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 .
Information Disclosure Statements
The information disclosure statements (IDS) filed 11/28/2022, 04/10/2024, 07/17/2024, and 11/19/2024 have been considered by the examiner.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application claims benefit of Foreign Application No. CHINA 202010468262.6 filed 05/28/2020. Based on the filing receipt, the effective filing date of this application is May 28, 2020 which is the filing date of Foreign Application No. CHINA 202010468262.6.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Election/Restrictions
Applicant's election with traverse of Group I, claims 1-6, in the reply filed on 12/10/2025 is acknowledged. The traversal is on the grounds that, after claim amendments filed 12/10/2025, the common technical feature of Groups I-III is the multiple staining of cells in suspension, which is not taught by Andree-Anne, et al. (“Hematoxylin and Eosin Counterstaining Protocol for Immunohistochemistry Interpretation and Diagnosis”, published 2019-08-01, cited in IDS filed 07/17/2024). This is not found persuasive because as stated below in the prior art rejections, the common technical feature of Groups I-III is not a special technical feature.
Claims 7-16 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected Groups II and III, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 12/10/2025.
The requirement is still deemed proper and is therefore made FINAL.
Claim Objections
Claim 1 is objected to because of the following informalities:
Line 3 of claim 1 recites, “cell morphological staining that can be used for pathological diagnosis of on a cell sample”. The claim should recite, “cell morphological staining that can be used for pathological diagnosis of
Lines 11-12 of claim 1 recite, “and then preparing cell suspension”. The claim should recite, “and then preparing the cell suspension”.
Lines 17-18 of claim 1 recite, “and then preparing cell suspension”. The claim should recite, “and then preparing the cell suspension”.
Line 23 of claim 1 recites, “and then preparing cell suspension”. The claim should recite, “and then preparing the cell suspension”.
Line 5 of claim 5 recites, “mucus, tear, lymph, amniotic fluid”. The claim should recite, “mucus, tears, lymph fluid, amniotic fluid”.
Appropriate correction is required.
Note: suggested claim additions are underlined and suggested claim subtractions are stricken-through.
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 3-4 and 6 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 3 recites, “wherein the cell morphological staining that can be used for pathological diagnosis is selected from Diff-Quik staining, Papanicolaou staining, Wright-Giemsa staining, and Hematoxylin/Eosin (H&E) staining, or a derivative or modified form thereof”. It is unclear what is meant by “derivative or modified form thereof”. One of ordinary skill in the art would not know what staining methods are encompassed by a “derivative or modified form thereof” of the stated stains. The applicant’s specification does not ameliorate the lack of clarity. Therefore, the metes and bounds of the claim cannot be determined.
Claims 3-4 contain the trademark/trade name Diff-Quik. 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 the cell morphological staining and, accordingly, the identification is indefinite. Therefore, the metes and bounds of the claims cannot be determined.
Claim 6 recites, “wherein the primary antibody and/or primary probe is a combination of multiple antibodies and/or probes”. It is unclear how the primary antibody and/or primary probe can be a combination of multiple antibodies and/or probes. A singular antibody cannot also be a combination of multiple antibodies. The applicant’s specification does not ameliorate this lack of clarity. Therefore, the metes and bounds of the claim cannot be determined. For clarity, claim 1 could be amended to recite, e.g., “adding one or more primary antibodies and/or one or more primary nucleic acid probes”. Then, claim 6 could be amended to recite, “wherein the one or more primary antibodies and/or nucleic acid probes…”
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 1-2 and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Sun (CN 102288471 A, published 2011-12-21) in view of Krenacs, et al. (“Multiple Antigen Immunostaining Procedures”, published 2010).
Sun teaches a multiple staining method for immunohistochemical staining and cell morphological staining comprising:
a) preparing cell suspension of the cell sample in a container;
b) performing immunohistochemical staining and/or nucleic acid chromogenic in situ hybridization staining on cells in the cell suspension in the container, comprising: i) adding a primary antibody that specifically binds to an antigen to the cell suspension to complete specific binding of the primary antibody to the antigen; ii) removing the unbound primary antibody, and then preparing cell suspension again, iii) adding a secondary antibody conjugated with a label to the cell suspension to specifically bind to the primary antibody; iv) removing the unbound secondary antibody conjugated with a label, and then preparing the cell suspension again,
c) performing cell morphological staining that can be used for pathological diagnosis on the cells in the container, and then smearing the multiply stained cells on a pathological slide, as in claim 1 (see, e.g., a multiple staining method for immunohistochemical staining and cell morphological staining – para. [0017]; step a) – para. [0017], step 1; step b), step i) – para. [0017], step 10; step b), step ii) – para. [0017], step 11; step b), step iii) – para. [0017], step 12; step b), step iv) – para. [0017], step 13; step c) – para. [0017], steps 14-15). It is understood that removing the supernatant in steps 2. and 4. of para. [0017] in Sun removes the unbound antibodies from the cell suspension.
Sun teaches the method wherein steps ii) and iv) are carried out by the following steps:
washing the cells
centrifuging the precipitated cells; and
discarding the supernatant,
as in claim 2 (see, e.g., para. [0017], steps 2-4).
Sun fails to teach the secondary antibody is labeled with a chromogenic enzyme and the chromogenic substrate is added for color development before the excess chromogenic substrate is removed, as in claim 1. Sun also fails to teach wherein the primary antibody is a combination of multiple antibodies to stain the cell, as in claim 6. However, in a journal article titled “Multiple Antigen Immunostaining Procedures”, Krenacs rectifies these deficiencies.
Krenacs teaches antigen immunostaining procedures with the incubation of secondary antibodies labeled with chromogenic enzymes followed by the incubation of the substrate is added with shaking for color development before the excess chromogenic substrate is removed, as in claim 1 (see, e.g., p. 10, under “3.2. Simultaneous Antigen Detection”, steps 3-5; and p. 11, under “3.3.5. IAP/Fast Blue”, step 2). Krenacs teaches the primary antibody is a combination of multiple antibodies to stain the cell, as in claim 6 (see, e.g., p. 10, under “3.2. Simultaneous Antigen Detection”: “In this method, the primary antibodies are combined into a single cocktail and applied simultaneously in a single-reaction step”).
Sun and Krenacs are analogous to the field of the claimed invention because they are both in the field of cell staining. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to incorporate the chromogenic enzymes of Krenacs into the method Sun. An artisan would have been motivated to do so because Krenacs discloses, “Two basic strategies have evolved for the detection of multiple antigens in a tissue section. One strategy is to combine immunoenzymatic methods that use different chromogenic substrate reactions (5–7) (see Chapter 24) and/or the silver-enhanced immunogold technique (IGSS) (8–10) (see Chapter 30). The different colored reaction products can easily be studied against the recognizable background structure with a conventional light microscope, particularly when traditional histological stains such as hematoxylin for nuclei or PAS for basement membranes are additionally applied. With careful balancing of the subsequent chromogenic reactions, up to four antigens situated in separate cell populations or within different compartments of the same cell (nucleus, cytoplasm, or cell membrane) can be distinguished” (see, p. 2, para. 2). The use of chromogenic enzymes allows for distinguishing multiple antigens in cells. An artisan would have a reasonable expectation of success based on the given disclosures.
Furthermore, one of ordinary skill in the art before the effective filing date of the application would have found it obvious to incorporate the combination of multiple antibodies of Krenacs into the method Sun. An artisan would have been motivated to do so because Krenacs discloses, “The immunohistological demonstration of multiple antigens in a single tissue section has many applications and is commonly used to elucidate the topographic relationships of antigenically defined cell populations, and to correlate phenotypic information with functional or prognostic markers, or with microbial infection” (see, p. 1, under “1. Introduction”, para. 1). The combination of multiple antibodies allows for demonstrating multiple antigens with the benefits outlined above. An artisan would have a reasonable expectation of success based on the given disclosures.
Claims 3-4 are rejected under 35 U.S.C. 103 as being unpatentable over Sun (cited above) and Krenacs (cited above), as applied to claims 1-2 and 6 above, and further in view of Liu (US 20150204728 A1, published 2015-07-23).
Sun and Krenacs teach as set forth above, but fail to teach the cell morphological staining is Diff-Quik staining. However, in a U.S. patent application publication, Liu rectifies this deficiency. Liu teaches morphological staining of cells with Diff-Quik staining, as in claims 3-4 (see, e.g., para. [0155]).
Sun, Krenacs, and Liu are analogous to the field of the claimed invention because they are all in the field of cell staining. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to use the Diff-Quik of Liu in the method of Sun and Krenacs. An artisan would have been motivated to do so because Liu teaches “The Diff-Quik method was chosen since it is the simplest and quickest cytology preparation, most commonly used for on-site cytological diagnosis” (see, para. [0157]). An artisan would have had a reasonable expectation of success based on the given disclosures.
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Sun (cited above) and Krenacs (cited above), as applied to claims 1-2 and 6 above, and further in view of Mendoza, et al. (“Fine Needle Aspiration Cytology of the Breast: The Nonmalignant Categories”, published 2011-05-19).
Sun and Krenacs teach as set forth above, but fail to teach the cell sample is a fine needle aspiration sample, as in claim 5. However, in a journal article on fine needle aspiration cytology of the breast, Mendoza rectifies this deficiency. Mendoza teaches the use of fine needle aspiration cytology as tool for assessing cells, as in claim 5 (see, e.g., p. 1, under abstract: “Fine needle aspiration cytology (FNAC) is widely adopted for the pathologic assessment because of its accuracy and ease of use”).
Sun, Krenacs, and Mendoza are analogous to the field of the claimed invention because they are all in the field of cytology. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to use the fine needle aspiration cytology of Mendoza in the method of Sun and Krenacs. An artisan would have been motivated to do so because Mendoza teaches “Fine needle aspiration cytology (FNAC) has become popular as a valuable tool in preoperative assessment of breast masses, and it shows high accuracy, sensitivity, and specificity. It has gained popularity due to its fast and easy approach, being inexpensive, and can be performed with little complications” (see, p. 1, under “1. Introduction”, para. 1). An artisan would have had a reasonable expectation of success based on the given disclosures.
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 1-5 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 60 of copending Application No. 17/999,542 (referred to as ‘542 hereto) in view of Sun (cited above).
‘542 teaches a multiple staining method comprising: preparing cell suspension of the cell sample in a container, performing immunocytochemistry and/or chromogenic in-situ hybridization staining, and performing morphological staining of the cells, as in claim 1 (see, claim 1 of ‘542). ‘542 teaches the morphological staining is Diff-Quik staining, as in claims 3-4 (see, claim 60 of ‘542). ‘542 teaches the sample is urinary exfoliated cells form the patient, as in claim 5 (see, claim 1 of ‘542).
‘542 fails to teach the removing the unbound antibodies, as in claim 1. ‘542 fails to teach washing the cells, centrifuging the cells, and discarding the supernatant, as in claim 2.
However, in a Chinese patent document, Sun (cited above) rectifies these deficiencies. Sun teaches the method of removing unbound antibodies wherein steps ii) and iv) are carried out by the following steps:
washing the cells
centrifuging the precipitated cells; and
discarding the supernatant,
as in claim 2 (see, e.g., para. [0017], steps 2-4).
‘532 and Sun are analogous to the field of the claimed invention because they are both in the field of cell staining. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to use the washing steps of Sun in the method of ‘532. An artisan would have been motivated to do so because Sun teaches the method has a “good dyeing result” (see, para. [0008]). An artisan would have had a reasonable expectation of success based on the given disclosures.
This is a provisional nonstatutory double patenting rejection.
Claim 6 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 60 of copending Application No. 17/999,542 (referred to as ‘542 hereto) and Sun (cited above), as applied to claims 1-5 above, and further in view of Krenacs (cited above).
‘532 and Sun teach as set forth above. But, ‘532 and Sun fail to teach the primary antibody is a combination of multiple antibodies, which stain cell membrane, as in claim 6. However, in a journal article titled “Multiple Antigen Immunostaining Procedures”, Krenacs rectifies this deficiency.
Krenacs teaches the primary antibody is a combination of multiple antibodies to stain the cell, as in claim 6 (see, e.g., p. 10, under “3.2. Simultaneous Antigen Detection”: “In this method, the primary antibodies are combined into a single cocktail and applied simultaneously in a single-reaction step”).
‘532, Sun, and Krenacs are analogous to the field of the claimed invention because they are all in the field of cell staining. One of ordinary skill in the art before the effective filing date of the application would have found it obvious to incorporate the combination of multiple antibodies of Krenacs into the method Sun. An artisan would have been motivated to do so because Krenacs discloses, “The immunohistological demonstration of multiple antigens in a single tissue section has many applications and is commonly used to elucidate the topographic relationships of antigenically defined cell populations, and to correlate phenotypic information with functional or prognostic markers, or with microbial infection” (see, p. 1, under “1. Introduction”, para. 1). The combination of multiple antibodies allows for demonstrating multiple antigens with the benefits outlined above. An artisan would have a reasonable expectation of success based on the given disclosures.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
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/MICHAEL CAMERON SVEIVEN/ Examiner, Art Unit 1678
/GREGORY S EMCH/ Supervisory Patent Examiner, Art Unit 1678