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 .
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The IDS received on March 17, 2023 and May 8, 2023 are proper and are being considered by the Examiner.
The NPL #10-13, cited in the IDS received on March 17, 2023 have not been provided in the parent nor in the present application. Therefore, they have been lined-through.
Drawings
The drawings received on March 17, 2023 are acceptable.
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.
Claims 1-9 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.
Claim 1 recites the phrase, “the isolated blood cell populations”. There is an insufficient antecedent basis for this limitation in the claim. For the purpose of prosecution, the phrase has been construed to mean, “the enriched blood cell populations”.
Claims 2-9 are indefinite by way of their dependency on claim 1.
Claim Rejections - 35 USC § 102
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 1-3 and 9 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Leiby et al. (WO 96/13615 A1, published May 1996).
With regard to claim 1, Leiby et al. teach that pathogens are parasitic microbes that cross cell barriers and dwell within cells, particularly body fluid cells and this without destroying the host cells (“[i]ntracellular pathogens are parasitic microbes that cross cell barriers and dwell within cells, particularly body fluid cells, for extended periods of time without destroying the host cells”, page 1, lines 13-15).
Lieby et al. teach an enrichment of such cells which harbor pathogen therein, including but not limited to monocytes, lymphocytes, erythrocytes, etc.:
“invention encompasses flow cytometric methods capable of detecting intracellular pathogens in cells at extremely low levels of infection. The invention provides methods for accurate detection of pathogen infected cells in blood (red blood cells, monocytes, lymphocytes, polymorphonuclear leukocytes), bone marrow, and other tissues and body fluids” (page 11, lines 4-8)
In the enrichment process of these cells, Leiby et al. teach the use of flow cytometry which sorts the desired cells that are labeled (see page 6, lines 23-29; page 7, lines 1-11).
Leiby et al. employs the flow cytometry sorting process to enrich for cells which are infected with pathogens and thus do not rely on centrifugation:
“There are a number of ways to enhance the sensitivity and specificity of the flow cytometry detection technique. These include, but are not limited to, labeling the cell preparation for both characteristic cell surface antigens and the intracellular pathogen to improve the frequency of incidents … One can gate the cell cytometry machine to specifically select only monocytes and macrophages in a cell population, thereby reducing the number of cells examined in the assay” (page 7, line 30 to page 8, line 10)
Lieby et al. also teach the presence of the pathogens in the enriched blood cell populations (“[w]e initially identified infected cells by … fluorescence labeled secondary antibody … used to identify the primary antibody specific for the pathogen”, page 20, lies 15-18).
With regard to claims 2 and 3, while the cell fragments and exosomes are listed as an alternative source of the specific blood cell populations, they are not actively required in the claims.
With regard to claim 9, the target pathogen is bacterial (Leishmania, see page 21, line 4), or viral (HIV, see page 21, line 28).
Therefore, Leiby et al. anticipate the invention as claimed.
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.
Claims 4-8 are rejected under 35 U.S.C. 103 as being unpatentable over Leiby et al. (WO 96/13615 A1, published May 1996) in view of Swennenhuis et al. (Genome Medicine, 2013, vol. 5, pages 1-11).
The teachings of Leiby et al. have already been discussed above.
Leiby et al. do not teach the detection of the pathogens in the enriched blood sample by assaying their nucleic acid contents, and therefore, do not teach that the detection means involve PCR (claim 4), multiplex PCR (claim 5), isothermal amplification (claim 6), such as LAMP (claim 7), or hybridization assay (claim 8).
Swennenhuis et al. teach and evidence the maturation of the diagnostic field, wherein the artisans teach sample cells which have been sorted via FACS and amplifying the nucleic acids of the sorted cell population:
“ability to isolate and amplify DNA from the individual CTC [circulating tumor cells] would overcome some of these challenges. We evaluated the feasibility of DNA amplification after fluorescence-activated cell sorting (FACS) of CTC obtained …” (page 2, 1st column)
In doing so, the artisans sort the desired cell population via cell sorting (FACS) and amplify the contents therein via isothermal amplification (“[a]fter sorting, the wells were treated proteinase K … After this step, 5 ml of an amplification mix containing Evagreen, a double-stranded DNA dye … was added … amplification mix consisted of components from GE Illustra Genomic Phi DNA amplification kit1”, page 2, 2nd column, bottom paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Leiby et al. with the teachings of Swennenhuis et al. and the conventionally available kits in the art, thereby arriving at the invention as claimed for the following reasons.
As discussed above, Leiby et al. teach that presence of pathogens in small amounts of cell in a sample can be efficiently and specifically detected by enriching for the cells via fluorescence labeled cell sorting and detecting for the presence of the pathogens therein. While the artisans did not explicitly teach the isolation of the pathogens’ nucleic acid for the detection means, involving PCR, LAMP, or multiplex PCR, one of ordinary skill in the art would have been motivated to assay for the nucleic acid contents of the pathogen to further identify the presence and identity of the pathogens present in the cells based on the teachings provided by Swennenhuis et al. who also state that low amounts of cells present in a sample can first be enriched by cell sorting, and their contents detected via nucleic acid amplification.
By doing so, one of ordinary skill in the art would have recognized that benefit of not only detecting the presence or absence of the pathogens or virus (HIV) in the enriched cell population of Leiby et al., but also the identity information of such pathogens, such as their strains, which would have been useful.
And while Swennenhuis et al. disclosed only one particular type of an amplification reaction widely adopted in the art (i.e., isothermal amplification), having been motivated to sort the cells and amplify the nucleic acids therein, one of ordinary skill in the art would have recognized that any prior art known means of amplifying the nucleic acids, such as PCR, multiplex PCR, of LAMP, or array hybridization, all of which have been well established in the art, would have yielded a predictable outcome of yielding nucleic acid sequence information of pathogens being assayed for.
In KSR, the Supreme Court particularly emphasized “the need for caution in granting a patent based on the combination of elements found in the prior art,” Id. at 415, 82 USPQ2d at 1395, and discussed circumstances in which a patent might be determined to be obvious. Importantly, the Supreme Court reaffirmed principles based on its precedent that “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” Id. at 415-16, 82 USPQ2d at 1395. The Supreme Court stated that there are “[t]hree cases decided after Graham [that] illustrate this doctrine.” Id. at 416, 82 USPQ2d at 1395. (1) “In United States v. Adams, . . . [t]he Court recognized that when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable result.”
Therefore, the invention as claimed is deemed prima facie obvious over the cited references.
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 1-9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of U.S. Patent No. 11,629,374 (herein, “the ‘374 patent”).
Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons.
With regard to instant claims 1-3, claims of the ‘374 patent also claims a method of collecting a whole blood sample, enriching for specific blood cell populations without centrifugation, involving particle size; and specifically detecting the target pathogens in the isolated blood populations (see claim 1).
With regard to claims 4, 5, and 9, claims 2-4 are verbatim.
Claims of the ‘374 patent do not claim other types of nucleic acid amplification or assays for detecting the pathogen nucleic acids, such as isothermal amplification, LAMP, or hybridization assay (claims 6-8).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the claims of the ‘374 patent with the teachings conventionally available kits in the art, thereby arriving at the invention as claimed for the following reasons.
As discussed above, claims of the ‘374 patent already claim a method that detects target pathogens in whole blood by first enriching for specific blood cell populations by means of particle size while not involving centrifugation, and then detecting the nucleic acids therein by an amplification reaction, such as PCR and multiplex PCR.
While the ‘374 patent did not explicitly claim all possible types amplification means known in the art, one of ordinary skill in the art would have recognized that any prior art known means of amplifying the nucleic acids, such as PCR, multiplex PCR, of LAMP, or array hybridization, all of which have been well established in the art, would have yielded a predictable outcome of yielding nucleic acid sequence information of pathogens being assayed for.
In KSR, the Supreme Court particularly emphasized “the need for caution in granting a patent based on the combination of elements found in the prior art,” Id. at 415, 82 USPQ2d at 1395, and discussed circumstances in which a patent might be determined to be obvious. Importantly, the Supreme Court reaffirmed principles based on its precedent that “[t]he combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results.” Id. at 415-16, 82 USPQ2d at 1395. The Supreme Court stated that there are “[t]hree cases decided after Graham [that] illustrate this doctrine.” Id. at 416, 82 USPQ2d at 1395. (1) “In United States v. Adams, . . . [t]he Court recognized that when a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable result.”
Conclusion
No claims are allowed.
Inquiries
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to Young J. Kim whose telephone number is (571) 272-0785. The Examiner can best be reached from 7:30 a.m. to 4:00 p.m (M-F). The Examiner can also be reached via e-mail to Young.Kim@uspto.gov. However, the office cannot guarantee security through the e-mail system nor should official papers be transmitted through this route.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner's supervisor, Gary Benzion, can be reached at (571) 272-0782.
Papers related to this application may be submitted to Art Unit 1681 by facsimile transmission. The faxing of such papers must conform with the notice published in the Official Gazette, 1156 OG 61 (November 16, 1993) and 1157 OG 94 (December 28, 1993) (see 37 CFR 1.6(d)). NOTE: If applicant does submit a paper by FAX, the original copy should be retained by applicant or applicant’s representative. NO DUPLICATE COPIES SHOULD BE SUBMITTED, so as to avoid the processing of duplicate papers in the Office. All official documents must be sent to the Official Tech Center Fax number: (571) 273-8300. Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-1600.
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.
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/YOUNG J KIM/Primary Examiner
Art Unit 1637 September 30, 2025
/YJK/
1 The kit is commercially sold and known for isothermally amplifying whole genome.