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 Objections
Claims 2 is objected to because of the following informalities: “diagnosis” in line 1 should be –diagnosing--. Appropriate correction is required.
Claim Rejections - 35 USC § 112
Claims 2-17 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.
Claim 2 recites a method for diagnosing colorectal cancer, comprising, among other things, “assaying the supermeres for colorectal cancer biomarker”. However, the claim does not recite a step for diagnosing colorectal cancer [nor how it is done], and thus the claim is vague and indefinite.
Claim 3 is rejected since it depends from claim 2 without clarifying the above issue.
Claim 4 is rejected since it recites “wherein the colorectal cancer biomarker comprises an elevated level of …TGFBI, etc.” However, a level of TGFBI, etc. is not a biomarker. Also, it is not clear as to what it is elevated from. Thus the claim remains vague.
Claim 5 (and thus claim 6) are rejected since it recites a “method for prognosing colorectal cancer” but the claim is not clear as to what is the step of prognosing.
Claim 7 (and thus claims 8-10) recite a “method for diagnosing a proteinopathy” but does not recite a step of diagnosing. Thus the claim remains vague as to how the diagnosis is performed.
Claim 11 recites a “method for treating SARS-CoV-2” but does not clearly indicate what step treats SARS-CoV-2. Thus the claim remains vague as to how the treating is performed.
Claim 12 recites a “method for modulating the Renin-Angiotensin Aldosterone System”, but does not clearly indicate a step for modulating the Renin-Angiotensin Aldosterone System. Thus the claim is vague as to how the modulating step is performed. Also, “an effective amount of the supermeres” is vague and indefinite since it does not indicate for what it is effective.
Claim 13 recites “a method for delivering an agent to the nervous system” but does not clearly indicate a step for delivering an agent to the nervous system. Thus the claim is vague as to what agent is delivered to the nervous system. Also “an effective amount of the supermeres” is vague and indefinite since it does not indicate for what it is effective [no disease or condition is even mentioned in the claim].
Claim 14 (and thus claim 15) recite a “method for treating a neurodegenerative” disease but does not clearly indicate a step for treating a neurodegenerative disease. Thus the claim is vague as to how the treating step is performed. Also, “an effective amount of supermeres” is vague and indefinite since it does not indicate for what it is effective.
Claim 16 recites a “method for treating a corneal dystrophy” but does not clearly indicate a step for treating corneal dystrophy. Thus the claim is vague as to how corneal dystrophy is treated. Also, “an effective amount of supermeres” is vague and indefinite since it does not indicate for what it is effective.
Claim 17 recites a “method for monitoring exposure to environmental toxins” but does not clearly indicate a step for monitoring exposure to environmental toxins”. Examiner notes that “assaying the supermeres for an environmental toxin exposure disease biomarker” does not sufficiently clarify what the monitoring step comprise. Thus the claim is vague as to how exposure to environmental toxins is monitored.
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.
WRITTEN DESCRIPTION
Claims 2-17 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 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.
These claims recite limitations (see in details below) that are not described in the specification in such a way as to show that Applicant has possession of the claimed invention at the time the application was filed, as will be discussed further below for each group of limitations.
CLAIMS 2-6:
Claims 2-6 recites a method for diagnosing colorectal cancer. Claim 4 recites several biomarkers. However, there is no disclosure in Applicant’s specification that support that Applicant had possession of the claimed invention at the time the application was filed.
For instance, claim 4 recites GPI. Paragraph 0052 of Applicant’s specification (from PreGrant Publication US 20250123297) mentions GPI, and is provided below.
“The most abundant protein in highly purified DiFi exosomes was the glycophosphatidylinositol (GPI)-linked dipeptidase DPEP1 that has been linked to CRC metastasis (Park, S. Y., et al. Oncotarget 2016 7:9501-9512). Diffuse overexpression of DPEP1 in a clinically well-annotated CRC tissue microarray portends a worse outcome, and DPEP1 is increased in sEVs isolated from the plasma of CRC patients compared to normal individuals. Moreover, a subpopulation of exosomes released from DiFi cells is highly enriched in DPEP1, two circulating biomarkers for CRC (CEA and EPCAM), and the ectonucleotidase CD73 that is involved in immunosuppression and is overexpressed in CRC (Goswami, S., et al. Nat Med 2020 26:39-46; Hammami, A., et al. Semin Immunol 2019 42:101304).” Para. 0052 (emphasis added).
While Applicant cites a reference in paragraph 0052 to show that glycophosphatidylinositol (GPI)-linked dipeptidase DPEP1 has been linked to CRC metastasis, there is no indication that GPI in supermeres provide a diagnosis of colorectal cancer [CRC].
There is no showing of what form of GPI in supermeres are found and/or in what quantity such that they are diagnostic of colorectal cancer.
Applicant’s paragraph 0004
“Disclosed herein is a newly identified secreted nanoparticle that is morphologically and molecularly distinct from the recently described nanoparticle termed an exomere. The disclosed nanoparticle is referred to herein as a supermere. Both exomeres and supermeres are amembranous in contrast to membrane-enclosed extracellular vesicles (EVs). Supermeres are smaller and morphologically distinct from exomeres. These supermeres contain cargo that contribute to the pathogenesis of colorectal cancer (CRC) and may be potential biomarkers for CRC as some of these cargo have been detected in the circulation of cancer patients. In addition, supermeres from cetuximab-resistant CRC cells are able to confer resistance when added to cetuximab-sensitive CRC cells. Moreover, the receptor for SARS-CoV-2, angiotensin-converting enzyme 2 (ACE2), is present in large amounts in supermeres isolated from conditioned medium of DiFi cells, a human CRC cell line. The isoforms detected in these supermeres are smaller than the full-length band detected in DiFi whole cell lysates and in small EVs; this smaller form corresponds to the ectodomain of ACE2. Moreover, ACE2 is α2,6-sialylated in DiFi cells, small EVs, exomeres and supermeres. A processed form of amyloid precursor protein (APP), a protein that is associated with the pathogenesis of Alzheimer's disease, was also detected in supermeres, as well as the receptor tyrosine kinase MET and glypican-1 (GPC1).” Para. 0004.
Applicant’s disclosure, such as in paragraph 0004, show that biomolecules in supermeres may be a different form of the biomolecule found elsewhere. Moreover, nowhere in Applicant’s specification is there support for a particular biomarker found in supermeres that can be used for diagnosing colorectal cancer.
For instance, Claim 4 also recites the biomarker TGFBI and ENO1, which is disclosed for example in paragraph 0080. However, paragraph 0080 does not show support that TGFBI in supermeres are diagnostic of colorectal cancer. There is no showing of what form of TGFBI in supermeres are found and/or in what quantity such that they are diagnostic of colorectal cancer.
Applicant’s paragraph 0080 is shown below.
“Based on these findings, it is proposed that TGFBI, ENO1 and GPC1 may be useful markers for extracellular nanoparticles (exomeres and supermeres), while HSPA13 and ENO2 are more specifically associated with supermeres. Full-length CD73 may be a useful general marker for sEVs. Supermeres contain a number of clinically relevant biomolecules, such as PCSK9, ACE, ACE2, MET, GPC1 and APP, and supermeres are efficiently taken up in many organs compared to sEVs and exomeres, including the heart and brain. Some fruitful areas of future investigation will be determining the biogeneis of supermeres and exomeres and exploring the physiological and pathophysiological consequences of these nanoparticles and their cargo.” Para. 0080 (emphasis added).
While various biomolecules are mentioned in paragraph 0080, there is no disclosure regarding TGFBI in supermeres being diagnostic of colorectal cancer. There is no showing of what form of TGFBI in supermeres are found and/or in what quantity such that they are diagnostic of colorectal cancer.
Rather, paragraph 0080 states that the disclosed biomolecules “may be useful markers for extracellular nanoparticles (exomeres and supermeres),” and that “[s]upermeres contain a number of clinically relevant biomolecules, such as PCSK9, ACE, ACE2, MET, GPC1 and APP” and suggests “future investigation”.
Thus, at best, the specification suggest that these potential agents must first be screened in an assay to ascertain if the agents have the functions required by the instant claims. Applicant may have presented the public with an idea of how to perform an assay that might identify some biomolecules in supermeres that fall within the scope of the claim, which of course, may well identify none.
Claim also recites the biomarker ENO2, LDHA7B, ALDOA, ACTN4,, SCTD and miR-R-1246. Nowhere is there disclosure in Applicant’s specification that these biomolecules in supermeres are used for colorectal cancer biomarker. Some biomarkers are found only in claim 4 and have no support elsewhere in the claims.
Also, regarding claims 2 and 3, which is generic to claim 4,
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 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).
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.” 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).
Applicant’s paragraph 0014 discloses the following which mentions colorectal cancer but which does not support any particular biomolecules in supermeres being diagnostic of colorectal cancer, and therefore cannot support a generic claim of isolating supermeres and assaying the supermeres for colorectal cancer biomarker (as claimed in Applicant’s claims 2 and 3).
“FIG. 5H shows immunoblot of select proteins in the sEV-P, exomeres and supermeres derived from Calu-3−, LIM1215−, DiFi 1342 cells, and a colorectal cancer (CRC) patient plasma sample. Thirty micrograms of protein from each fraction were analyzed. WCL, whole cell lysate; exom, exomere; super, supermere.” Para. 0014 (emphasis added).
“FIG. 6A to 6L shows supermeres exhibit distinct proteomic profiles and the supermere protein TGFBI is a potential CRC biomarker. FIG. 6A is a Venn diagram of unique and common proteins identified in DiFi-derived sEVs, NV, exomeres and supermeres. FIG. 6B shows principal component analysis of normalized DiFi proteomic mass spectral counts. FIG. 6C is a heatmap of top 20 most abundant proteins in all samples from DiFi. FIG. 6D is a heatmap of top 20 most abundant proteins in supermeres derived from DiFi, PANC-1 and MDA-MB-231 cells. FIG. 6E is a Venn diagram of unique and common top 50 most abundant proteins identified in supermeres derived from DiFi, PANC-1 and MDA-MB-231 cells. FIG. 6F is an immunoblot of representative proteins in DiFi, PANC-1 and MDA-MB-231-derived supermeres. Thirty micrograms of protein from each fraction were analyzed. FIG. 6G shows FAVS analysis of TGFBI level in the sEV-P, exomeres and supermeres derived from DiFi cells. FIG. 6H shows immunohistochemical staining of TGFBI expression in normal (NL) colon and colorectal cancer (CRC) tissue samples. Representative images are shown. Scale bar, 100 μm. FIGS. 6I and 6J shows overall survival (FIG. 6I) and progression-free survival (FIG. 6J) analysis of CRC patients comparing TGFBI level (high vs. low) using Kaplan and Meier method with data compared among marker groups using the log-rank test. FIG. 6K shows ELISA analysis of TGFBI levels in supermeres derived from normal or CRC patient plasma. FIG. 6L shows FAVS analysis of TGFBI level in sEV-P, exomeres and supermeres derived from CRC patient plasma.” Para. 0015.
However, nowhere in Applicant’s specification is there a disclosure of using any particular biomolecule in supermere to diagnosis colorectal cancer, nor how it can be done (such as detecting an increase or decrease, or a certain threshold amount of a particular biomolecule.)
Similarly, regarding claims 5 and 6, there is no support in Applicant’s specification for assaying supermeres for the prognosing colorectal cancer, or assaying supermeres for the ability to confer drug resistance to a colorectal cancer cell in vitro.
For example, Applicant discloses the following in paragraphs 0004 and 0061, which mentions APP and Alzheimer’s disease, but which does not provide support for prognosing colorectal cancer.
“As there was a greater brain uptake of supermeres compared to both sEVs and exomeres (FIG. 5G), it was decided to examine APP as C-terminal fragments of this protein have previously been observed in exosomes (Miranda, A. M., et al. Nat Commun 2018 9:291). APP, a cell surface transmembrane precursor protein, is sequentially cleaved by α-, β- and γ-secretases to generate soluble APPs, C-terminal fragments and amyloid beta, which are essential to the pathogenesis of Alzheimer's disease (Barao, S., et al. Trends Neurosci 2016 39:158-169). APP and other membrane proteins associated with APP or Alzheimer's disease, including APLP2, underwent ectodomain shedding and were highly enriched in supermeres (FIG. 8A). The enrichment of ectodomain APP in exomeres and supermeres derived from both DiFi and SC cells, and the confinement of full-length APP to cells and sEVs, was confirmed by immunoblotting with antibodies specific to ectodomain (N-terminal) or cytoplasmic (C-terminal) epitopes (FIG. 8B, 15A). Enrichment of APP in supermeres was further confirmed by FAVS analysis (FIG. 8C).” Para. 0061 (emphasis added).
CLAIMS 7-10:
Similarly, claims 7-11 also do not have support in the specification for assaying supermeres for a proteinopathy disease biomarker [e.g., Alzheimer’s disease]. Thus, the inventions of claims 7-11 are not described in the specification in such a way as to show that Applicant has possession of the claimed invention at the time the application was filed.
For example, paragraph 0004 discloses the following.
“…The isoforms detected in these supermeres are smaller than the full-length band detected in DiFi whole cell lysates and in small EVs; this smaller form corresponds to the ectodomain of ACE2. Moreover, ACE2 is α2,6-sialylated in DiFi cells, small EVs, exomeres and supermeres. A processed form of amyloid precursor protein (APP), a protein that is associated with the pathogenesis of Alzheimer's disease, was also detected in supermeres, as well as the receptor tyrosine kinase MET and glypican-1 (GPC1).” Para. 0004.
“As there was a greater brain uptake of supermeres compared to both sEVs and exomeres (FIG. 5G), it was decided to examine APP as C-terminal fragments of this protein have previously been observed in exosomes (Miranda, A. M., et al. Nat Commun 2018 9:291). APP, a cell surface transmembrane precursor protein, is sequentially cleaved by α-, β- and γ-secretases to generate soluble APPs, C-terminal fragments and amyloid beta, which are essential to the pathogenesis of Alzheimer's disease (Barao, S., et al. Trends Neurosci 2016 39:158-169). APP and other membrane proteins associated with APP or Alzheimer's disease, including APLP2, underwent ectodomain shedding and were highly enriched in supermeres (FIG. 8A). The enrichment of ectodomain APP in exomeres and supermeres derived from both DiFi and SC cells, and the confinement of full-length APP to cells and sEVs, was confirmed by immunoblotting with antibodies specific to ectodomain (N-terminal) or cytoplasmic (C-terminal) epitopes (FIG. 8B, 15A). Enrichment of APP in supermeres was further confirmed by FAVS analysis (FIG. 8C).” Para. 0061 (emphasis added).
There is no disclosure in paragraphs 0004, 0061, nor anywhere else in Applicant’s disclosure that support assaying supermeres for a proteinopathy disease biomarker [e.g., Alzheimer’s disease]. Thus, the inventions of claims 7-11 are not described in the specification in such a way as to show that Applicant has possession of the claimed invention at the time the application was filed.
CLAIM 11 and CLAIM 12:
Similarly, claim 11 also does not have support in the specification for treating SARS-CoV-2 by isolating polypeptides from supermeres comprising ectodomain of ACE2 and administering the polypeptides to the subject in an amount sufficient to bind SARS-CoV-2 in the subject systemically and/or in an aerosolized form.
Claim 12 also does not have support in the specification for modulating Renin-Angiotensin Aldosterone System.
Thus, the inventions of claims 11 and 12 are not described in the specification in such a way as to show that Applicant has possession of the claimed invention at the time the application was filed.
For example, paragraph 0006 of the specification discloses the following which mentions administering ectodomain of ACE2 and SARS-CoV-2 and Renin-Angiotensin Aldosterone System, but it does not provide support to show that Applicant had possession of the claimed invention at the time the application was filed. Rather, paragraph 0006 merely suggests such potential. But no studies were performed, and there is no other evidence that Applicant had possession of the claimed invention. A suggestion to perform an assay that might identify some biomolecules in supermeres that fall within the scope of the claim does not support that Applicant had possession of the claimed invention at the time the application was filed, and such assay, of course, may well identify none.
Paragraph 0006 discloses the following.
“Supermeres contain a large fragment of the ectodomain of ACE2. As disclosed herein, this form of ACE2 may bind SARS-CoV-2 and reduce the severity of infection, as has been shown for soluble ACE2. ACE2 is downregulated during viral infection, most notably with coronavirus infection (SARS and COVID-19), and this process can drive proteins towards secretion. In addition, ACE2 present in the circulation may be relevant to disorders of Renin-Angiotensin Aldosterone System (RAS/RAAS) that is associated with cardiovascular disease and cardiovascular problems associated with viral infection. Therefore, ACE2 in supermeres may provide diagnostic information. By delivering ACE2 in different forms in supermeres to patients systemically and/or in an aerosolized form might provide a specific treatment for patients. In addition, disclosed herein is a strategy of delivering this form of ACE2 in nanoparticles systemically and in an aerosolized form into the lungs.” Para. 0006 (emphasis added).
CLAIMS 13-15:
Likewise, claims 13 and 14 do not have support in the specification for administering an effective amount of supermeres (claim 13), nor for isolating supermeres comprising HNRNPA2B1 and aministering an effective amount of the supermere to the subject, [for treating neurodegenerative disease] (claim 14), nor specifically for Alzheimer’s disease (claim 15).
For example, paragraph 0067 only discloses the following regarding HNRNPA2B1. “…However, hnRNPA2B1 was only detected in DiFi cells and supermeres (FIG. 9I), suggesting the possible involvement of hnRNPA2B1 in miRNA sorting can be attributed to supermeres.”
Also, paragraph 0005 mentions neuordegenerative disease but discloses only the potential of supermeres as serving as biomarker.
“Supermeres can be obtained relatively quickly and in large amounts from conditioned medium and plasma. They contain a number of cargo that may serve as biomarkers for a number of disease states, including cancer, heart disease, and neurodegenerative disorders, amongst others. Because these are new secreted components of biofluids, they have not thus far been associated with disease states.” Para. 0005 (emphasis added).
Paragraph 0005 does not provide support to show that Applicant had possession of the claimed invention at the time the application was filed. Rather, paragraph 0005 merely suggests such potential. But no studies were performed, and there is no other evidence that Applicant had possession of the claimed invention. A suggestion to perform an assay that might identify some biomolecules in supermeres that fall within the scope of the claim does not support that Applicant had possession of the claimed invention at the time the application was filed, and such assay, of course, may well identify none.
Paragrpahs 0004 and 0061 mentions Alzheimer’s disease, but as mentioned further above, does not support assaying supermeres for Alzheimer’s disease or other diseases recited in claim 15. Thus, the inventions of claims 7-11 are not described in the specification in such a way as to show that Applicant has possession of the claimed invention at the time the application was filed.
CLAIMS 16 AND 17:
Claim 16 recites a method for treating a corneal dystrophy, comprsing isolating supermeres comprising TGFBI, and administering an effective amount of the supermeres to the subject.
Claim 17 recites a method for monitoring exposure to environmental toxins in a subject comprising isolating supermeres, and assaying the supermeres for an environmental toxin exposure disease biomarker.
However, nowhere in the specification is there a mentioning of “corneal dystrophy” except in claim 16.
Also, nowehere in the specification is there a mentioning of “environmental toxin” except in claim 17. Also, nowhere in the specification (including claim 17) is there a disclosure of a particular “environmental toxin exposure disease biomarker”. Thus there is no example of such a biomarker in the specification.
There is no support for performing the methods of claims 16 or 17. Thus, the inventions of claims 16 and 17 are not described in the specification in such a way as to show that Applicant has possession of the claimed invention at the time the application was filed.
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.
ENABLEMENT
Claims 2-17 are rejected under 35 U.S.C. 112, first paragraph, because the specification does not reasonably provide enablement for the claimed inventions. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
Enablement requires that the specification teach those in the art to make and use the invention without undue experimentation. Factors to be considered in determining whether a disclosure would require undue experimentation include (1) the nature of the invention, (2) the state of the prior art, (3) the predictability or lack thereof in the art, (4) the amount of direction or guidance present, (5) the presence or absence of working examples, (6) the quantity of experimentation necessary, (7) the relative skill of those in the art, and (8) the breadth of the claims.
The nature of the invention –
Applicant’s claims are directed to different inventions as follows.
CLAIMS 2-6:
Claims 2-6 recites a method for diagnosing colorectal cancer. Claim 4 recites several biomarkers.
CLAIMS 7-10:
Claims 7-11 recites assaying supermeres for a proteinopathy disease biomarker [including Alzheimer’s disease].
CLAIM 11 and CLAIM 12:
Claim 11 recites treating SARS-CoV-2 by isolating polypeptides from supermeres comprising ectodomain of ACE2 and administering the polypeptides to the subject in an amount sufficient to bind SARS-CoV-2 in the subject systemically and/or in an aerosolized form.
Claim 12 recites modulating Renin-Angiotensin Aldosterone System.
CLAIMS 13-15:
Claims 13 recites a method comprising administering an effective amount of supermeres.
Claim 14 recites a method comprising isolating supermeres comprising HNRNPA2B1 and aministering an effective amount of the supermere to the subject, [for treating neurodegenerative disease].
Claim 15 recites a method for treating Alzheimer’s disease.
CLAIMS 16 AND 17:
Claim 16 recites a method for treating a corneal dystrophy, comprsing isolating supermeres comprising TGFBI, and administering an effective amount of the supermeres to the subject.
Claim 17 recites a method for monitoring exposure to environmental toxins in a subject comprising isolating supermeres, and assaying the supermeres for an environmental toxin exposure disease biomarker.
The predictability or lack thereof of in the art –
It is not predictable that the presence or amount of a biomolecule in supermeres will diagnose or treat the particular diseases as recited in the claims, as biochemistry is complex and unpredictable.
The amount of direction or guidance present –
There is a lack of direction or guidance in the art as well as in Applicants’ own specification regarding these diagnoses or treatment. Applicant’s disclosures provide no studies nor information as how the diagnoses or treatment are made (for example, what quantity of what biomarkers in what sample indicates a diagnosis of what disease, or what amount of what agent will treat what disease). See discussion above regarding the written description rejection, which is also relevant to a lack of enablement and will not be repeated here for purposes of brevity.
The presence or absence of working examples –
There is no working example in the specification for the recited diagnoses or treatments.
The quantity of experimentation necessary –
It would be undue experimentation for a skilled artisan to make and use the inventions as claimed since there is no guidance as to the correlation between the presence or amount of any biomolecule in supermeres and a disease. Examiner notes that a correlation of a biomarker in exosomes and a disease [known in the prior art as disclosed by Applicant’s specification, see discussion above under “written description” rejection] is insufficient to support a correlation between the biomarker in supermeres and the disease. As noted above in the written description rejection, the biomarker may be in a different form in supermeres than in exosomes, and in any case, it is not predictable that its presence in supermeres is diagnostic of a disease just because it is known in the art to be diagnostic of a disease when found in exosomes. For example, in what amount would that biomarker in supermeres be indicative of the disease? Applicant and/or the prior art may suggest that a biomolecule (or some form of it) is diagnostic or therapeutic for a particular disease, but undue experimentation would be required to know whether it really is diagnostic or therapeutic for the disease and in what amount.
The relative skill of those in the art –
The level of skill in the art is high given that biochemistry, diagnostic art, and the medical field is complex.
The breadth of the claims –
Some claims recite particular biomarkers (see discussion under “written description” above) and some claims are generic in reciting isolation of supermeres and diagnosing a disease or administering the supermeres to treat the particular disease. As discussed above, there is no support in the disclosure for these claimed inventions, whether for the particular biomolecules recited or for the generic invention (that recite supermeres in general, without reciting a particular biomolecule).
In summary, there is a lack of disclosure in the prior art as well as in Applicants’ own specification to enable one skilled in the art to make and use Applicant’s claimed inventions. Thus, the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with claim 10.
Allowable Subject Matter
Claim 1 is allowed.
The following is a statement of reasons for the indication of allowable subject matter: while exomeres and their isolation are known in the prior art, the prior art does not teach or suggest ultracentrifuging a supernatant at 100,000 to 167,000 x g for 16 to 18 hours to produce a pellet that comprises exomeres and a second supernatant from above the exomere pellet that contains supermeres (step f), and ultracentrifuging this supernatant at 300,000 to 400,000 x g for 16 to 18 hours to produce a third pellet that comprises supermeres (step g).
Conclusion
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/Ann Montgomery/Primary Examiner, Art Unit 1678
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