealing the sealable container; inverting the sealable container; incubating the phagocytotic cell for 4 hours; and washing the phagocytotic cell (page 9 paragraph 5; page 10 paragraphs 6 & 8; see the agent that is co-incubated for 2 to 12 hours with macrophages, PBS is washed 3 times, cells are scraped, and new agents are collected by washing, wherein droplets are composed of inert compound perfluorocarbon which will be vaporized into microbubbles). It would have been obvious to the skilled artisan to modify Hossack, to label as taught by Union, in order to label cells with microbubbles in order to track the labeled cellos using ultrasound imaging. Further, incubating the cell at approximately 100 degrees Fahrenheit . 07-21-aia AIA Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Hossack/Union, as applied to claim 3, in view of Toma et al (US Pub 2011/0208113 -cited by applicant) . Re claim 6: Hossack discloses the echogenic microbubble is one of a plurality of echogenic microbubbles; the phagocytotic cell is one of a plurality of phagocytotic cells [0031; see the tracking of the phagocytotic cells]; and Union teaches the placing comprises placing the plurality of phagocytotic cells in a solution comprising the plurality of echogenic microbubbles, the solution contained in a sealable container; the fixing comprises fixing the plurality of phagocytotic cells to a bottom surface of the sealable container; the incubating comprising incubating the plurality of phagocytotic cells for a period of time (page 9 paragraph 5; page 10 paragraphs 6 & 8; see the agent that is co-incubated for 2 to 12 hours with macrophages, PBS is washed 3 times, cells are scraped, and new agents are collected by washing, wherein droplets are composed of inert compound perfluorocarbon which will be vaporized into microbubbles). Hossack/Union do not teach the solution comprises a ratio of phagocytotic cells to echogenic microbubbles of between approximately 1:1 and 1:50. However, Toma teaches the solution comprises a ratio of phagocytotic cells to echogenic microbubbles of between approximately 1:1 and 1:50 [0318, 0319; see the cells mixed with increasing ratios of cationic microbubbles such as 1:1 or 1:40]. It would have been obvious to the skilled artisan to modify Hossack/Union, to use the ratio as taught by Toma, in order to facilitate tracking using ultrasound imaging . 07-21-aia AIA Claim 13 is rejected under 35 U.S.C. 103 as being unpatentable over Hossack, as applied to claim 1, in view of Hendrick et al (US Pub 2021/0340218 -cited by applicant) . Re claim 13: Hossack discloses the introducing comprises introducing labeled phagocvtotic cells into the patient [0034, claim 16; see the cells labeled with PFC droplets that are introduced and ingested by target cells in a test region]; the determining comprises determining the location of one or more of the labeled phagocytotic cells in the patient [0030; a location of the cells within the patient are provided with an imaging system]; and the method further comprises: labeling the phagocvtotic cells with one or more echogenic microbubbles to form the labeled phagocvtotic cells; and characterizing one or more trafficking patterns of the labeled phagocytotic cells in the patient over a time period, the characterizing comprising: detecting one or more of the labeled phagocytotic cells in a patient with the SNR > 5;discriminating at least a portion of the labeled phagocytotic cells from background cells; resolving one or more single respective labeled phagocytotic cells from among the labeled phagocytotic cells using a spatial resolution equal to or better than 20 m; and imaging the target anatomy with a FOV on the order of one or more centimeters the determining comprises determining the location of the labeled phagocytotic cells in the patient [0030, 0031, 0034, claim 16; see the labeling, tracking, and ultrasound imaging that includes detecting at a SNR > 5 and spatial resolution better than 20 microns]. Hossack does not disclose determining a respective velocity of at least a portion of the respective resolved single labeled phagocytotic cells, wherein a low velocity correlates with a strength of an interaction of the respective resolved single labeled phagocytotic cell with a target anatomy. However, Hendrick teaches determining a respective velocity of at least a portion of the respective resolved single labeled phagocytotic cells, wherein a low velocity correlates with a strength of an interaction of the respective resolved single labeled phagocytotic cell with a target anatomy [0155, figure 1B; see the patrolling speed and number of Nur77-GFPhigh monocytes]. It would have been obvious to the skilled artisan to modify Hossack, to determine velocity as taught by Hendrick, in order to indicate the strength of interaction between the phagocytotic cell and the target anatomy . 07-21-aia AIA Claim s 18, 23, 24, 39, 40, 45, and 46 are rejected under 35 U.S.C. 103 as being unpatentable over Hossack or Hossack/Hendrick, further in view of Hong et al (US Pub 2019/0307794 -cited by applicant) . Re claims 18, 23, 24, 39, 40, 45, 46: Hossack or Hossack/Hendrick disclose all features including labeling and introducing the cells and ultrasound imaging to determine locations and trafficking patterns, and echogenic microbubbles comprises a fluorocarbon compound in a shell selected from group consisting of a lipid shell and a mannose shell [0030, 0034, 0045, claim 16; see the labeling and ultrasound imaging and also see the droplets converted to microbubbles in a controlled manner with a lipid shell] except that the phagocytotic cells comprise bone marrow-derived macrophages, performing cell engineering on the phagocytotic cells, isolating at least a portion of the labeled phagocytotic cells from the patient, wherein echogenic microbubbles comprises a fluorocarbon compound in a shell selected from group consisting of a lipid shell and a mannose shell, and changing a phenotype of the phagocytotic cells [0084, 0130; see the treating the M2 macrophage with the exosomes in vitro and see the changing of the phenotype]. It would have been obvious to the skilled artisan to modify Hossack or Hossack/Hendrick, in order to produce a phagocytotic cell with a desired phenotype . 07-21-aia AIA Claim s 20-22 and 42 are rejected under 35 U.S.C. 103 as being unpatentable over Hossack or Hossack/Hendrick/Hong, further in view of Nagy et al (US Pub 2013/0129635 -cited by applicant) . Re claims 20-22, 42: Hossack or Hossack/Hendrick/Hong disclose all features except that the compound comprises one or more of octoflouropropane and perflourobutane, wherein the echogenic microbubbles comprise a fluorocarbon compound in a mannose shell. However, Nagy teaches compound comprises one or more of octoflouropropane and perflourobutane, wherein the echogenic microbubbles comprise a fluorocarbon compound in a mannose shell [0072, 0098; see the mannose shell and fluorocarbon and perfluorocarbon gases]. It would have been obvious to the skilled artisan to modify Hossack or Hossack/Hendrick/Hong, to use the compound as taught by Nagy, in order to provide an improved contrast agent for ultrasound detection. Conclusion Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHAEL T ROZANSKI whose telephone number is (571)272-1648. The examiner can normally be reached Mon - Fri 8:00-4:00. 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, Christopher Koharski can be reached at 571-272-7230. 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. /MICHAEL T ROZANSKI/Primary Examiner, Art Unit 3797 Application/Control Number: 18/854,293 Page 2 Art Unit: 3797 Application/Control Number: 18/854,293 Page 3 Art Unit: 3797 Application/Control Number: 18/854,293 Page 4 Art Unit: 3797 Application/Control Number: 18/854,293 Page 5 Art Unit: 3797 Application/Control Number: 18/854,293 Page 6 Art Unit: 3797 Application/Control Number: 18/854,293 Page 7 Art Unit: 3797 Application/Control Number: 18/854,293 Page 8 Art Unit: 3797 Application/Control Number: 18/854,293 Page 9 Art Unit: 3797 Application/Control Number: 18/854,293 Page 10 Art Unit: 3797
Prosecution Insights