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 .
Status of the Claims
Claims 1, 2, 5-7, and 9-22 are pending. Claims 1, 2, 6, and 7 are amended. Claims 3, 4, and 8 are cancelled. Claims 9-22 are newly added. Claims 1, 2, 5-7, and 9-22 are examined herein.
Priority
The present application, filed 10/20/2023, claims benefit of U.S. Provisional Patent Application 63/418,013, filed 10/20/2022. The benefit is acknowledged and the claims examined herein are treated as having an effective filing date of 10/20/2022.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (www.omiq.ai [0073], p.14). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 1 is objected to because of the following informalities: the term “provides” in the limitation “wherein the fluorochrome-conjugated antibodies provides distinguishable fluorescence signals” is grammatically incorrect because “antibodies” is plural. The term “provides” should be amended to provide. Appropriate correction is required.
Claim 2 is objected to because of the following informalities: the punctuation “comprises;” is grammatically incorrect. The semicolon following comprises should be replaced with a colon. Appropriate correction is required.
Claim 6 is objected to because of the following informalities: the limitation “anti-CD33 antibody conjugated a fluorochrome” omits the preposition to. The limitation should be amended to recite “anti-CD33 antibody conjugated to a fluorochrome.” Appropriate correction is required.
Claim 7 is objected to because of the following informalities: the limitation “a plurality containers” omits the preposition of. The limitation should be amended to recite a “plurality of containers.” Additionally, the limitation “anti-CD33 antibody conjugated a fluorochrome” omits the preposition to. The limitation should be amended to recite “anti-CD33 antibody conjugated to a fluorochrome.” Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 6, 7, and 13-22 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. This is a new matter rejection.
Regarding claims 6 and 7, the claims recite reagent kits comprising twenty fluorochrome-antibody conjugates, wherein each fluorochrome is characterized by a specifically recited maximum emission wavelength. Particularly, the claims require fluorochromes having emission maxima at 420 nm, 450 nm, 505 nm, 547 nm, 610 nm, 515 nm, 548 nm, 575 nm, 610 nm, 667 nm, 690 nm, 710 nm, 750 nm, 781 nm, 659 nm, 668 nm, 685 nm, 720 nm, 780 nm, and 840 nm, respectively. These limitations define the fluorochromes according to particular fluorescence emission characteristics rather than limiting the reagent kits to the specific commercially identified fluorochromes disclosed in the application as originally filed.
The specification discloses fluorochromes with peak emissions occurring in different channels were identified, as well as fluorochromes that, despite sharing the same peak emission, have different spectrum ([0082], p. 15). The specification further discloses commercially available fluorochromes to be used in the flow cytometry panel are identified, covering as many possible peak emission wavelengths as possible across all available lasers ([0085], p. 16). Additionally, the specification discloses that gains of the detectors can be variable and can be set such that each fluorochrome's peak emission channel corresponds to their maximum emission wavelength and the spectral patterns do not exhibit steep changes from one channel to the next ([0086], p. 16). These disclosures establish that the originally filed specification recognizes maximum emission wavelengths as characteristics relevant to fluorochrome selection and flow cytometer configuration. However, the cited paragraphs do not identify the particular numerical maximum emission wavelengths required by claims 6 and 7, nor do they establish that the twenty fluorochrome-antibody conjugates disclosed in the application possess those exact maximum emission wavelengths.
Furthermore, Figure 10 of the drawings, expressly identifies the disclosed 20-Color AML Panel using the column headings Cytek dye, Marker, and Clone. Figure 10 identifies twenty specific commercially designated fluorochromes, including cFluor V420, cFluor V450, cFluor V505, cFluor V547, cFluor V610, cFluor B515, cFluor B548, cFluor BYG575, cFluor BYG610, cFluor BYG667, cFluor B690, cFluor BYG710, cFluor BYG750, cFluor BYG781, cFluor R659, cFluor R668, cFluor R685, cFluor R720, cFluor R780, and cFluor R840. Although the numerical suffixes of these commercial designations may correspond to the numerical wavelengths subsequently recited in claims 6 and 7, Figure 10 does not identify those suffixes as experimentally determined maximum emission wavelengths or otherwise expressly establish that the disclosed fluorochromes exhibit emission maxima at the recited wavelengths. Rather, Figure 10 identifies specific dye products and their corresponding antibody markers and clones. The distinction is material because the maximum emission wavelength of a fluorochrome is a physical fluorescence characteristic, whereas a commercial fluorochrome designation identifies a particular product. A numerical component of a commercial product designation does not, without additional supporting disclosure or evidence of the understanding of a person of ordinary skill in the art, necessarily establish the product’s precise maximum emission wavelength.
Additionally, the specification discloses a single-tube 20-color panel for AML analysis using the CYTEK NORTHERN LIGHTS™ clinical (NL-CLC) flow cytometer with increased reagent and sample efficiency ([0124], p. 24). The specification further discloses that flow cytometry kits contain specialized reagents designed for flow cytometric cellular analysis, and the kits generally contain the conjugated antibodies and fluorescent dyes directed to the research purpose of the kit ([0134], p. 26). These passages provide descriptive support for a 20-color AML panel and reagent kits containing conjugated antibodies and fluorescent dyes. However, they do not specifically describe reagent kits containing twenty fluorochrome-antibody conjugates defined by the exact maximum emission wavelengths recited in claims 6 and 7.
Importantly, the originally filed specification and drawings fail to reasonably convey possession of the claimed reagent kits comprising twenty fluorochrome-antibody conjugates characterized by the specifically recited maximum emission wavelengths. Although the specification discusses fluorochrome selection based on peak emission wavelengths, and Figure 10 identifies twenty commercially designated cFluor products, these disclosures do not establish that the inventors possessed the particular fluorochrome-antibody conjugates defined by the twenty numerical maximum emission wavelengths now recited in claims 6 and 7. Furthermore, the claims encompass fluorochromes having the specified emission maxima without limitation to the particular commercially designated fluorochromes disclosed in Figure 10. Accordingly, the disclosure of a specific commercially identified 20-color panel, together with general discussions of peak emission wavelength selection, does not reasonably convey possession of the full scope of the wavelength-defined reagent kits now claimed.
Regarding claims 13–17 and 18–22, these claims depend directly or indirectly from claims 6 and 7, respectively, and therefore incorporate the limitations requiring the twenty fluorochrome-antibody conjugates having the specifically recited maximum emission wavelengths. Although these dependent claims further specify monoclonal antibodies, staining buffers, reagent configurations, additional kit components, or commercially designated cFluor products, these additional limitations do not independently establish written-description support for the numerical maximum emission wavelengths incorporated from claims 6 and 7.
Therefore, claims 6, 7, and 13–22 fail to comply with the written description requirement of 35 U.S.C. § 112(a) because the originally filed disclosure does not reasonably convey to one of ordinary skill in the art that the inventor possessed the claimed reagent kits comprising twenty fluorochrome-antibody conjugates characterized by the specifically recited maximum emission wavelengths.
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, 2, 5, 9–12, 17, and 22 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 contains the trademark/trade name cFluor. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe fluorochromes by commercial designations rather than by sufficiently definite technical characteristics. In particular, the claim does not define the recited fluorochromes by chemical composition, molecular structure, or other independently ascertainable characteristics that would establish the boundaries of the claimed fluorochrome identities. Accordingly, the identification/description is indefinite. Appropriate correction is required.
Regarding claims 2, 5, and 9–12, these claims depend directly or indirectly from claim 1 and incorporate the same commercially designated fluorochromes. Therefore, the indefiniteness identified in claim 1 is likewise applicable to these dependent claims. Appropriate correction is required.
Regarding claims 17 and 22, the claims recite wherein the fluorochromes are cFluor V420, cFluor V450, cFluor V505, cFluor V547, cFluor V610, cFluor B515, cFluor B548, cFluor BYG575, cFluor BYG610, cFluor BYG667, cFluor B690, cFluor BYG710, cFluor BYG750, cFluor BYG781, cFluor R659, cFluor R668, cFluor R685, cFluor R720, cFluor R780, and cFluor R840 and further require that the fluorochromes be conjugated to the respective antibodies in order. The same deficiency applies because the fluorochromes are identified by their commercial designations without independently defining the corresponding fluorochrome compositions or characteristics. Consequently, the scope of the claimed reagent kits is dependent upon the identities of products associated with the recited commercial designations rather than upon definite technical characteristics established by the claim language. Appropriate correction is required.
Regarding claim 2, the claim recites assigning the dim fluorochromes to the relatively higher expressing cell markers and assigning the relatively lower expressing cell markers to bright fluorochromes. The claim further recites avoiding placing the relatively higher expressing cell markers adjacent to co-expressed the relatively lower expressing cell markers for fluorochromes with a same primary excitation laser or similar emission wavelengths. The limitations relatively higher expressing cell markers and relatively lower expressing cell markers render the scope of claim 2 unclear because the claim does not expressly establish the reference or standard against which the relative expression levels of the cell markers are determined. In particular, it is unclear whether the respective expression levels are determined by comparing the twenty cell markers identified in claim 1, comparing markers co-expressed on the same biological cells, comparing expression levels among different biological cell populations, or applying another comparison standard. The distinction is material because the expression level of a particular cell marker may vary depending upon the biological cell population being analyzed. Consequently, a marker characterized as relatively higher-expressing under one comparison may be characterized as relatively lower-expressing under another comparison. Although independent claim 1 identifies twenty cell markers associated with biological cells of interest in AML, claim 2 does not clearly establish whether the relative expression levels are determined among those twenty markers collectively or within particular biological cell populations. Accordingly, the claim does not clearly identify the basis for determining which cell markers must be assigned dim fluorochromes and which must be assigned bright fluorochromes.
Furthermore, claim 2 recites avoiding placing the relatively higher expressing cell markers adjacent to co-expressed the relatively lower expressing cell markers for fluorochromes with a same primary excitation laser or similar emission wavelengths. The expression adjacent to co-expressed the relatively lower expressing cell markers is grammatically unclear and fails to establish the particular relationship that must be avoided between the recited cell markers. Specifically, it is unclear whether the claim requires avoiding the assignment of fluorochromes having adjacent emission wavelengths to relatively higher-expressing and relatively lower-expressing markers, avoiding the assignment of fluorochromes sharing the same primary excitation laser to co-expressed markers, or avoiding some other relationship involving the recited markers.
Moreover, the claim does not clearly establish what constitutes adjacent in the context of the claimed fluorochrome assignment. The term could refer to proximity of fluorochrome emission wavelengths or proximity of fluorochrome spectral characteristics. Accordingly, claim 2 fails to particularly point out and distinctly claim the required relationship between the relative expression levels of the cell markers and the assignment of fluorochromes. Therefore, claim 2 is rejected under 35 U.S.C. 112(b). Appropriate correction is required.
Regarding claim 10, the claim recites processing the received data using a computer processor to form the color flow cytometry panel. However, independent claim 1, from which claim 10 depends, expressly recites combining the plurality of fluorochrome-conjugated antibodies to form the twenty (20) color flow cytometry panel. Thus, independent claim 1 requires formation of the twenty-color flow cytometry panel by combining fluorochrome-conjugated antibodies, whereas dependent claim 10 additionally requires processing data obtained from the full-spectrum flow cytometer using a computer processor to form the color flow cytometry panel. The limitation is indefinite because the claim does not clearly establish how processing data received from the flow cytometer forms the color flow cytometry panel that has already been formed by combining fluorochrome-conjugated antibodies.
In particular, it is unclear whether the computer processor is required to generate a computational representation of the panel, modify a previously constructed panel, or process experimental data obtained using the previously formed panel. These alternatives involve materially different operations. Consequently, the claim does not clearly establish the particular method step required by the limitation processing the received data using a computer processor to form the color flow cytometry panel. Furthermore, claim 10 recites staining the biological cells of interest with the twenty (20) fluorochrome conjugated antibodies, analyzing the multicolor sample through the full spectrum flow cytometer, and receiving data from the detectors of the full spectrum flow cytometer before reciting the computer-processing limitation. Accordingly, the claim describes obtaining experimental flow cytometry data using the twenty fluorochrome-conjugated antibodies and subsequently processing that data to form the panel. However, the claim does not clearly distinguish between the physical formation of the fluorochrome-antibody panel and the computational processing of data obtained using that panel.
The specification describes processing data obtained from flow cytometry analysis, including identifying biological cell populations and generating analytical representations ([0102], p. 19). Additionally, the specification describes computer processing operations ([0135]-[0136], p. 26). Although these disclosures provide context for computational analysis of flow cytometry data, they do not resolve the uncertainty in claim 10 concerning whether the computer-processing step forms a physical reagent panel, a computational representation, or another analytical output. Accordingly, the scope of claim 10 is indefinite.
Regarding claims 11 and 12, these claims depend from claim 10 and therefore incorporate the indefinite limitation processing the received data using a computer processor to form the color flow cytometry panel. Claim 11 further recites determining a limit of detection (LOD) and a lower limit of quantification (LLOQ), while claim 12 further recites assessing a detection sensitivity of the color flow cytometry panel. These additional limitations do not clarify how the computer-processing step required by claim 10 forms the color flow cytometry panel. Therefore, claims 10–12 are rejected under 35 U.S.C. 112(b). Appropriate correction is required.
Response to Arguments
Applicant's arguments filed, 07/30/2026, have been fully considered. The response is set forth below.
Rejection Under 35 U.S.C. § 112(b)
Applicant’s arguments with respect to the rejection of claim 2 under 35 U.S.C. § 112(b) have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of the amended claim language. Applicant argues that the previously identified lack of antecedent basis and ambiguity have been resolved by replacing antigen with cell markers and replacing tertiary marker with lower expressing cell markers. The Examiner agrees that these amendments overcome the particular deficiencies identified in the previous Office Action. Accordingly, the previous § 112(b) rejection of claim 2 is withdrawn.
However, amended claim 2 presents additional uncertainties concerning relatively higher expressing cell markers, relatively lower expressing cell markers, and avoiding placing the relatively higher expressing cell markers adjacent to co-expressed the relatively lower expressing cell markers. Specifically, the claim does not establish the comparison standard for determining relative marker expression or clearly identify the relationship between co-expressed markers that must be avoided. Accordingly, claim 2 is newly rejected under § 112(b) for the reasons set forth in the present Office Action.
Rejection Under 35 U.S.C. § 103
Applicant’s arguments with respect to the rejection of claims 1–7 under 35 U.S.C. § 103 have been fully considered and are persuasive. The rejection of pending claims 1, 2, and 5–7 under 35 U.S.C. § 103 has been withdrawn.
Applicant argues that Soh fails to disclose the particular twenty fluorochrome-antibody combinations required by the independent claims and that Cytek A does not remedy this deficiency. Applicant particularly identifies the difference between cFluor V547 conjugated to anti-CD20 in Cytek A and cFluor V547 conjugated to anti-CD4 in amended claim 1. Applicant further contends that the proposed combination requires selecting particular markers, antibody clones, fluorochromes, and their corresponding assignments using impermissible hindsight.
The Examiner acknowledges that Soh discloses a multicolor flow cytometry panel for detecting measurable residual disease in AML and that Jaimes and Cytek A–E provide teachings concerning spectral flow cytometry and fluorochrome-conjugated antibodies. However, the cited references do not expressly disclose the particular twenty fluorochrome-marker assignments now required by amended claim 1. In particular, identifying a fluorochrome as suitable for multicolor flow cytometry does not, without an adequately supported reason for the specific assignment, establish the obviousness of conjugating that fluorochrome to the particular antibody required by the claim.
Although obviousness does not require bodily incorporation of the references or an express disclosure of every claimed combination in a single reference, the previously articulated rejection does not sufficiently establish why a person of ordinary skill in the art would have selected and combined the particular twenty fluorochrome-marker assignments with a reasonable expectation of success. Accordingly, the previous §103 rejection of claims 1, 2, and 5–7 is withdrawn. The rejection of canceled claims 3 and 4 is moot.
Nonstatutory Double Patenting
Applicant’s arguments with respect to the provisional nonstatutory double patenting rejection of claims 1–7 have been fully considered and are persuasive. The rejection of claims 1, 2, and 5–7 has been withdrawn. Applicant states that the present application and copending U.S. Application No. 18/491,742 are commonly owned by Cytek Biosciences, Inc., and that a terminal disclaimer was submitted to overcome the provisional nonstatutory double patenting rejection. The Examiner acknowledges that the terminal disclaimer directed to U.S. Application No. 18/491,742 has been accepted by the Office. Accordingly, the previously asserted provisional nonstatutory double patenting rejection is withdrawn.
Newly Added Claims 9–22
Applicant states that claims 9–22 have been added and contends that the dependent claims should be allowable because independent claims 1, 6, and 7 have been placed in condition for allowance. The Examiner acknowledges the addition of claims 9–22. However, the patentability of these claims must be determined in view of their respective limitations and the requirements of 35 U.S.C. §112. Specifically, claims 9–12 incorporate the commercially designated fluorochromes recited in claim 1 and are subject to the §112(b) rejection discussed above. Claims 10–12 additionally contain the indefinite computer-processing limitation identified in the present Office Action. Claims 13–22 incorporate the numerical maximum emission wavelength limitations of independent claims 6 and 7 and are subject to the §112(a) written description rejection. Claims 17 and 22 are additionally rejected under § 112(b) based on their recitation of commercially designated cFluor products. Accordingly, Applicant’s assertion that the newly added dependent claims are in condition for allowance is not persuasive in view of the outstanding statutory deficiencies.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/E.O./Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 October 15, 2026
