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
This application is a 371 of PCT/EP2022/060498, filed 4/21/2022. This application claims benefit to foreign application PCTIB2021000307, filed 4/21/2021. Claims 1-7 and 17-18 are pending and have been examined on the merits.
Information Disclosure Statement
The information disclosure statement submitted on 10/20/2023 has been considered by the examiner.
Drawings
The drawings are objected to for the following reason:
37 CFR 1.84 (u)(1) states "View numbers must be preceded by the abbreviation "FIG."" In the instant application, the view numbers for Figures 1-5 are preceded by the word "Figure" instead of the abbreviation "FIG.". Additionally, some of the figures and view labels, i.e., A-F, are followed by numbers in parentheses which are not the sheet numbers. These numbers should be removed because they are unnecessary and may be confused for the sheet numbers. The sheet numbers are correctly formatted and placed; hence, they do not need to be modified, just the numbers following “Figure 4”, Figure 5”, “B” and “C”. Views which are distributed over multiple sheets should be given their own designation rather than the numbers in parentheses mentioned above. In other words, Fig. 5B (1/3) should be Fig. 5B, Fig. 5B (2/3) should be Fig. 5C, Fig. 5B (3/3) should be Fig. 5D, Fig. 5C (1/2) should be Fig. 5E and Fig. 5C (2/2) should be Fig. 5F, Fig. 5D should be Fig. 5G, Fig. 5E should be Fig. 5H and Fig. 5F should be Fig. 5H.
The specification should be amended to match the amended figures.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 4-5 and 17-18 are objected to because of the following informalities:
Claim 4 recites “wherein expression CD19+ CD27- CD21- CD11c++ CXCR5+ Tbet++ CD95+ FCRL3+ for the markers for which the level cellular expression has been determined” which should be “wherein expression of CD19[[+]]+, CD27[[-]]-, CD21[[-]]-, CD11c[[++]]++, CXCR5[[+]]+, Tbet[[++]]++, CD95[[+]]+ or FCRL3[[+]]+ for the markers for which the level cellular expression has been determined” because intensity level of cellular markers is usually indicated with superscripted indicators, alternatives should be separated with a comma and for grammar.
Claim 5 recites “expression CD19+ CD27- CD21- CD11c++ CXCR5+ Tbet++ CD95+ FCRL3+ in B cells from the biological sample, for the markers for which the level cellular expression has been determined” which should be “expression[[ ]] CD19[[+]]+, CD27[[-]]-, CD21[[-]]-, CD11c[[++]]++, CXCR5[[+]]+, Tbet[[++]]++, CD95[[+]]+ or FCRL3[[+]]+ in B cells from the biological sample, for the markers for which the level cellular expression has been determined” because intensity level of cellular markers is usually indicated with superscripted indicators, alternatives should be separated with a comma and for grammar.
Claim 17 recites “that express the marker proteins selected amongst: CD3+ CD4+ TNFα+ CXCR3- CCR6- IL-21- CXCR5- IL-17- IL-4- IFNƔ+ or - in T cells” which should be “that express the marker proteins selected amongst: CD3[[+]]+, CD4[[+]]+, TNFα[[+]]+, CXCR3[[-]]-, CCR6[[-]]-, IL-21[[-]]-, CXCR5[[-]]-, IL-17[[-]]-, IL-4[[-]]- or IFNƔ[[+]]+/- in T cells” because intensity level of cellular markers is usually indicated with superscripted indicators, alternatives should be separated with a comma and for grammar.
Claim 18 recites “the expression level of one of the marker proteins: CD3 CD4 TNFα CXCR3 CCR6 IL-21 CXCR5 IL-17 IL-4 IFNƔ in T cells” which should be “the expression level of one of the marker proteins: CD3, CD4, TNFα, CXCR3, CCR6, IL-21, CXCR5, IL-17, IL-4 or IFNƔ in T cells” because alternatives should be separated with a comma and for grammar.
Appropriate correction is required.
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 1-7 and 17-18 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.
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 1 recites the broad recitation “detecting the presence of pathogenic B cells in the test sample, that express the marker proteins CD19, CD27, CD21, CD11c, CXCR5”, and the claim also recites “optionally at least one marker protein selected in the group consisting of Tbet, CD95, FCRL3, FCRL5, IgM, IgD, CD24, CD38 and/or G6” which is the narrower statement of the range/limitation.
Claim 3 recites the broad recitation “detecting CD19, CD27, CD21, CD11c, and CXCR5”, and the claim also recites “optionally at least one marker protein selected from the group consisting of: Tbet, CD95, FCRL3, FCRL5, IgM, IgD, CD24, CD38 and G6” which is the narrower statement of the range/limitation.
Claim 4 recites the broad recitation “determining the level of cellular expression of CD19, CD27, CD21, CD11c, CXCR5”, and the claim also recites “optionally at least one marker protein selected in the group consisting of Tbet, CD95 and/or FCRL3” which is the narrower statement of the range/limitation.
Claim 5 recites the broad recitation “determining the level of cellular expression of CD19, CD27, CD21, CD11c, CXCR5”, and the claim also recites “optionally at least one marker protein selected in the group consisting of Tbet, CD95 and/or FCRL3” which is the narrower statement of the range/limitation.
Claim 6 recites the broad recitation “reagents, each being used to determine the expression level of one of the marker proteins CD19, CD27, CD21, CD11c, CXCR5”, and the claim also recites “optionally Tbet, CD95, FCRL3, FCRL5, IgM, IgD, CD24, CD38 and/or G6” which is the narrower statement of the range/limitation.
Claim 7 recites the broad recitation “determining the expression of marker proteins CD19, CD27, CD21, CD11c, CXCR5”, and the claim also recites “optionally at least one marker protein selected in the group consisting of Tbet, CD95, FCRL3, FCRL5, IgM, IgD, CD24, CD38 and/or G6” which is the narrower statement of the range/limitation.
The claims are 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.
Claims 2 and 17 depend from claim 1 and do not resolve the indefiniteness; hence, claims 2 and 17 are rejected under 35 U.S.C. 112(b) as being indefinite.
Claims 18 depends from claim 7 and do not resolve the indefiniteness; hence, claim 18 is rejected under 35 U.S.C. 112(b) as being indefinite.
The term “about” in claim 2 is a relative term which renders the claim indefinite. The term “about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Hence, the metes and bounds of the variation from healthy donors for each of the marker proteins is indefinite; therefore, claim 2 is rejected under 35 U.S.C. 112(b) as being indefinite.
The abbreviations “pSS” and “L-pSS” in claim 1 renders the claim indefinite. The abbreviations “pSS” and “L-pSS” should be spelled out upon their first occurrence. Claims 2-7 and 17-18 depend from claim 1 and do not resolve the indefiniteness; hence, claims 1-7 and 17-18 are rejected under 35 U.S.C. 112(b) as being indefinite.
Claim 1 recites the limitation "the autoimmune disease" in line 9. There is insufficient antecedent basis for this limitation in the claim because the claim does not previously recite an autoimmune disease. Claims 2-7 and 17-18 depend from claim 1 and do not resolve the indefiniteness; hence, claims 1-7 and 17-18 are rejected under 35 U.S.C. 112(b) as being indefinite.
Claim 1 recites the limitation “A method of diagnosing of pSS, L-pSS and lymphoma in a subject” which appears to be limiting the method to diagnosing subjects with pSS, L-pSS AND lymphoma. It would appear that the limitation should be “A method of diagnosing[[ of]] pSS, L-pSS or lymphoma in a subject”; hence, the wording of the claim is indefinite. Claims 2-7 and 17-18 depend from claim 1 and do not resolve the indefiniteness; hence, claims 1-7 and 17-18 are rejected under 35 U.S.C. 112(b) as being indefinite.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 18 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 18 recites the kit according to claim 7; however, claim 7 does not recite a kit; hence, claim 18 fails to include all the limitations of the claim upon which it depends.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-2, 7 and 17 are rejected under 35 U.S.C. 101 because the claimed invention is directed to judicial exception without significantly more.
Claims 1-2, 7 and 17 are drawn to methods comprising a mental step, i.e., a judicial exception.
The first question in the subject matter eligibility determination is “Is the claim to a process, machine, manufacture or composition of matter?” (Step 1)
Yes, claims 1-2, 7 and 17 are drawn to methods, i.e., a process.
The second question (Step 2A, prong 1) in the subject matter eligibility determination asks “Is the claim directed to a law of nature, a natural phenomenon, or an abstract idea (judicially recognized exceptions)?"
Yes, the claimed processes are drawn to processes comprising an abstract idea (mental step; judicial exception) and well understood, conventional and routine laboratory steps.
Regarding claims 1-2 and 17, the processes are drawn to obtaining a test sample from the subject and detecting the presence of pathogenic B cells in the test sample, that express the marker proteins CD19, CD27, CD21, CD11c, CXCR5, and optionally at least one marker protein selected in the group consisting of Tbet, CD95, FCRL3, FCRL5, IgM, IgD, CD24, CD38 and/or G6 at a different level compared to a baseline level established from a healthy donor sample and wherein the presence of said pathogenic B cells in the sample, identifies the subject as having or likely to develop the autoimmune disease or a lymphoproliferative form or a chronic inflammatory form of an autoimmune disease, i.e., a mental step, which is an abstract idea or intangible relationship, which is a judicial exception.
Regarding claim 7, the process is drawn to determining the expression of marker proteins CD19, CD27, CD21, CD11c, CXCR5, and optionally at least one marker protein selected in the group consisting of Tbet, CD95, FCRL3, FCRL5, IgM, IgD, CD24, CD38 and/or G6 in B cells in a sample taken from the subject before administering the treatment; detecting the presence of pathogenic B cells in a sample taken from the subject after administering the treatment; and comparing the level of expression of said marker proteins in the sample taken from the subject before administering the treatment to the level expression of said marker proteins in the sample taken from the subject after administering the treatment, i.e., a mental step, which is an abstract idea or intangible relationship, which is a judicial exception.
Step 2A, prong 2 asks “Does the claim recite additional elements that integrate the judicial exception into a practical application?”
Regarding claims 1-2, 7 and 17, no, the claims do not integrate the judicial exception into a practical application because the claims do not recite any practical steps to be taken upon making the mental step of diagnosing the subject as having or likely to develop an autoimmune disease or a lymphoproliferative form or a chronic inflammatory form of an autoimmune disease (claims 1-2 and 17) or comparing the level of expression of said marker proteins before and after treatment (claim 7).
The final question (Step 2B) in the subject matter eligibility determination to be asked is “Does the claim recite additional elements that amount to significantly more than the judicial exception?”
No, claims 1-2, 7 and 17 do not recite additional elements that amount to significantly more than the judicial exception.
Regarding claims 1-2, 7 and 17, determining the expression of marker proteins in B cells in a sample taken from the subject is well-understood, routine and conventional as evidenced by Saadoun et al., 2013 (cite U, attached PTO-892; herein “Saadoun”; Abst.; pp. 1086-1087, “MATERIALS AND METHODS”).
These well-understood, routine, conventional activities are not part of a specific transformative method, but rather represent generalized method steps which are executed solely for the production of data for the mental step. Accordingly, claims 1-2, 7 and 17 do not amount to significantly more than the judicial exceptions and are not patent eligible.
Thus, claims 1-2, 7 and 17 are rejected under U.S.C. 101 as not being drawn to patent eligible subject matter.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 1, 3-7 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Sachinidis et al., 2020 (cite U, attached PTO-892; herein “Sachinidis”).
Sachinidis teaches methods of prognosis, diagnosis and therapy of systemic lupus erythematosus (SLE) (Title) in a patient wherein the diagnosis comprises characterizing cell populations, from the patients, comprising B cell subsets with a phenotype of CD19+, CD21-, CD11c+ and T-bet+, i.e., age-associated B cells (ABCs), or B cell subsets with a phenotype of CD19+, IgD-, CD27-, CXCR5- and T-bet+, i.e., double negative 2 cells, i.e., DN2 cells (Abst.); wherein the B cells of the patient are isolated from peripheral blood mononuclear cells (PBMCs; Table 3). Sachinidis teaches that these ABC cells are produced in Sjögren’s syndrome (p. 312, “AGE-ASSOCIATED B CELLS (ABCs): MAIN FEATURES AND FUNCTIONS”), i.e., pSS, and that the ABCs expand dramatically in autoimmunity (Abst.). Sachinidis teaches that ABC and DN2 subsets are expanded in patients with SLE (p. 314, “Data derived from humans”), that prevention of ABC formation may have a therapeutic effect on patients with SLE (p. 314, “Regulation of ABCs in systemic autoimmunity”) and that ABCs are expanded in patients with SLE as compared to healthy individuals, and the expansion correlates with the severity of clinical manifestations as determined by the disease activity index SLEDAI (pp. 314-315, “ABCs IN THE PATHOPHYSIOLOGY OF HUMAN AUTOIMMUNITY: EMPHASIS ON SLE”). Sachinidis teaches that the ABCs are associated with autoimmunity, stating that “ABC” has also been interpreted as “autoimmune-associated B cells” (p. 315, “IS “AGE-ASSOCIATED B CELLS” A PROPER DESIGNATION AFTER ALL?”). Sachinidis teaches that correlating the cell populations with the clinical profile of the patients should allow better patient stratification and monitoring (Abst.).
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice a method of diagnosing pSS in a subject comprising obtaining a test sample from the subject and detecting the presence of pathogenic B cells in the test sample by detecting CD19, CD27, CD21, CD11c, CXCR5, Tbet and IgD at a different level compared to a baseline level established from a healthy donor sample and wherein the presence of said pathogenic B cells in the sample identifies the subject as having or likely to develop pSS because Sachinidis teaches the detection of pathogenic B cells (ABCs and DN2s) as diagnostic for autoimmune disease, which can be Sjögren’s syndrome (ABCs are elevated in Sjögren’s syndrome), i.e., pSS, by detecting CD19, CD27, CD21, CD11c, CXCR5, Tbet and IgD in the cells; therefore, claims 1 and 3-5 are prima facie obvious.
Regarding claim 7, Sachinidis teaches using the method for patient stratification and monitoring (Abst.); hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Sachinidis to evaluate the efficacy of a treatment of an autoimmune disease or a lymphoproliferative form or a chronic inflammatory form of an autoimmune disease in a subject, comprising determining the expression of marker proteins CD19, CD27, CD21, CD11c, CXCR5, Tbet and IgD in B cells in a sample taken from the subject before administering the treatment; detecting the presence of pathogenic B cells in a sample taken from the subject after administering the treatment; and comparing the level of expression of said marker proteins in the sample taken from the subject before administering the treatment to the level expression of said marker proteins in the sample taken from the subject after administering the treatment because Sachinidis teaches using the method for patient stratification and monitoring; therefore, claim 7 is prima facie obvious.
Regarding claims 6 and 18, a person of ordinary skill in the art at the time of filing would have found it obvious to assemble the reagents for practicing the method made obvious by Sachinidis because kits are a convenient way to commercialize practicing a method. Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to produce a kit comprising reagents, each being used to determine the expression level of one of the marker proteins CD19, CD27, CD21, CD11c, CXCR5, Tbet and IgD in order to commercialize the practice of the method made obvious by Sachinidis; therefore, claims 6 and 18 are prima facie obvious.
NOTE: Intended use recitations in composition claims (kit claims are composition claims) are met if the composition COULD be used for the intended use. Whether the prior art teaches the intended use or not is irrelevant if the prior art or combination of prior art discloses or makes obvious the claimed composition. Hence, the limitations “for the diagnosis of pSS, L-pSS and lymphoma in a subject or for the detection of pathogenic B cells” and “used to determine the expression level of one of the marker proteins” in claim 6 and “each being used to determine the expression level of one of the marker proteins” and “in T cells; in a sample” are intended use recitations which are met by compositions which COULD be used for these intended use recitations.
Claims 1, 3-7 and 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Sachinidis in view of Renand et al., US 2022/0317120 (cite A, attached PTO-892; herein “Renand”).
The discussion of Sachinidis regarding claims 1, 3-7 and 18 set forth in the rejection above is incorporated herein.
Sachinidis is silent on detecting the presence of pathogenic T cells in the patient’s sample; however, a person of ordinary skill in the art at the time of filing would have found it obvious to detect the presence of pathogenic T cells in the patient’s sample in view of the disclosure of Renand.
Renand teaches diagnosing the active autoimmune pathology in a subject by detecting pathogenic T cells which are CD3+ (Abst.; Fig. 1).
Hence, a person of ordinary skill in the art at the time of filing would have found it obvious to practice the method made obvious by Sachinidis further comprising detecting pathogenic T cells in the test sample from the subject comprising detecting that the pathogenic T cells are CD3+ because Renand teaches diagnosing the active autoimmune pathology in a subject by detecting pathogenic T cells which are CD3+; therefore, claim 17 is prima facie obvious.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Trent R Clarke whose telephone number is (571)272-2904. The examiner can normally be reached M-F 10-7 MST.
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/TRENT R CLARKE/ Examiner, Art Unit 1651
/DAVID W BERKE-SCHLESSEL/ Primary Examiner, Art Unit 1651