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
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. Claims 1, 3-4, 6-7, 9-12, 14-15, 17-18, 20-23, and 26 have an effective filing date of 12 AUG 2020.
Election/Restriction
In the response filed on 11/19/2025, Applicant elected without traverse:
Species
sPD-L1 as a species of marker measured in a biological sample
anti-PD-1 antibody as a species of immunotherapy
melanoma as a species of cancer; and
sPD-L1 as a species of one or more immunosuppressive components
Status of Claims
Claims 1, 3-4, 6-7, 9-12, 14-15, 17-18, 20-23, and 26 are currently pending and presented for examination on the merits.
Claims 1, 3-4, 12, 14-15, and 23 are amended.
Claims 6 and 17 are withdrawn from further consideration by examiner under 37 CFR 1.142(b) as being drawn to a non-elected species.
Claims 2, 5, 8, 13, 16, 19, and 24-25 are canceled.
Rejections Withdrawn
The rejections filed under 35 U.S.C. 112(b) are withdrawn in view of Applicant’s amendments to claims.
The rejections filed under 35 U.S.C. 103 are withdrawn in view of Applicant’s amendments to claims.
Rejections Maintained
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 23 and 26 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.
Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term “evADAM10” in claim 23 is used by the claim to mean “extracellular vesicles ADAM10”, but the claim nor specification does not properly define the term. The term is indefinite because the specification does not clearly redefine the term. Clarification is required.
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.
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 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.
Claims 1, 3-4, 7, 9-12, 14-15, 18, 20-23, and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Eliaz et al (WO 2015099826 A1, Previous OA), Dronca et al (Bim and soluble PD-L1 (sPD-L1) as predictive biomarkers of response to anti-PD-1 therapy in patients with melanoma and lung carcinoma, ASCO Annual Meeting, Abstract 11534, J Clin Oncol 35, 2017, IDS 1/23/2024), and further in view of Abstract #4 (Association of soluble PD-L1 (sPD-L1) with decreased survival in metastatic melanoma, Abstract #4, ASCO-SITC Clinical Immuno-oncology Symposium, J Clin Oncol 35, 2017, Previous OA).
In regards to claims 1, 12, and 23, Eliaz et al a method of performing plasmapheresis on a patient [0018]. Eliaz et al further teaches using the plasmapheresis to remove components from the blood that may either mediate or reinforce disease conditions [0018]. Eliaz et al further teaches removing receptors that block the effectiveness of antineoplastic medications or treatments [0018]. Eliaz et al further teaches plasmapheresis is also called therapeutic plasma exchange (TPE) [0007]. Eliaz et al further teaches performing TPE to remove elevated gal-3 because it interferes or suppresses antineoplastic regimens, such as chemotherapeutic treatments [0011 & 0014].
Eliaz et al does not specifically teach markers soluble PD-L1. However, this deficiency is made up in the teachings of Dronca et al and Abstract #4.
Dronca et al teaches the existence of soluble PD-L1 [Background]. Dronca et al further teaches soluble PD-L1 is biologically active and capable of triggering apoptosis in activated T-cells [Background]. Dronca et al further teaches measuring soluble PD-L1 in melanoma patients undergoing anti-PD1 therapy [Background].
Abstract #4 teaches tumor-derived PD-L1 has additional systemic effects through the release of biologically active soluble forms of PD-L1 into the circulation, which further impedes the anti-tumor immune response and contributes to poor clinical outcomes in multiple myeloma patients [Background].
One of ordinary skill in the art, before the effective filing date, would have been motivated to combine Eliaz’s methods of treating patients by performing a TPE on a patient with a marker in a biological sample that is equal to or higher than a threshold level and administering an immunotherapy, with Dronca’s method of soluble PD-L1 being biologically active and triggering apoptosis in activated T-cells in melanoma patients undergoing anti-PD-1 therapy, with Abstract #4 method of observing soluble PD-L1 impeding anti-tumor responses and contributing to poor clinical outcomes. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine Eliaz, Dronca, and Abstract #4’s methods to arrive at a method of performing TPE on a mammal identified as having equal or elevated soluble PD-L1 compared to a threshold level, and administering immunotherapy, because Eliaz teaches removing components using TPE that suppress or interfere with medications, and Dronca teaches that soluble PD-L1 triggers apoptosis in activated T-cells. Furthermore, Abstract #4 teaches soluble PD-L1 impeding anti-tumor responses and contributing to poor clinical outcomes.
In regards to claims 3-4 and 14-15, Dronca et al teaches that a high baseline for sPD-L1 is 2.8 ng/ml and a normal baseline of 0.7 ng/ml [Results]. Furthermore one of ordinary skill in the art would have been motivated, based upon the cited references, to determine a threshold that correlates with resistance to anti-PD-1 therapy.
In regards to claims 7 and 18, Dronca et al teaches measuring sPD-L1 with ELISA [Methods].
In regards to claims 9 and 20, Abstract #4 teaches a method of measuring the level of sPD-L1 with an ELISA in melanoma patients then treating with an anti-PD-1 antibody pembrolizumab [Background, Methods, & Results]. Abstract #4 further teaches samples from blood donations and plasma samples from melanoma patients [Methods]. Abstract #4 further teaches a normal mean value for sPD-L1 is 0.77 ng/mL vs melanoma patients 1.73 ng/mL [Results]. Abstract #4 further teaches that melanoma patients with a high sPD-L1 at baseline (2.1 vs. 1.1 ng/mL) had clinical benefit (OR/PR/SD) after 4 cycles of pembrolizumab treatment [Results].
In regards to claims 10, 11, 21-22, and 26, Dronca et al teaches the subject is 60 patients with melanoma [Methods].
Applicant’s Arguments:
Applicant states, … nor does the combination of cited references teach or suggest a method that includes (a) measuring the level of one or more markers in a biological sample obtained from a mammal, (b) comparing the measured level of the one or more markers to a threshold level, (c) when the measured level is equal to or greater than the threshold level, performing TPE on the mammal, and subsequently (d) administering an immunotherapy to the mammal, where the one or more markers comprise soluble PD-L1 or evPD-L1, as recited by present claim 12.
In fact, it is only by using Applicant's specification (which demonstrates that TPE can significantly reduce plasma soluble PD-L1 levels and further teaches that TPE can be used to improve responsiveness to immunotherapy in cancer patients in need thereof by reducing the ability of soluble PD-L1 to decrease immunotherapy effectiveness) as a roadmap that one of ordinary skill in the art would be motivated to perform TPE and subsequently administer an immunotherapy to a mammal identified as having cancer and a level of soluble PD-L1 or evPD-L1 that is equal to or greater than a threshold level.
Examiner’s Response:
Applicant states, “nor does the combination of cited references teach or suggest a method that includes (a) measuring the level of one or more markers in a biological sample obtained from a mammal”
Eliaz et al teaches performing TPE to remove elevated gal-3 because it interferes or suppresses antineoplastic regimens, such as chemotherapeutic treatments [0011 & 0014].
Applicant further states, “(b) comparing the measured level of the one or more markers to a threshold level, (c) when the measured level is equal to or greater than the threshold level, performing TPE on the mammal,”
Eliaz et al teaches a patient whose condition could be improved by plasmapheresis would most likely obtain added therapeutic benefit from removal of other abnormally elevated or potentially harmful substances or agents found in the plasma [0033].
Applicant further states, “and subsequently (d) administering an immunotherapy to the mammal”.
Eliaz et al teaches removal of the elevated protein from circulation improves existing medical treatments [0011].
Dronca et al further teaches soluble PD-L1 is biologically active and capable of triggering apoptosis in activated T-cells [Background].
Abstract #4 teaches tumor-derived PD-L1 has additional systemic effects through the release of biologically active soluble forms of PD-L1 into the circulation, which further impedes the anti-tumor immune response and contributes to poor clinical outcomes in multiple myeloma patients [Background].
One of ordinary skill in the art, before the effective filing date, would have been motivated to combine Eliaz’s methods of treating patients by performing a TPE on a patient with a marker in a biological sample is equal to or higher than a threshold level and administering an immunotherapy, with Dronca’s method of soluble PD-L1 being biologically active and triggering apoptosis in activated T-cells in melanoma patients undergoing anti-PD-1 therapy, with Abstract #4 method of observing soluble PD-L1 impeding anti-tumor responses and contributing to poor clinical outcomes. The idea of combining them flows logically from their having been individually taught in the prior art (MPEP 2144.06). Combining prior art elements according to known methods to yield predictable results is an exemplary rationale for a prima facie case of obviousness. MPEP2143. It would have been prima facie obvious to combine Eliaz, Dronca, and Abstract #4’s methods to arrive at a method of performing TPE on a mammal identified as having equal or elevated soluble PD-L1 compared to a threshold level, and administering immunotherapy, because Eliaz teaches removing components using TPE that suppress or interfere with medications, and Dronca teaches soluble PD-L1 triggering apoptosis in activated T-cells. Furthermore, Abstract #4 teaches that soluble PD-L1 impedes anti-tumor response and contributes to poor clinical outcomes.
Applicant states, “TPE can significantly reduce plasma soluble PD-L1 levels”.
Claims 1, 12, and 23 are written so there is no preference on the marker the TPE is performed on, merely that a TPE is performed when soluble PD-L1 is equal or higher than a threshold.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DENNIS JOHN SULLIVAN whose telephone number is (571)272-0509. The examiner can normally be reached Mon - Fri: 7:30AM - 4:30PM.
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/DENNIS J SULLIVAN/Examiner, Art Unit 1642
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642
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