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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 12/29/2025 has been entered.
Claims 27-29, 32 and 35 and new claims 36-38 are under consideration in the instant Office Action.
Withdrawn Rejection
The rejection of claims 26-29, 32 and 35 on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 9, 12-13, and 22-25 of copending Application No. 17/945,058 is withdrawn in view of newly amended claims and new claim amendments in ‘058.
New Rejections Necessitated by Amendment
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.
Claim 37 is 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.
The term “purity” in claim 37 is a relative term which renders the claim indefinite.
The term “purity” 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. The general meaning of the
term “purity: is understood to be “freedom from adulteration or contamination”. The use
of this term in the claim is indefinite because it is used as a comparison so there are no
clear metes and bounds by what “purity” is claiming.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 36-37 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
See MPEP §2163(I)(A) which states: "The claimed invention as a whole may not be adequately described where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art recognized correlation or relationship between the structure of the invention and its function. A biomolecule sequence described only by a functional characteristic, without any known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.”
New claim 37 calls for an “agent” and this term encompasses an antibody, a lectin, a ligand, a soluble receptor, a binding protein or an oligonucleotide. There is no structural requirement for the agents in new claim 37 beyond function of the agent forming a vesicle-agent complex and only requires that “the agent” is an antibody, a lectin, a ligand, a soluble receptor, a binding protein or an oligonucleotide as set forth in the instant specification at [0007]. The claimed function can be achieved in any form as long as the purity of the vesicles are greater than the vesicle purity in the biological sample. The instant claims do not require that the “agent” or an antibody, a lectin, a ligand, a soluble receptor, a binding protein or an oligonucleotide possess any particular conserved structure or other disclosed distinguishing feature. Therefore, the genera are merely defined by function and the instant specification fails to describe the full genera of molecules that are encompassed by these claims that an agent as in instant claim 37. The instant specification fails to teach any other agents beyond antibodies, lectin, ligand a soluble receptor, a binding protein or an oligonucleotide or lytic agents.
Dependent claim 37 requires an “agent”. There is no structural requirement for the agents beyond function. This can be achieved in any form as long as the agent acts upon a vesicle. The instant specification discloses only specific agents but no other agents. The claims do not require that the “agent” possess any particular conserved structure or other disclosed distinguishing feature. The term “agent” encompasses many things including antibodies, proteins, peptides, small drugs or other drugs. While the new claim 37 now requires an antibody, a lectin, a ligand, a soluble receptor, a binding protein or an oligonucleotide, these are still generic genera without any specific structure. Thus the claims are drawn to a genus of molecules that are defined only by their function or a generic genera. Therefore, the genus is merely defined by function and the instant specification fails to describe the full genus of molecules that are encompassed by these claims. The specification does not describe anything beyond a limited number of specific genera.
To provide adequate written description and evidence of possession of claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In the instant case, the only factors present in the claims are a recitation of prospective activity. There is not even identification of any particular portion of the structure that must be conserved for said activity. The specification does not provide a complete structure of all fragments and agents and fails to provide a representative number of species for the recited genera. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genera.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that they invented what is claimed.” (See Vas-Cath at page 1116).
While the instant specification discloses specific genera of antibodies, as in [007] and [0011], these genera of antibodies are not specific and very generic. Therefore, the skilled artisan cannot envision the detailed chemical structure of the encompassed agents or generic antibody, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The product itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF's were found to be unpatentable due to lack of written description for that broad class. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
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 27-29, 32, 35 and new claims 36-38 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural correlation without significantly more. The claims recite a natural correlation between neuro-derived vesicles from a subject suspected of having Alzheimer’s disease or another neurological disease wherein the biological sample is obtained from blood and has synaptophysin as a biomarker as now claimed in new independent claim 36. This judicial exception is not integrated into a practical application because the claimed method only class for the collection of data and making an observation of the biomarker levels in neuro-derived vesicles from a subject suspected of having Alzheimer’s disease or another neurological disease. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims do not require more than the mere observation of the natural correlation between the levels of biomarkers in neuron-derived vesicles and Alzheimer’s disease or other neurological diseases.
The subject matter eligibility under 35 U.S.C. 101 of natural products (i.e., whether the claimed product is a non-naturally occurring product of human ingenuity that is markedly different from naturally occurring products) was confirmed by the U.S.
Supreme Court decisions including Association for Molecular Pathology v. Myriad Genetics, Inc., 569 U.S. _, 133 S. Ct. 2107, 2116, 106 USPQ2d 1972 (2013), and Mayo Collaborative Services v. Prometheus Laboratories, Inc., 566 U.S. _, 132 S. Ct. 1289, 101 USPQ2d 1961 (2012). "[L]aws of nature, natural phenomena, and abstract ideas"
are not patentable. Diamond v. Diehr, 450 U. S. 175, 185 (1981); see also Bilski v. Kappos, 561 U. S. __, __ (2010) (slip op., at 5). "Phenomena of nature, though just discovered, mental processes, and abstract intellectual concepts are not patentable, as they are the basic tools of scientific and technological work." Gottschalkv. Benson, 409 U. S. 63, 67 (1972).
In brief, in Prometheus, a method of optimizing therapeutic efficacy for treatment
of an immune-mediated gastrointestinal disorder is the focus. This method comprises a) administering 6-thioguanine to patients and b) determining the level of 6-thioguanine in the patients and c) correlate the level of 6-thioguanine, i.e. a certain level/red blood cells, with the decision whether a need for increase or decrease the amount of 6-
thioguanine treatment in said patients.
In Prometheus, the Court found that "[i]f a law of nature is not patentable, neither is a process reciting a law of nature, unless that process has additional features that provide practical assurance that the process is more than a drafting effort designed to monopolize the law of nature itself." Additionally, "conventional or obvious" "[pre]solution activity" is normally not sufficient to transform an unpatentable law of nature into a patent-eligible application of such a law". Flook, 437 U. S., at 590; see also Bilski, 561 U. S., at __ (slip op., at 14) ("[T]he prohibition against patenting abstract ideas 'cannot be circumvented by'.., adding 'insignificant post-solution activity'" (quoting Diehr, supra, at 191-192)).
The Court also summarized their holding by stating "[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately."
Thus, if the claim recites or involves a judicial exception, such as a law of nature/natural principle or natural phenomenon (e.g., the law of gravity, F=ma, sunlight, barometric pressure, etc.), and/or something that appears to be a natural product (e.g., a citrus fruit, uranium metal, nucleic acid, protein, etc.), then the claim only qualifies as eligible subject matter if the claim as a whole recites something significantly different than the judicial exception itself.
In the instant case, based upon an analysis with respect to the claim as a whole, claims 27-29, 32, 35 and new claims 36-38 are determined to be directed to a judicial exception without significantly more. The rationale for this determination is explained below in view of controlling legal precedent set forth in 2014 Interim Guidance on Patent Subject Matter Eligibility (79 FR 74618) dated December 16, 2014 and 2019 Revised Patent Subject Matter Eligibility Guidance (84 FR 50) dated January 07, 2019.
The instant claims 27-29, 32, 35 and new claims 36-38 encompass a process. (Step 1: Yes).
Next, Step 2, is the two-part analysis from Alice Corp. (also called the Mayo test) to determine whether the claim is directed to laws of nature, natural phenomena, and abstract ideas (the judicially recognized exceptions). (In Alice Corp. v. CLS Bank Int’l, 134 S. Ct. 2347, 2354 (2014) the Supreme Court sets forth a two-step test for determining patent eligibility. First, determine if the claims encompass a judicial exception (a natural phenomenon/law of nature/abstract idea). If so, then ask whether the remaining elements/steps, either in isolation or combination with the other non-patent-ineligible elements, are sufficient to ‘“transform the nature of the claim’ into a patent-eligible application.” Id. at 2355 (quoting Mayo, 132 S. Ct. at 1297). Put another way, there must be a further “inventive concept” to take the claim into the realm of patent eligibility. Id. at 2355. In the recent Myriad v Ambry case, the CAFC found claims (drawn to methods comprising obtaining tissue samples, analyzing sequences of cDNA and comparing germline sequences of a gene to wild-type sequences) to encompass the abstract mental processes of ‘comparing’ and ‘analyzing’. Recitation of specific techniques (in Myriad claims 7 and 8 further recited hybridization and PCR) were deemed not “enough” to make the claims patent-eligible since the claims contained no otherwise new process. The elements/steps recited in addition to the judicial exception did nothing more than spell out what practitioners already knew). The instant claims 27-29, 32, 35 and new claims 36-38 encompass obtaining biomarkers in neuro-derived vesicles biological samples from suspected Alzheimer’s subject during pathology of Alzheimer’s disease, the process that is governed by a law of nature, and thus is a judicial exception. The biomarkers in neuro-derived vesicles biological samples are naturally occurring factors, which, as evidenced by the claims and the specification as filed, are present naturally in AD populations. Thus, the relation between the presence and levels biomarkers in neuro-derived vesicles and pathology of Alzheimer’s disease exists in principle and is a consequence of the ways these factors are metabolized by the body, entirely natural process, a natural phenomenon, and thus a judicial exception (Step 2A/1: Yes).
Next, prong two of Step 2A requires identifying whether there are additional elements recited in the claim beyond the judicial exception(s) and evaluating those additional elements to determine whether they integrate the exception into a practical application of the exception. “Integration in to a practical application” requires an additional element or combination of additional elements in the claim to apply, rely on, or use the judicial exception in a manner that imposes a meaningful limit on the judicial exception, such as the claim is more than a drafting effort designed to monopolize the exception. In the instant case, there is no need to administer specific treatment when a patient is identified no matter what levels are reported. Therefore, embodiment of instant claim 36 does do not recite any additional elements to integrate the judicial exception into a practical application because all the steps of the claimed methods are limited to only those that measure naturally occurring factors during a naturally occurring pathology. (Step 2A/2: No in part). The Court also summarized their holding by stating "[t]o put the matter more succinctly, the claims inform a relevant audience about certain laws of nature; any additional steps consist of well understood, routine, conventional activity already engaged in by the scientific community; and those steps, when viewed as a whole, add nothing significant beyond the sum of their parts taken separately." Thus, if the claim recites or involves a judicial exception, such as a law of nature/natural principle or natural phenomenon (e.g., the law of gravity, F=ma, sunlight, barometric pressure, etc.), and/or something that appears to be a natural product (e.g., a citrus fruit, uranium metal, nucleic acid, protein, etc.), then the claim only qualifies as eligible subject matter if the claim as a whole recites something significantly different than the judicial exception itself.
Finally, claims 27-29, 32, 35 and new claims 36-38 do not recite any elements, or combinations of elements to ensure that the claim as a whole amounts to significantly more than the judicial exception because the active steps of the claims – collecting biological samples, measuring the level of biomarkers in neuron-derived vesicles − represent routine steps that are recited at a high level of generality and encompass well-understood and purely conventional routine techniques in the art, as shown by Goetzl US2015/0119278 (3/13/2024 PTO-892),Joyce et al., WO2015/130956 (7/31/2024, PTO-892) and Marquez-Sterling et al., 1997 (4/7/2025 PTO-892) as discussed below. The claims are ineligible because claims reciting elements/steps in addition to the judicial exception at a high level of generality such that substantially all practical applications of the judicial exception are covered. Claims reciting elements/steps in addition to the judicial exception that are well-understood, purely conventional or routine in the relevant field; that are insignificant extra-solution activity, e.g., are merely appended to the judicial exception(s); and that amount to nothing more than a mere field of use.
Note that recited further biomarkers in instant claim 32 cannot add significantly more to satisfy step 2B (Step 2B: No).
Thus for reasons fully explained above, claims 27-29, 32, 35 and new claims 36-38 not satisfy the requirement of 35 U.S.C. 101 and are therefore rejected.
Modified Rejection Necessitated by Amendment
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.
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 27-29, 32, 35 and new claims 36-38 are rejected under 35 U.S.C. 103 as being unpatentable over Goetzl US2015/0119278 (3/13/2024 PTO-892) in view of Joyce et al., WO2015/130956 (7/31/2024, PTO-892) and Marquez-Sterling et al., 1997 (4/7/2025 PTO-892).
Goetzl teaches methods of diagnosing or prognosing neurodegenerative disorders in a subject by obtaining biological samples from the subject and measuring the levels of biomarkers wherein the method comprising isolating vesicles from the biological sample (see paragraph 5) as in instant new claim 36. Goetzl teaches that vesicles are selected from the group of exosomes, microparticles, macrovesicles, nanosomes, extracellular vesicles, and ectosomes (see paragraph 5) as in instant claim 27. Goetzl teaches that the isolated exosomes are selected from the group consisting of neuron derived exosomes, astrocyte-derived exosomes, oligodendrocyte-derived exosomes, and microglia-derived exosomes (see paragraph 5) as in instant claim 28. Goetzl teaches that the level of one or more biomarkers is the protein, phosphorylated protein, mRNA, or miRNA level of the one or more biomarker (see paragraph 5) as in instant claim 29. Goetzl teaches that the samples are selected from whole blood, serum, plasma, urine and cerebrospinal fluid (see paragraph 5) as in instant claims 36 and 38. Goetzl teaches that the isolating vesicles from a biological sample comprises: contacting the biological sample with an agent under conditions wherein a vesicle present in said biological sample binds to said agent to form a vesicle-agent complex; and isolating said vesicle from said vesicle-agent complex to obtain a sample containing said vesicle, wherein the vesicles present in said sample is greater than the vesicles present in said biological sample (see paragraph 6) as in instant claims 36-37. Goetzl teaches that at least one of the one or more biomarkers are selected from the group consisting of Tau, phosphorylated Tau, Ab1-42, TDP-43,a-synuclein, SOD-1, FUS, FKBP51, IRS-1, phosphorylated IRS-1, cathepsin D (CTSD), type 1 lysosome-associated membrane protein (LAMP1), ubiquitinylated proteins (UBP), heat-shock protein 70 (HSP70), neuron-specific enolase (NSE), neurofilament light chain (NFL), CD9, CD63, CD81, and CD171 (see paragraph 6) as in instant claim 32.
Goetzl teaches that the agent is an antibody and that the antibody is a monoclonal anti human NCAM antibody; a monoclonal CD171 antibody; a monoclonal anti-human CD171 antibody; a monoclonal CD9 antibody; a monoclonal CD63 antibody; and a monoclonal CD81 antibody (see paragraph 6) as in instant claim 36. Goetzl teaches that the biomarker is measured by a method selected from the group consisting of immunohistochemistry, immunocytochemistry, immunofluorescence, immunoprecipitation, western blotting, and ELISA (see paragraphs 39 and 45) as in instant claim 35. Goetzl does not specifically teach the required biomarker of new claim 36, synaptophysin.
Joyce teaches methods for isolating, measuring, detecting and analyzing extracellular vesicles, such as exosomes, which contain biomarkers including peptides, protein and or nucleic acids that indicate brain diseases like Alzheimer’s disease (see paragraphs 2, 10, 14, 17, 41, 253, 277) as in instant claims 27 and 29. Joyce teaches that the exosomes are derived specifically from brain cells (see paragraph 2, 277) and reads on the exosomes of claim 28 since neurons, astrocytes, oligodendrocytes and microglia are all brain derived cells. Joyce also teaches that the antigens on the exosomes include tau, beta amyloid, neurons specific enolase, NFL and synaptophysin (see paragraph 2, 17, 41, 236, 277, 286) as in instant claims 36 and 32. Joyce teaches that the biological samples include whole blood, plasma and serum (see paragraphs 40, 207, 253, 277, 286 ) as in instant claims 36-37. Joyce teaches using enzyme linked assay like and ELISA for quantitative analysis of the amount of a biomarker (see paragraphs 159, 189-190, 198) as in instant claim 35. Joyce teaches that biomarker synaptophysin is found in exosomes isolated from biological samples that include blood, serum or plasma and are biomarkers for diseases like Alzheimer’s diseases as in instant claims 36, 27-28.
Marquez-Sterling teaches that vesicles purified from brains have the recycling synaptic vesicle integral membrane proteins synaptophysin, synaptotagmin and SV2 (see abstract) as in instant claim 36. Marquez-Sterling teaches that the APP protein that is a precursor to amyloid beta in internalized with recycling synaptic vesicle integral membrane proteins (see page 140, 2nd column, 2nd paragraph). Marquez-Sterling teaches immunoisolation of synaptic vesicle using synaptophysin beads and immunocytochemistry to detect synaptophysin, synaptotagmin and SV2 proteins (see page 143, 2nd column and page 144, 2nd column, 1st paragraph) as in instant claims 36 and 35. Marquez-Sterling does not teach the instantly claimed method.
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of Goetzl, Joyce and Marquez-Sterling. The person of ordinary skill in the art would have been motivated to make and use the invention as claimed because both Goetzl and Joyce teach methods of measuring biomarker levels to determine the status of an Alzheimer’s patient and Marquez-Sterling teaches that synaptophysin, synaptotagmin and SV2 are biomarkers used to identify synaptic vesicles. Therefore, it would be obvious to use the synaptophysin, synaptotagmin and SV2 biomarker taught by Joyce and Marquez-Sterling since Joyce teaches that this biomarker is linked to AD diagnosis as are the methods and biomarkers taught by Goetzl. One of ordinary skill would be motivated to combine biomarkers known to be effective in diagnosing AD and identify synaptic vesicles and would have expected the combination of biomarkers be at least as good as biomarkers alone. The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
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 26-29, 32 and 35 and new claims 36-38 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 9,958,460 in view of Joyce et al., WO2015/130956 (7/31/2024, PTO-892) and Marquez-Sterling et al., 1997 (4/7/2025 PTO-892). ‘460 claims a method of analyzing a sample from a subject by obtaining a biological sample comprising vesicles from a subject, (ii) isolating vesicles from the biological sample, and (iii) detecting one or more biomarkers from the isolated vesicles, wherein at least one of the one or more biomarkers is selected from the group consisting of Tau, phosphorylated Tau, beta-amyloid 1-42 (Aβ1-42), transactive response DNA binding protein 43 (TDP-43), α-synuclein, superoxide dismutase 1 (SOD-1), FUS RNA binding protein (FUS), FK506 binding protein 51 (FKBP51), insulin receptor substrate 1 (IRS-1), phosphorylated IRS-1, cathepsin D (CTSD), lysosomal-associated membrane protein 1 (LAMP1), ubiquitinylated proteins (UBP), heat-shock protein 70 (HSP70), neuron specific enolase (NSE), and neurofilament light chain (NFL), wherein the biological sample is whole blood, serum, or plasma, and wherein the vesicles are selected from the group consisting of neuron-derived exosomes, astrocyte-derived exosomes, oligodendrocyte-derived exosomes, and microglia-derived exosomes; wherein the isolating vesicles from a biological sample comprises: contacting the biological sample with an agent under conditions wherein a vesicle present in said biological sample binds to said agent to form a vesicle-agent complex; and isolating said vesicle from said vesicle-agent complex to obtain a sample containing said vesicle and wherein the detection of one or more biomarkers is the detection of protein, phosphorylated protein, mRNA, or miRNA of the one or more biomarkers. These limitations read on the instant claims except that they do not claim the biomarker like synaptophysin or synaptotagmin found in exosomes as required in instant claim 26. Joyce and Marquez-Sterling make up for that deficiency. Joyce teaches biofluid markers for Alzheimer’s disease, a neurodegenerative disease (see abstract and paragraphs 14, 18) and Marquez-Sterling teaches that synaptic vesicles have synaptotagmin and synaptophysin as synaptic markers. ‘460 and Joyce teach methods of measuring biomarker levels to determine the status of an Alzheimer’s patient. Therefore, it would be obvious to use the synaptotagmin and synaptophysin biomarkers taught by Joyce and Marquez-Sterling since the references teach that these biomarkers are linked to identifying synaptic vesicles and are linked to AD diagnosis as are the methods and biomarkers taught by ‘460. One of ordinary skill would be motivated to combine biomarkers known to be effective in diagnosing AD and would have expected the combination of biomarkers be at least as good as biomarkers alone.
Response to Arguments
Applicant's arguments filed 12/29/2025 have been fully considered but they are not found persuasive. Applicant argues that the new limitation of synaptophysin in the new instant claim 36 makes them allowable because the Joyce reference fails to teach the other biomarkers. This is not found persuasive because both Joyce and Marquez-Sterling teaches the biomarkers, synaptotagmin and synaptophysin, and therefore, the instant claims are obvious over the prior art of record.
Applicant argues that their new claims 36-38 are identical to claims that were recently allowed by the European Patent Office. Applicant’s citation of previously granted patents is not persuasive regarding the prosecution of the present application, since each patent application is prosecuted on its own merits and what was done in a previous case does not constitute imprimatur for the prosecution of further cases. In re Gyurik, 596 F.2d 1012, 201 USPQ 552 (CCPA 1979); In re Attwood, 267 F.2d 954, 122 USPQ 378 (CCPA 1959); In re Freedlander, 136 F.2d 759, 760, 58 USPQ 402, 403 (CCPA 1943).
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). The combination of teachings in the prior art point to the fact that the claimed biomarkers as taught by the reference Goetzl and Joyce are known to be found in whole blood, serum and plasma. Joyce teaches that the biomarker synaptophysin is found in exosomes isolated from biological samples that include blood, serum or plasma and are biomarkers for diseases like Alzheimer’s diseases. Since Marquez-Sterling teaches immunoisolation of synaptic vesicle using synaptophysin beads and immunocytochemistry to detect synaptophysin, synaptotagmin and SV2 proteins (see page 143, 2nd column and page 144, 2nd column, 1st paragraph), it speaks to the idea that all of these biomarkers are found in whole blood, serum and plasma like the other biomarkers required in this type of assay. The combination of these teachings clearly show that one of ordinary skill in the art would have a reasonable expectation to look for all of these biomarkers in in whole blood, serum and plasma with a reasonable expectation of success.
Further, applicant’s argument that the Joyce reference does not contain empirical data is not found persuasive because Joyce clearly suggest that these biomarkers are found in the requires samples. Further, the Goetzl reference teaches methods of diagnosing or prognosing neurodegenerative disorders in a subject by obtaining biological samples from the subject and measuring the levels of biomarkers wherein the method comprising isolating vesicles from the biological sample (see paragraph 5) and that the samples are selected from whole blood, serum, plasma, urine and cerebrospinal fluid. Joyces teachings are not separate and isolated from the prior art but set forth in view of what is known in the prior art and what would be obvious to one of ordinary skill in the art and would be found reasonable in view of what is disclosed in the prior art. Examples may be “working” or “prophetic” as long as there reasonable exaptation of success provided by the teachings in the prior art, as already show above. Therefore, applicant’s arguments are not found persuasive.
Finally, applicant argues against the double patenting rejections with the same argument set forth for the 103 obvious rejection above. Therefore, they are not found persuasive for the reasons set forth above, and the rejections are maintained.
Conclusion
No claims are allowed.
Advisory Information
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AURORA M. FONTAINHAS whose telephone number is 571-272-2952. The examiner can normally be reached on Monday - Friday (8AM - 4PM).
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached on (571)272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675