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 .
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 7, 11, 14 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.
The term “early” in claim 7 is a relative term which renders the claim indefinite. The term “early detection of a disease or of a disease symptom” 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.
Claims 7 and 14 recites Table 1 and Table 2, respectively. Incorporation of Table 1 or Table 2 from the specification makes the claim not clear and is not typical in a claim. It is not clear as to exactly what elements of Table 1 and Table 2 are incorporated into claims 7 and 14, respectively. Moreover, the specification, including Table 1 and Table 2, is subject to amendment at any time, without amendment to any claim, though it would affect the scope of claims 7 and 14. For all those reasons, incorporating tables from the specification renders the claims not clear and susceptible to being even less clear should the specification and/or tables be amended.
Claim 11 recites “hyper-proliferative” state. The term “hyper-proliferative” is a relative term which renders the claim indefinite. The term “hyper-proliferative” 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.
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.
Claim 10 is 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 claims contain 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 pre-AIA the inventors, at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
Claim 1 requires an antibody or antigen binding fragment specific to EVs that binds to a target selected from CD81, CD9 and cD63, or both.
The specification does not describe which amino acid residues, nucleic acid residues or other molecular components are responsible for the functions claimed. Rather, the specification states that these potential agents are obtained through several techniques. Although the specification provides a few examples of potential generic agents, it fails to disclose the structures common to all members of the genus of peptides encompassed by the broad definition provided by applicant. The specification does not disclose the structure of all of the claimed variant agents and fails to disclose which regions of the agents are responsible for the functions claimed. In the absence of a known or disclosed correlation between structure and function, claims which encompass variants defined by their function are generally not considered described.
Applicant is directed to MPEP § 2163 for guidelines on compliance with the written description requirement. Here, applicant has not described a reasonable number of members of the genus of agents that bind to CD81, CD9, CD63, or both, or a nucleic acid fragment, i.e. the required starting materials for the claims, but rather has presented the public with an idea of how to obtain some binding agents that fall within the scope of the claim. The Court of Appeals for the Federal Circuit addressed claims of this sort in great detail in University of Rochester v. G.D. Searle and Co. (69 USPQ 2nd 1886, CAFC 2004). In Rochester, the Federal Circuit upheld the district court's ruling that patent claims which recited administration of compounds not disclosed, but rather to be identified in a screening assay, were invalid on their face.
Regarding the scope of the claims that includes antibodies that bind to CD81, CD9, CD63, or both, the specification does not describe the structure of the full genus of antibodies responsible for each of the functions claimed. The Federal Circuit has clarified Written Description as it applies to antibodies in the recent decision Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. 112(a) (or pre-AIA first paragraph) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called “newly characterized antigen” test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the “newly characterized antigen” test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad, 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of an antigen alone is not considered adequate written description of a claimed antibody to that antigen, even when preparation of such an antibody is routine and conventional. Id.
While generically the structure of antibodies is known, the structure of the presently recited antibodies can vary substantially within the above given claimed recitations. As noted in Amgen, knowledge that an antibody binds to a particular epitope on an antigen tells one nothing at all about the structure of the antibody, wherein “instead of analogizing the antibody-antigen relationship to a ‘key in a lock,’ it [is] more apt to analogize it to a lock and ‘a ring with a million keys on it.” (Internal citations omitted). The relevant antibody art confirms this quandary, indicating that “knowledge of an epitope or antigen used to generate a monoclonal antibody is insufficient for making the original antibody available, even if suitable in vitro test systems for screening are used.” See p. 8, lines 3-5 of WO 2009/033743 A1. Therefore, those of skill in the art would not accept that the inventor had been in possession of the full genus of antibodies presently claimed.
Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Abbvie Deutschland GMBH & Co. v. Janssen Biotech, Inc. (759 F.3d 1285 (Fed. Cir. 2014). “When a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the claimed result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus." Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005).
Consequently, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus of binding agents (including antibodies) nor guidance as to which of the myriad of molecules encompassed by the binding agents would meet the limitations of the claims. Further, given the well-known high level of polymorphism of immunoglobulins and antibodies, the skilled artisan would not have recognized that applicant was in possession of the vast repertoire of antibodies encompassed by the claimed invention.
Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111 (Fed. Cir. 1991), 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 [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
The skilled artisan cannot envision the detailed chemical structure of the genus of binding agents, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of identification. 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 compound 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 (Fed. Cir. 1991). Therefore, the instant claims do not meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
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 1-17 and 19-20 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (a natural law/correlation and abstract idea and mental step) without significantly more. The claim(s) recite(s) “(iii) determining in said population of EVs a presence of at least one factor indicative of said adverse cellular state”.
This judicial exception is not integrated into a practical application because none of the other steps amount to a practical application. Examiner notes that isolating step of (ii) in claim 1 is a data gathering step required to use the correlation that does not add a meaningful limitation to the method as it is an insignificant extra-solution activity. Similarly, the further isolating total EVs from the sample before step (ii) as recited in claim 8 is also a data gathering step that does not amount to a practical application as it is an insignificant extra-solution activity. Also, the step of selecting a subject who suffers from a disease, as recited in claim 16, is also an insignificant extra-solution activity. The remaining limitations regarding the specific factor indicative of adverse cellular state, or the type of antibody used, or type of disease activity or pathological condition that is determined, all relate to the natural law or natural correlation between the antibody or fragment and the disease activity or pathological condition, and therefore such limitations, being part of the judicial exception itself, cannot amount to a practical application of the judicial exception. Regarding claim 19 and the comparison of the determining step (iii) of claim 1 before a time point before treatment for a disease and the recitation of a decrease in adveser cellular state being indicative of responsiveness to the treatment, these limitations are directed to a judicial exception (a natural law or correlation), and therefore do not amount to a practical application. Moreover, the treatment steps recited in claim 20 is not specific enough to amount to a practical application. [Claim 21 appears to recite a treatment that is specific enough to amount to a practical application.]
Furthermore, the rejected claim(s) 1-17 and 19-20 does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the steps, such as the determining the presence of a factor indicative of an adverse cellular stage, is recited at a high level of generality and therefore encompasses well-known, conventional, and routine methods. Thus none of the steps of the rejected claims 1-17 and 19-20 amount to significantly more than the judicial exception.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(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) 1-15 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by WO 2019099955 (hereinafter “Ye”).
As to Applicant’s claims 1, Ye meets these limitations by disclosing the following.
Described are methods to isolate exosomes from a placenta or portion thereof, which is cultured in a bioreactor. Exosomes are secreted by the cells during the culture and the exosomes are secreted into the media, which facilitates further processing and isolation of the exosomes. Exosomes can be also isolated from the placenta or portion thereof at different stages of culture (e.g., at different time points and different perfusion liquids may be used at each recovery step). Once in the media, the exosomes can be further isolated using e.g., centrifugation, a commercially available exosome isolation kit, lectin affinity, and/or affinity chromatography (e.g., utilizing immobilized binding agents, such as binding agents attached to a substrate, which are specific for a small Rab family GTPase, annexin, flotillin, Alix, TsglOl, ESCRT complex, CD9, CD37, CD53, CD63, CD63A, CD81, CD82), Hsp70, Hsp90, epithelial cell adhesion molecules (EpCam), perforin, TRAIL, granzyme B, Fas, one or more cancer markers such as: Fas ligand, CD24, EpCAM, EDIL3, fibronectin, Survivin, PC A3, TMPRSS2:ERG, Glypican-l, TGF-b 1 , MAGE 3/6, EGFR, EGFRvIII, CD9, CD147, CA-125, EpCam, and/or CD24, or one or more inflammatory or pathogenic markers such as: a viral, fungal, or a bacterial protein or peptide including but not limited to a-synuclein, HIV or HCV proteins, tau, beta-amyloid, TGF-beta, TNF-alpha, fetuin-A, and/or CD133) . The isolated exosomes can be used for therapeutics, diagnostics, and as biotechnological tools. Para. 0120.
“Exosomes” as described are vesicles that are present in many and perhaps all eukaryotic fluids, including acscites fluid, blood, urine, serum and breast milk. They may also be referred to as extracellular vesicles. Exosomes are bi-lipid membrane vesicles secreted from living cells that play important functions in cell-cell communications. Exosomes are produced by cells, such a stem cells, epithelial cells and a sub-type of exosomes, defined as Matrix-bound nanovesicles (MB Vs), was reported to be present in extracellular matrix (ECM) bioscaffolds (non-fluid)… Exosomes can be released from the cell when multivesicular bodies fuse with the plasma membrane or released directly from the plasma membrane. Para. 0121.
Exosomes contain active biologies including lipids, cytokines, microRNA, mRNA and DNA. They may also function as mediators of intercellular communication via genetic material and/or protein transfer. Exosomes may also contain cell-type specific information that may reflect a cell’s functional or physiological state. Consequently, there is a growing interest in the development of clinical and biological applications for exosomes. Para. 0123.
Accordingly, exosomes isolated from human placenta or a portion thereof using the approaches described herein, optionally including characterization of said exosomes (e.g., by identifying the presence or absence of one or more proteins or markers on the exosomes) can be used to stimulate an immuno-modulation, an anti-fibrotic environment, and/or a pro-regenerative effect. Accordingly, exosomes isolated from human placenta or a portion thereof using the approaches described herein may be selected (e.g., according to markers present or absent on the exosomes), purified, frozen, lyophilized, packaged and/or distributed as a therapeutic product and/or a biotechnological tool.Para. 0124.
In some alternatives, it may be beneficial to identify exosomes having tumor markers or peptides, pathogenic markers or peptides, such as viral, fungal, or bacterial markers or peptides, and/or inflammatory markers, such as inflammatory peptides, so that such exosomes can be removed from a population of exosomes (e.g., removal by affinity chromatography with binding molecules such as, antibodies or binding portions thereof, which are specific for such tumor markers or peptides, pathogenic markers or peptides, and/or inflammatory markers or peptides). Accordingly, in some alternatives, for example, a first population of exosomes are isolated from human placenta or a portion thereof by the methods described herein and once the first population of exosomes is isolated this population of exosomes is further processed to remove one or more subpopulations of exosomes using a substrate having an immobilized antibody or binding portion thereof (e.g., a membrane, a resin, a bead, or a vessel having said immobilized antibody or binding portion thereof), wherein the immobilized antibody or binding portion thereof is specific for a marker or peptide present on the subpopulation of exosomes, which are selected for further isolation, such as, one or more tumor markers or peptides, pathogenic markers or peptides, e.g., viral, fungal, or bacterial markers or peptides, and/or inflammatory markers or inflammatory peptides. In some alternatives, a first population of exosomes isolated from human placenta or a portion thereof by the methods described herein are contacted with a substrate having an immobilized antibody or binding portion thereof (e.g., a membrane, a resin, a bead, or a vessel having said immobilized antibody or binding portion thereof), wherein the immobilized antibody or binding portion thereof is specific for one or more cancer markers such as: Fas ligand, CD24, EpCAM, EDIL3, fibronectin, Survivin, PC A3, TMPRSS2:ERG, Glypican-l, TGF-b I , MAGE 3/6, EGFR, EGFRvIII, CD9, CD147, CA-125, EpCam, and/or CD24 so as to isolate a second population of exosomes from the first population of exosomes based on the affinity to the immobilized antibody or binding portion thereof. In some alternatives, a first population of exosomes isolated from human placenta or a portion thereof by the methods described herein are contacted with a substrate having an immobilized antibody or binding portion thereof (e.g., a membrane, a resin, a bead, or a vessel having said immobilized antibody or binding portion thereof), wherein the immobilized antibody or binding portion thereof is specific for one or more inflammatory or pathogenic markers such as: a viral, fungal, or a bacterial protein or peptide including but not limited to a-synuclein, HIV or HCV proteins, tau, beta-amyloid, TGF-beta, TNF-alpha, fetuin-A, and/or CD133 or portions thereof so as to isolate a second population of exosomes from the first population of exosomes based on the affinity to the immobilized antibody or binding portion thereof.Para. 0125.
In some alternatives, the population of exosomes isolated and/or selected by the approaches described herein have markers or peptides that are useful for therapeutics such as perforin and/or granzyme B, which has been shown to mediate anti-tumor activity both in vitro and in vivo, or Fas, which has been found in exosomes that exert cytotoxic activity against target cancer cells. Accordingly, in some alternatives, a first population of exosomes isolated from human placenta or a portion thereof by the methods described herein are contacted with a substrate having an immobilized antibody or binding portion thereof (e.g., a membrane, a resin, a bead, or a vessel having said immobilized antibody or binding portion thereof), wherein the immobilized antibody or binding portion thereof is specific for perforin, TRAIL and/or granzyme B and/or Fas and a second population of exosomes from the first population of exosomes is isolated based on the affinity to the immobilized antibody or binding portion thereof to perforin, TRAIL and/or granzyme B and/or Fas. In some alternatives, a population of exosomes is isolated, which comprises CD63 RNAs, and/or a desired microRNA. In some alternatives, a population of exosomes is isolated and/or characterized after isolation using affinity chromatography or immunological techniques, wherein said population of exosomes comprise markers or peptides such as small Rab family GTPases, annexins, flotillin, Alix, TsglOl, ESCRT complex, CD9, CD37, CD53, CD63, CD63A, CD81, CD82), Hsp70, Hsp90) and/or epithelial cell adhesion molecules (EpCam). As detailed above, in some alternatives, a first population of exosomes isolated from human placenta or a portion thereof by the methods described herein are contacted with a substrate having an immobilized antibody or binding portion thereof (e.g., a membrane, a resin, a bead, or a vessel having said immobilized antibody or binding portion thereof), wherein the immobilized antibody or binding portion thereof is specific for small Rab family GTPases, annexins, flotillin, Alix, TsglOl, ESCRT complex, CD9, CD37, CD53, CD63, CD63A, CD81, CD82), Hsp70, Hsp90) and/or epithelial cell adhesion molecules (EpCam) and a second population of exosomes from the first population of exosomes is isolated based on the affinity to the immobilized antibody or binding portion thereof to small Rab family GTPases, annexins, flotillin, Alix, TsglOl, ESCRT complex, CD9, CD37, CD53, CD63, CD63A, CD81, CD82), Hsp70, Hsp90) and/or epithelial cell adhesion molecules (EpCam). In other alternatives, a population of exosomes isolated from human placenta or a portion thereof by the methods described herein are contacted with an antibody or binding portion thereof specific for one or more of small Rab family GTPases, annexins, flotillin, Alix, TsglOl, ESCRT complex, CD9, CD37, CD53, CD63, CD63A, CD81, CD82, Hsp70, Hsp90 and/or epithelial cell adhesion molecules (EpCam) and the binding of the antibody or binding portion thereof is detected with a secondary binding agent having a detectable reagent, which binds to said antibody or binding portion thereof (e.g., utilizing an ELISA or blotting procedure) so as to confirm the presence of the small Rab family GTPases, annexins, flotillin, Alix, TsglOl, ESCRT complex, CD9, CD37, CD53, CD63, CD63A, CD81, CD82), Hsp70, Hsp90 and/or epithelial cell adhesion molecules (EpCam) in the isolated exosome population. Para. 0126.
“Isolation” as described is a method for separating the exosomes from other materials. Isolation of exosomes may be performed by high centrifugal force in a centrifuge, utilization of commercially available kits, and the use of lectin affinity or affinity chromatography with binding agents (e.g., an antibody or binding portion thereof) specific for markers or peptides on the exosomes such as the markers or peptides mentioned above (e.g., binding agents specific for small Rab family GTPases, annexins, flotillin, Alix, TsglOl, ESCRT complex, CD9, CD37, CD53, CD63, CD63A, CD81, CD82), Hsp70, Hsp90, epithelial cell adhesion molecules (EpCam), perforin, TRAIL, granzyme B, Fas, one or more cancer markers such as: Fas ligand, CD24, EpCAM, EDIL3, fibronectin, Survivin, PC A3, TMPRSS2:ERG, Glypican-l, TGF-b I , MAGE 3/6, EGFR, EGFRvIII, CD9, CD147, CA-125, EpCam, and/or CD24, or one or more inflammatory or pathogenic markers such as: a viral, fungal, or a bacterial protein or peptide including but not limited to a-synuclein, HIV or HCV proteins, tau, beta-amyloid, TGF-beta, TNF-alpha, fetuin- A, and/or CD133). Para. 0127.
Thus as to Applicant’s claims 1-7, the Ye disclosures above meet Applicant’s claims 1-6, wherein the exosomes are equivalent to Applicant’s claimed extracellular vesicles (EVs). Isolating EV’s from tissue such as placenta (see isolation steps in paras. 0124-0127) is equivalent to Applicant’s claimed step of isolating from the sample a population of EV’s originating from a tissue. The next step of determining a biomarker from the isolated first population of EVs by contacting the first population of exosomes with a substrate, such as a bead, having immobilized antibody specific for inflammatory or pathogenic markers (see for example para. 0125), as taught by Ye, is equivalent to Applicant’s step of determining in said population of EVs a presence of at least one factor indicative of adverse cellular stage. Examiner notes that given the vagueness of claim 7, the Ye disclosure, discussed above, is interpreted to encompass claim 7.
As to claims 8 and 9, Ye discloses in paragraph 0125 that in some alternatives a first population of exosomes are isolated from human placenta or a portion thereof by the methods described and once the first population of exosomes is isolated this population of exosomes is further processed to remove one or more subpopulations of exosomes using a substrate having an immobilized antibody or binding portion thereof (e.g., a membrane, a resin, a bead, or a vessel having said immobilized antibody or binding portion thereof), wherein the immobilized antibody or binding portion thereof is specific for a marker or peptide present on the subpopulation of exosomes, which are selected for further isolation, such as, one or more tumor markers or peptides, pathogenic markers or peptides, e.g., viral, fungal, or bacterial markers or peptides, and/or inflammatory markers or inflammatory peptides. In some alternatives, a first population of exosomes isolated from human placenta or a portion thereof by the methods described herein are contacted with a substrate having an immobilized antibody or binding portion thereof (e.g., a membrane, a resin, a bead, or a vessel having said immobilized antibody or binding portion thereof), wherein the immobilized antibody or binding portion thereof is specific for one or more cancer markers such as: Fas ligand, CD24, EpCAM, EDIL3, fibronectin, Survivin, PC A3, TMPRSS2:ERG, Glypican-l, TGF-b I , MAGE 3/6, EGFR, EGFRvIII, CD9, CD147, CA-125, EpCam, and/or CD24 so as to isolate a second population of exosomes from the first population of exosomes based on the affinity to the immobilized antibody or binding portion thereof. In some alternatives, a first population of exosomes isolated from human placenta or a portion thereof by the methods described herein are contacted with a substrate having an immobilized antibody or binding portion thereof (e.g., a membrane, a resin, a bead, or a vessel having said immobilized antibody or binding portion thereof), wherein the immobilized antibody or binding portion thereof is specific for one or more inflammatory or pathogenic markers such as: a viral, fungal, or a bacterial protein or peptide including but not limited to a-synuclein, HIV or HCV proteins, tau, beta-amyloid, TGF-beta, TNF-alpha, fetuin-A, and/or CD133 or portions thereof so as to isolate a second population of exosomes from the first population of exosomes based on the affinity to the immobilized antibody or binding portion thereof. Para. 0125.
Thus Ye discloses isolating a first population of EVs’, and then isolating from this first population of EV’s a second population of EVs. The Ye step of isolating a first population (which can be via an immobilized antibody, see para. 0125 for example), is equivalent to the limitation in Applicant’s claim 8 (and therefore dependent claim 9) which recites “before (ii) isolating total EVs from said sample”. Also, Ye step of binding antibodies to the second population of EVs is equivalent to Applicant’s limitations in claim 8 (and therefore dependent claim 9) which recites “wherein said population of EVs is isolated from said total EV’s”.
As to claim 10, paragraph 0127 discloses that isolation may be by utilizing an antibody that binds to CD81.
As to claim 11, see paragraph 0120 ad 0125 which discloses that the markers are viral, fungal, bacterial or inflammatory markers.
As to claims 12-14, see for example paragraph 0126 of Ye. As to claim 14, given the vagueness of the claim, the RNA disclosed by Ye in paragraph 0126 is interpreted to meet claim 14.
As to claim 15, see paragraph 0125 of Ye.
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.
Claim(s) 16-17 and 19-21 is/are rejected under 35 U.S.C. 103 as being unpatentable over WO 2019099955 (hereinafter “Ye”).
Regarding claims 16-17 and 19-21, Ye, discussed above, is silent as the subject being a subject that is receiving treatment for the disease that is indicated by the determining step of claim 1.
However, Ye does disclose the following.
The isolated exosomes can be used for therapeutics, diagnostics, and as biotechnological tools. Para. 0120.
Exosomes isolated from human placenta or a portion thereof using the approaches described herein, optionally including characterization of said exosomes (e.g., by identifying the presence or absence of one or more proteins or markers on the exosomes) can be used to stimulate an immuno-modulation, an anti-fibrotic environment, and/or a pro-regenerative effect. Accordingly, exosomes isolated from human placenta or a portion thereof using the approaches described herein may be selected (e.g., according to markers present or absent on the exosomes), purified, frozen, lyophilized, packaged and/or distributed as a therapeutic product and/or a biotechnological tool.Para. 0124.
In some alternatives, the population of exosomes isolated and/or selected by the approaches described herein have markers or peptides that are useful for therapeutics. Para. 0126.
Thus, regarding Applicant’s claim 16, Ye teaches that exosomes isolated by the disclosed methods can be used for therapy. It would have been obvious to one skilled in the art that the exosomes isolated by the Ye method can be used for therapy, including for therapy of the patient subject who is already receiving therapy. Moreover, in utilizing the Ye method of determining the population of EVs that bind to the capturing antibody to determine responsiveness of the subject to the treatment is a prima facie case of obviousness as it appears to result in a predictable outcome given the knowledge in the art regarding exosomes as being useful for diagnostics and therapeutic (see for example para. 0120, 0124, 0126).
Regarding claim 17, given that “early” is vague and indefinite (as discussed further above), the disclosures of Ye (see discussion of claim 1) encompasses a method of early detection f a disease or of a disease symptom (see for example para. 0125 of Ye).
As to claim 19, see discussion of claims 1 and 16 above, which encompasses claim 18. Also, it would have been obvious to one skilled in the art that a decrease in adverse cellular state indicates responsiveness to the treatment.
As to claims 20-21, as mentioned above (see discussion of claim 16), Ye teaches that exosomes isolated by the disclosed methods can be used for therapy. It would have been obvious to one skilled in the art that the patient subject be treated, such as with exosomes as suggested by Ye, as needed, before and/or after the method of detecting adverse cellular state (i.e., the method discussed above regarding claim 1).
Conclusion
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/Ann Montgomery/ Primary Examiner, Art Unit 1678