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 .
DETAILED ACTION
Election/Restrictions
1. Applicant's election of Group I, claims 1, 30-32, 33(a), 33(c), 33(d), 34, 36-41, 46(a), 46(c), 46(d), 47-52, 55, and 56, filed July 8, 2026 is acknowledged and has been entered. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Claims 33(b), 33(e), 33(f), 33(g), 35, 42-45, 46(b), 46(e), 46(f), 46(g), 53, and 54 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being claims drawn to a non-elected invention. Accordingly, claims 1 and 30-56 are pending. Claims 1, 30-32, 33(a), 33(c), 33(d), 34, 36-41, 46(a), 46(c), 46(d), 47-52, 55, and 56 are under examination.
Priority
2. 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 is a divisional of United States application serial number (ASN) 17/031,732 filed 09/24/2020, now U.S. Patent 12,038,437; which is a divisional of ASN 15/523,309 filed 04/28/2017, now U.S. Patent 10,802,023; which is a 371 National Stage application of PCT/NL2015/050762 filed 10/30/2015; and which claims the benefit of Provisional Application Number 62/072,498 filed 10/30/2014. Based on the filing receipt, the effective filing date of this application is October 30, 2014 which is the filing date of Provisional Application Number 62/072,498 from which the benefit of priority is claimed.
Specification
3. A reference to the prior application ASN 17/031,732 filed 09/24/2020 has been inserted in the first sentence of the specification of this application or in an application data sheet (37 CFR 1.76), under 35 U.S.C. 119(e), 120, 121, or 365(c). See 37 CFR 1.78(a). However, the current status of parent ASN 17/031,732, i.e. US Patent Number, pending, abandoned, is missing.
Claim Objections
4. Claim 31 is objected to for depending from a cancelled claim. Appropriate correction is required.
Information Disclosure Statement
5. The listing of references in the specification in pages 26-28 is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
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.
6. Claims 1, 30-34, 36-41, 46-52, 55, and 56 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 pre-AIA the applicant regards as the invention.
Claim 1 is vague and indefinite in reciting, “A reagent composition for flow cytometric immunophenotyping of leukocytes” in the preamble and “comprising a panel of fluorochrome-conjugated antibodies directed against … combination of markers” because it is unclear how the leukocytes can be immunophenotyped using a same fluorochrome which is encompassed in the claimed invention. Perhaps, Applicant intends “comprising a panel of fluorochrome-conjugated antibodies directed against … combination of markers, wherein the fluorochromes conjugated to each of the antibodies in the panel are distinguishably distinct.” See also claims 31, 33 (i), 33 (ii)(a), 34, 46(i), 46(ii)(a), 47(i), 47(ii), 48(ii), 49(i), 49(ii), 50(i), 50(ii), 51(i), 51(ii), 52(ii), 55(i), 56(i), and 56(iii).
Claim 32, line 8 lacks clear antecedent basis in reciting “IgG4.”
Claim 33 in part (ii) is vague and indefinite in reciting, “(ii) a second reagent composition comprising a panel of fluorochrome-conjugated antibodies directed against one of … combinations of markers: (a)” because it is unclear how the leukocytes can be immunophenotyped as set forth in claim 1 from which the instant claim depends using a fluorochrome which is encompassed in the claimed invention. Perhaps, Applicant intends “comprising a panel of fluorochrome-conjugated antibodies directed against … combination of markers, wherein the fluorochromes conjugated to each of the antibodies in the panel are distinguishably distinct.”
Claim 40 is indefinite in reciting “A diagnostic kit … comprising a reagent composition according to claim 1, optionally together with instructions for use, buffer, and/or control samples” because it is unclear how the “reagent composition” in claim 1 is different from the “diagnostic kit’ recited in the instant claim, absent the “instructions for use, buffer, and/or control samples” in the diagnostic kit which is encompassed in the claimed invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 41 recites the broad recitation “for the identification of alteration in leukocyte subsets in an immunological disease,” and the claim also recites “preferably for immune monitoring of a patient having infection, autoimmune disease, allergy, after transplantation, vaccination….” which is the narrower statement of the range/limitation. The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Regarding claim 41, the phrase "other type of immune therapy" renders the claim indefinite because the claim includes elements not actually disclosed (those encompassed by "other type"), thereby rendering the scope of the claim unascertainable. See MPEP § 2173.05(d).
Claim 48 in part (ii) is vague and indefinite in reciting, “a second reagent composition comprising a panel of fluorochrome-conjugated antibodies directed against … combination of markers” because it is unclear how the leukocytes can be immunophenotyped as set forth in claim 1 from which the instant claim ultimately depends using a fluorochrome which is encompassed in the claimed invention. Perhaps, Applicant intends “comprising a panel of fluorochrome-conjugated antibodies directed against … combination of markers, wherein the fluorochromes conjugated to each of the antibodies in the panel are distinguishably distinct.”
Claim 50 in part (ii) is vague and indefinite in reciting, “a second reagent composition comprising a panel of fluorochrome-conjugated antibodies directed against … combination of markers” because it is unclear how the leukocytes can be immunophenotyped as set forth in claim 1 from which the instant claim ultimately depends using a fluorochrome which is encompassed in the claimed invention. Perhaps, Applicant intends “comprising a panel of fluorochrome-conjugated antibodies directed against … combination of markers, wherein the fluorochromes conjugated to each of the antibodies in the panel are distinguishably distinct.”
Claim 52 in part (ii) is vague and indefinite in reciting, “a second reagent composition comprising a panel of fluorochrome-conjugated antibodies directed against … combination of markers” because it is unclear how the leukocytes can be immunophenotyped as set forth in claim 1 from which the instant claim ultimately depends using a fluorochrome which is encompassed in the claimed invention. Perhaps, Applicant intends “comprising a panel of fluorochrome-conjugated antibodies directed against … combination of markers, wherein the fluorochromes conjugated to each of the antibodies in the panel are distinguishably distinct.”
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.
7. Claims 1, 31-34, 36-41, 46, 47, 49, 51, 55, and 56 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 10,802,023. Although the claims at issue are not identical, they are not patentably distinct from each other because both inventions recite a reagent composition and kit for the flow cytometric immunophenotyping of leukocytes involved in primary immunodeficiencies of the lymphoid system (lymphocyte subpopulations: B cells) comprising a panel of fluorochrome-conjugated antibodies directed against a combination of markers: CD19, CD21, CD27, CD38, IgM, IgD, and IgG including IgG1, IgG2, and IgG3; wherein the combination of markers further comprises CD5, CD24, IgG4, and IgA including IgA1 and IgA2. Both inventions further recite a second reagent composition and kit comprising a second reagent composition comprising a panel of fluorochrome-conjugated antibodies directed against a combination of markers: a) CD19, CD21, CD27, CD38, CD5, CD24, IgM, and IgD; or c) CD19, CD21, CD27, CD38, IgM, IgD, IgG1, IgG2, and IgG3; or d) CD19, CD21, CD27, CD38, IgM, IgD, IgA1, IgA2, and IgG4. Both inventions further recite a third reagent composition and kit comprising a third reagent composition comprising a panel of fluorochrome-conjugated antibodies directed against a combination of markers: CD27, CD45RA, CD45, CD16, CD3, CD8, IgD, CD4, IgM, CD56, CD19, CCR7 (CD197), CD38, either CD31 or HLA-DR, and either TRCαβ or TCRγδ, wherein the fluorochromes are distinguishably distinct; and wherein each antibody directed against the markers within each of the pairs CD8/IgD, CD4/IgM and CD19/ TRCαβ or CD19/ TCRγδ is conjugated to the same fluorochrome.
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.
8. Claims 1, 33, 39-41, 46, and 51 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kamphuis et al. (Perigranuloma Localization and Abnormal Maturation of B Cells. Am J Respir Crit Care Med 187 (4): 406-416 (February 15, 2013)- IDS).
Kamphuis et al. teach a reagent composition for the flow cytometric immunophenotyping of leukocytes involved in primary immunodeficiencies (abnormal immunoglobulin responses) of the lymphoid system (B cell subsets) comprising a panel of fluorochrome-conjugated antibodies directed against a combination of markers: CD19, CD21, CD27, CD38, IgM, IgG, IgA, IgD, and also CD24 (Abstract; p. 407, col. 2, 1st full ¶; Figure 2). The fluorochromes of the fluorochrome-conjugated antibodies are detectably distinct and comprise fluorescein isothiocyanate (FITC), phycoerythrin (PE), peridinin chlorophyl protein/cyanine 5.5 (PerCP-Cy5.5), phycoerythrin/cyanine 7 (PE-Cy7), allophycocyanine (APC), allophycocyanine/hilite 7 (APC-H7), pacific blue (PB), and pacific orange (PO) (p. 407, col. 2, 1st full ¶; p. 408, col. 2, 3rd full ¶ to p. 409; Figure 2). Kamphuis et al. also teach second and third reagent compositions comprising panel combinations of fluorochrome-conjugated antibodies directed against CD19, CD21, CD27, CD38, IgM, IgD, IgG1, IgG2, and IgG3; wherein the reagent composition comprises two distinctly labeled antibodies against IgG2 and wherein each antibody directed against the markers within each of the pairs IgG3/IgG2 and IgG1/IgG2 is conjugated to the same fluorochrome (p. 407, col. 2, 1st full ¶; p. 409-411; Table 2; Figure 2, Figure 5C). The second and third reagent compositions may also comprise panel combinations of fluorochrome-conjugated antibodies directed against CD19, CD21, CD27, CD38, IgM, IgD, IgG4, IgA1, and IgA2; wherein the reagent composition comprises two distinctly labeled antibodies against IgA1 and wherein each antibody directed against the markers within each of the pairs IgA1/IgG4 and IgA1/IgA2 is conjugated to the same fluorochrome (p. 407, col. 2, 1st full ¶; p. 409-411; Table 2; Figure 2, Figure 5C). The reagent compositions as taught by Kamphuis et al. are shown in page 407, column 2 to be incorporated into kit formats including control samples (Figure 2; Table 2; Figure 5C). Kamphuis et al. teach using reagent compositions for the identification of alterations in leukocyte subsets in subjects (patients) having an immunological disease including infection (influenza virus), autoimmune disease (Sarcoidosis: inflammatory disease), or vaccination and immune antibody therapy (Abstract; Table 1; Figure 2).
Accordingly, Kamphuis et al. appears to read on Applicant’s claimed invention.
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.
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.
9. Claims 30-32, 34, 36-38, 47-50, 52, and 55 are rejected under 35 U.S.C. 103 as being unpatentable over Kamphuis et al. (Am J Respir Crit Care Med 187 (4): 406-416 (February 15, 2013)) in view of Locke et al. (Laboratory Diagnosis of Primary Immunodeficiencies. Clinic Rev Allerg Immunol 46: 154-468 (February 26, 2014) - IDS).
Kamphuis et al. is discussed supra. Kamphuis et al. is silent in teaching CD5 and IgE as primary immunodeficiency markers of the lymphoid system.
Locke et al. teach that primary immune deficiencies represent highly heterogeneous group of disorders with an increased propensity to infections and other immune complications including allergy and indicated the significance of using flow cytomeric-based assays in measuring immune cell function (Abstract). For humoral immunodeficiency, Locke et al. teach use of a reagent composition for quantitative evaluation of immunoglobulin markers including IgM, IgG, IgA, and IgE (p. 155, col. 1, 1st full ¶; p. 162, col. 1, last ¶; Table 1). For chronic variable immunodeficiency, Locke et al. teach quantitative evaluation of B lymphocyte markers including CD19 (B cell marker), CD27, CD38, IgM, IgD, IgA, CD4, CD8, CD45RA (p. 155, col. 1, last ¶ to p. 156; Figure 1). For autoimmune Lymphoproliferative Syndrome, Locke et al. teach quantitative evaluation of B lymphocyte markers including CD19, CD27, CD3, CD4, CD8, CD5, HLADR, and TRCαβ (p. 165; Figure 8).
It would have been obvious to one of ordinary skill in the art at the time the invention was filed to further incorporate fluorochrome-conjugated antibodies directed against CD5 and IgE as taught by Locke into the reagent compositions of Kamphuis because Locke taught using IgE and CD5 as further relevant markers for flow cytometric immunophenotyping of leukocytes for application in the reagent compositions of Kamphuis. One of ordinary skill in the art at the time the invention was filed would have had reasonable expectation of success in incorporating IgE and CD5 as taught by Locke as additional relevant markers for immunophenotyping leukocytes in the reagent compositions taught by Kamphuis for immunophenotyping leukocytes because both of Kamphuis and Locke teach analogous art in immunophenotyping leukocyte subpopulations of the lymphoid system.
It is proper for purposes of this obviousness rejection to interpret the combined general and specific panel reagent combinations of Locke et al. to encompass the reagent compositions for immunophenotyping leucocytes in the claimed invention because unpatented claims are given the broadest reasonable interpretation consistent with the specification.
10. No claims are allowed.
Remarks
11. Prior art made of record are not relied upon but considered pertinent to the applicants' disclosure:
Warnatz et al. (Immune phenotyping in primary immunodeficiency. IPID Protocols (2010)-IDS) in view of O’Gorman et al. (Flow Cytometry Assays in Primary Immunodeficiency Disease. Methods in Molecular Biology 699: 317-335 (2011) - IDS) teach a reagent composition for the flow cytometric immunophenotyping of B cells or B lymphocytes comprising fluorochrome-conjugated antibodies directed against the following combination of markers: CD19, CD21, CD27, CD38, IgM, IgD, IgG (IgG1, IgG2, IgG3, IgG4), and IgA (IgA1, IgA2) (pp. 1-2). In the antibody table, Warnatz et al. teach antibodies against CD27 and CD38 each conjugated to same fluorochromes: fluorescein isothiocyanate (FITC); antibodies against IgA and IgD conjugated to same fluorochromes: phycoerythrin (PE); and antibodies against CD19, CD21, IgM each conjugated to distinguishably distinct fluorochromes: phycoerythrin/cyanine7 (PC7), PE, and cyanine 5 (CY5), respectively (p. 2).
Warnatz et al. (Severe deficiency of switched memory B cells (CD27+ IgM- IgD-) in subgroups of patients with common variable immunodeficiency: a new approach to classify a heterogeneous disease. BLOOD 96:5 (1544-1551 (March 2002) - IDS) teach a reagent composition for the flow cytometric immunophenotyping and sorting of CD27+ IgM- IgD- naïve and/or memory B cells or lymphocytes (Abstract; p. 1545, right column).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GAILENE R. GABEL whose telephone number is (571)272-0820. The examiner can normally be reached Monday, Tuesday, and Thursday 5:30 AM to 4:00 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Gregory S. Emch can be reached at (571) 272-8149. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/GAILENE GABEL/Primary Examiner, Art Unit 1678
July 23, 2026
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