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 .
Election/Restrictions
Applicant’s election without traverse of Group I, , in the reply filed on 07/15/2026 is acknowledged.
Claims 24, 26, 30, 32-33, 37, 39, 43, and 45-46 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 07/15/2026.
Priority
The present application filed on 10/05/2023, is a 371 of PCT/US2022/032950, filed on 06/10/2022, and claims benefit of U.S. Provisional Application No. 63/209,217, filed on 10/10/2021.
The limitations recited in claims 1, 6, 7, 11, 13, 17, 19, and 20, of elected Group I, are supported in the original disclosure provided in U.S. Provisional Application No. 63/209,217, filed on 10/10/2021, thus instant claims 1, 6, 7, 11, 13, 17, 19, and 20, of elected Group I, have an effective filing date of 10/10/2021.
The limitation(s) in claim 2, reciting “detecting a population of oligoclonal antibodies specific for a platelet factor 4 (PF4) polypeptide in a sample obtained from a mammal” and “identifying the presence of said population of oligoclonal antibodies specific for said PF4 polypeptide based on a peak in the spectrum corresponding to the monoclonal antibodies specific for said PF4 polypeptide” are not supported in the original disclosure provided in U.S. Provisional Application No. 63/209,217, filed on 10/10/2021, but is supported in the PCT/US2022/032950, filed on 06/10/2022, thus instant claim 2 has an effective filing date of 06/10/2022.
Information Disclosure Statement
One Information Disclosure Statement(s) (IDS), filed on 12/11/2024, is acknowledged and considered.
Claim Status
Claims 1-2, 6-7, 11, 13, 17, 19-20, 24, 26, 30, 32-33, 37, 39, 43, and 45-46 are pending. Claims 24, 26, 30, 32-33, 37, 39, 43, and 45-46 are withdrawn as being drawn to a nonelected invention. Claims 3-5, 8-10, 12, 14-16, 18, 21-23, 25, 27-29, 31, 34-36, 38, 40-42, and 44 are cancelled. Claims 1-2, 6-7, 11, 13, 17, and 19-20 are examined herein below.
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.
Claim 11, 13, 17, and 20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because the claimed invention is directed to an abstract idea without significantly more.
The claimed invention is directed to a law of nature (natural phenomenon/correlation) without significantly more. The claim(s) recite(s) “detecting…a presence or absence of a population of monoclonal antibodies… classifying said mammal as having monoclonal gammopathy of thrombotic/thrombocytopenic significance (MGTS) if said presence of said population is detected and classifying said mammal as not having MGTS if said absence of said population level is detected.” This judicial exception is not integrated into a practical application because the additional elements amount to insignificant extra-solution activities. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because immunopurification and detection of the recited antibodies is well-known in the art.
The U.S. Patent and Trademark Office recently revised the MPEP with regard to § 101
(see the MPEP at 2106). Regarding the MPEP at 2106, in determining what concept the
claim is “directed to,” we first look to whether the claim recites:
(1) any judicial exceptions, including certain groupings of abstract ideas (i.e.,
mathematical concepts, certain methods of organizing human activity such as a fundamental
economic practice, or mental processes); and
(2) additional elements that integrate the judicial exception into a practical application
(see MPEP § 2106.05(a)-(c), (e)-(h)). Only if a claim
(1) recites a judicial exception and
(2) does not integrate that exception into a practical application, do we then look
to whether the claim contains an “‘inventive concept’ sufficient to ‘transform’” the
claimed judicial exception into a patent-eligible application of the judicial exception.
Alice, 573 U.S. at 221 (quoting Mayo, 566 U.S. at 82). In so doing, we thus consider
whether the claim:
(3) adds a specific limitation beyond the judicial exception that is not “well-
understood, routine, conventional” in the field (see MPEP § 2106.05(d)); or
(4) simply appends well-understood, routine, conventional activities previously
known to the industry, specified at a high level of generality, to the judicial exception.
See MPEP 2106.
ELIGIBILITY STEP 2A: WHETHER A CLAIM IS DIRECTED TO A
JUDICIALEXCEPTION
Step 2A, Prong 1
Claim 11 recites “detecting…a presence or absence of a population of monoclonal antibodies… classifying said mammal as having monoclonal gammopathy of thrombotic/thrombocytopenic significance (MGTS) if said presence of said population is detected and classifying said mammal as not having MGTS if said absence of said population level is detected,” which is drawn to a method wherein a correlation between detecting the presence of a naturally occurring biomarker with a diagnosis is made, and is, thus, directed to a law of nature, namely a natural phenomenon/correlation.
Step 2A, Prong 2
The judicial exceptions are not integrated into a practical application because the additional elements of reciting potential thrombotic and/or thrombocytopenic diagnostic conditions (claim 13), immunopurifying prior to detecting (claim 17), reciting serum type for performing the method (claim 19), and specifying the subject type (claim 20) are insignificant extra-solution activities, namely data-gathering steps, that do not add meaningful limitations to the judicial exception.
ELIGIBILITY STEP 2B: WHETHER ADDITIONAL ELEMENTS AMOUNT TO
SIGNIFICANTLY MORE THAN THE JUDICIAL EXCEPTION (INVENTIVE CONCEPT)
Step 2B
The instant claims do not include additional elements that are sufficient to amount to significantly more than the judicial exceptions because, at the time of filing, immunopurifying and detecting the presence of monoclonal antibodies specific for PF4 polypeptide was well-known, routine, and conventional in the art. For instance, Khandelwal teaches immunopurifying detecting a population of monoclonal antibodies with binding specificity for a PF4 polypeptide to assess the risk of a subject developing a thrombotic and/or thrombocytopenic condition, such as Immune heparin-induced thrombocytopenia (HIT), and for treating patients diagnosed the aforementioned condition (Khandelwal et al., WO 2020047170 A1: paras 003; 0008; 0063-0064; 0067; 0091, 0095). Further, Newman teaches the condition HIT is associated with antibodies directed against PF4 and heparin. Newman further teaches immunopurifying and detecting antibodies specific for PF4, which confirmed that HIT antibodies bind PF4, to better understand the role of these anit-PF4 antibodies in HIT pathophysiology (see Newman et al., Heparin-induced thrombocytopenia: new evidence for the dynamic binding of purified anti-PF4–heparin antibodies to platelets and the resultant platelet activation, 2000, Blood, 96, 1, 182-187).
For the reasons stated above, claims 11, 13, 17, and 20 stand rejected as being directed to a law of nature (natural phenomenon/correlation) without additional elements that amount to significantly more.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 11, 13, 17, and 19-20 is/are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Khandelwal et al., (WO 2020047170 A1, Date: 03/05/2020, provided in IDS filed on 12/11/2024, FOR Cite No. 2).
Throughout the disclosure, Khandelwal teaches methods for determining the risk of developing complement activation by protein/heparin binding complexes in a subject, determining the presence of complement activation by protein/heparin binding complexes in a subject, and treating diseases including heparin-induced thrombocytopenia (HIT) in a subject.
Regarding claim 11, Khandelwal teaches a method for assessing a mammal having a thrombotic and/or thrombocytopenic condition, wherein said method comprises:(a) detecting, in a sample from said mammal, a presence or absence of a population of monoclonal antibodies having binding specificity for a PF4 polypeptide (paras 003; 0008; 0063-0064; 0067; 0091, 0095); (b) classifying said mammal as having monoclonal gammopathy of thrombotic/thrombocytopenic significance (MGTS) if said presence of said population is detected (para 0091); and (c) classifying said mammal as not having MGTS if said absence of said population level is detected (para 0091).
Regarding claim 13, Khandelwal teaches the method of claim 11, wherein said thrombotic and/or thrombocytopenic condition is selected from the group consisting of heparin-induced thrombocytopenia (HIT), HIT with thrombosis, delayed-onset HIT, flush-related HIT, persistent HIT, HIT with disseminated intravascular coagulation, refractory HIT, spontaneous HIT with thrombosis, spontaneous HIT without thrombosis, and vaccine-induced immune thrombotic thrombocytopenia (VITT) [para 00101].
Regarding claim 17, Khandelwal teaches the method of claim 11, wherein said method comprises, prior to said detecting, immunopurifying said sample for antibodies specific for said PF4 polypeptide (para 00109-00115).
Regarding claim 19, Khandelwal teaches the method of claim 11, wherein said sample is a serum sample or a plasma sample (para 0014).
Regarding claim 20, Khandelwal teaches the method of claim 11, wherein said mammal is a human (para 0066).
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.
Claim(s) 1 and 6-7 are rejected under 35 U.S.C. 103 as being unpatentable over Khandelwal et al., (WO 2020047170 A1, Date: 03/05/2020, provided in IDS filed on 12/11/2024, FOR Cite No. 2) in view of Murray et al., (US 10,267,806 B2, Date: 04/23/2019).
Regarding claim 1, the teaching of Khandelwal are discussed herein above. Khandelwal teaches a method for detecting a population of monoclonal antibodies specific for a platelet factor 4 (PF4) polypeptide in a sample obtained from a mammal, said method comprising: immunopurifying antibodies specific for said PF4 polypeptide from the sample (paras 003; 0008; 0063-0064; 0066-0067; 0091-0092, 0095; 00101; 00109 (incorporated reference Raova L, et al., teaches immunopurifying); and 00115). Khandelwal does not teach subjecting the immunopurified immunoglobulins to a mass spectrometry technique to obtain a mass spectrum of the sample and identifying the presence of said population of monoclonal antibodies specific for said PF4 polypeptide based on a peak in the spectrum corresponding to the monoclonal antibodies specific for said PF4 polypeptide.
Throughout the disclosure, Murray teaches methods for immunopurifying immunoglobulin isotypes then using mass spectrometry techniques to detect and quantify the isolated or target immunoglobulin isotype(s). Murray teaches some embodiments comprise immunopurifying a population of antibodies, classified under one of the known isotypes, from a mammal that is human followed by detecting said population of antibodies, identifying corresponding peaks of antibodies in a mass spectrum, and quantifying said antibodies detected.
Murray teaches the limitation(s) of claim 1 reciting subjecting the immunopurified immunoglobulins to a mass spectrometry technique to obtain a mass spectrum of the sample and identifying the presence of said population of monoclonal antibodies specific for a target analyte based on a peak in the spectrum corresponding to the monoclonal antibodies specific for target analyte (col. 2, lines 6-19; col. 32, lines 1-13; col. 4, lines 17-20).
It would have been prima facie obvious, at the time of filing, to combine the method of detecting monoclonal antibodies specific for PF4 polypeptide, as taught by Khandelwal, with method of immunopurifying followed by identifying the immunopurified immunoglobulins using mass spectroscopy, as taught by Murray. A skilled artisan would have been motivated to combine these teachings in order to substitute the detection method of Khandelwal with the detection method of Murray because it enable detection and quantification of specific isotypes of the immunopurified monoclonal antibodies specific for PF4 polypeptide. A person having ordinary skill in the art would have a reasonable expectation of success because combining these teachings amounts to combining known elements and methods, known to perform and be performed the same when separated as when combined, to yield expected and predictable results.
Regarding claim 6, Khandelwal teaches the method of claim 1,wherein said sample is a serum sample or a plasma sample (para 0014).
Regarding claim 7, Khandelwal teaches the method of claim 1,wherein said mammal is a human (para 0066).
Claim(s) 2 is rejected under 35 U.S.C. 103 as being unpatentable over Amiral et al., (Amiral et al., Affinity purification of heparin-dependent antibodies to platelet factor 4 developed in heparin-induced thrombocytopenia: biological characteristics and effects on platelet activation, 2000, British Journal of Haematology, 109, 336-341), in view of Murray et al., (US 10,267,806 B2, Date: 04/23/2019).
Throughout the article, Amiral teaches a study where affinity chromatography was used to immunopurify antibodies specific to heparin platelet factor 4 (H-PF4) complexes present in the plasma of patients diagnosed with heparin-induced thrombocytopenia (HIT). Amiral teaches using an enzyme-linked immunosorbent assay (ELISA) to detect the antibodies specific to PF4, which displayed different characteristics. Amiral further teaches the hypothesis that HIT antibodies specific to PF4 are heterogeneous with respect to their affinity and specificity for target antigens, which may strongly influence their ability to activate platelets and their role in HIT pathogenicity.
Regarding claim 2, Amiral teaches method for detecting a population of oligoclonal antibodies specific for a platelet factor 4 (PF4) polypeptide in a sample obtained from a mammal, said method comprising: immunopurifying antibodies specific for said PF4 polypeptide from the sample (pgs. 337-339 and pg. 339, full para 1). Amiral does not teach subjecting the immunopurified immunoglobulins to a mass spectrometry technique to obtain a mass spectrum of the sample and identifying the presence of said population of oligoclonal antibodies specific for said PF4 polypeptide based on a peak in the spectrum corresponding to the monoclonal antibodies specific for said PF4 polypeptide.
The teachings of Murray are discussed herein above. Murray teaches the limitations of claim 2 reciting subjecting the immunopurified immunoglobulins to a mass spectrometry technique to obtain a mass spectrum of the sample and identifying the presence of said population of monoclonal antibodies specific for a target analyte based on a peak in the spectrum corresponding to the monoclonal antibodies specific for target analyte (col. 2, lines 6-19; col. 32, lines 1-13; col. 4, lines 17-20). Murray does not teach oligoclonal antibodies.
It would have been prima facie obvious, at the time of filing, to combine the method of detecting oligoclonal antibodies specific for PF4 polypeptide, as taught by Amiral, with method of identifying immunopurified immunoglobulins using mass spectroscopy, as taught by Murray. A skilled artisan would have been motivated to combine these teachings in order to substitute the detection method of Amiral with the detection method of Murray because it enable detection and quantification of specific isotypes of the immunopurified oligoclonal antibodies specific for PF4 polypeptide. Further, at the time of filing, the prior art taught that only some anti-PF4 antibodies, including a population of oligoclonal anti-PF4 antibodies, are responsible for in vivo cell activation and subsequent thrombocytopenia and clinical complications observed in subjects diagnosed with HIT (see Amiral et al.). Thus, at the time of filing, a skilled artisan would have been further motivated to combine these teachings in order to immunopurify, detect, and quantify oligoclonal antibodies specific for PF4 polypeptides because it would enable diagnosis of a thrombocytopenic condition. At the time of filing, a person having ordinary skill in the art would have a reasonable expectation of success because combining these teachings amounts to combining known elements/methods, known to have the same function and/or known to be performed the same when separated as when they are combined, to yield expected and predictable results.
Conclusion
All examined claims (1-2, 6-7, 11, 13, 17, and 19-20) are rejected. No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MELISSA L LIRIANO-NG whose telephone number is (571)272-0085. The examiner can normally be reached Monday-Friday, 7:30 am-3:30 pm (EST).
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Bao-Thuy Nguyen can be reached at (571)272-0824. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MELISSA LIZETTE LIRIANO-NG/Examiner, Art Unit 1677
/BAO-THUY L NGUYEN/Supervisory Patent Examiner, Art Unit 1677 August 10, 2026
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