DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim status
In the paper filed 17 January 2023, claims 1-34 have been cancelled and new claims 35-54 were added. Therefore, claims 35-54 are pending.
Claims 35-54 are herein under examination.
Priority
This application was filed 01/17/2023 and is a 371 application of PCT/IL2021/050885 filed on 07/20/2021, which claims benefit to Priority from Provisional Application 63133350, filed 01/03/2021 and 63053780, filed 07/20/2020. Thus, the earliest possible priority for the instant application is 07/20/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/23/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Abstract Objection
The abstract of the disclosure filed 01/17/2023 is objected to because the abstract is only 41 words in length, and it is not submitted as a single paragraph on a separate sheet as required. Therefore, submitted abstract is considered non-compliant. Applicant is reminded of the proper language and format for an abstract of the disclosure. MPEP §608.01(b) states that the abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided. Therefore, appropriate correction is required.
Claim Objections
Claims 35 and 53-54 are objected to because of the following informalities: abbreviations such as EVs, LIP, AREG, HGF and TSG6 should be spelled out in full at the first encounter in the claims. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 45, 51-52 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 45 contains the trademark/trade name Plasma-Lyte A and CryoStor. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or pre-AIA 35 U.S.C. 112, second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade names Plasma-Lyte A and CryoStor are used as excipient and, accordingly, the identification is indefinite.
Claims 51-52 are directed to “compared to corresponding EXO-MSCs,” however, POSITA would not be reasonably interpreted the metes and bounds of the corresponding. Claim 35 discloses a combination of MSC-NTFs and EXO-MSC-NTFs. Claim 51 and 52 do not appear to show any correspondence between two of these distinct cells. The rejection may be obviated by amending the claims 51-52 to recite “wherein said EXO-MSC-NTFs when compared to EXO-MSC.”
Claims 51 recites the limitation “EXO-MSC”. There is insufficient antecedent basis for this limitation in the claim. See MPEP 2173.05(e)
Furthermore, claims 51-52 recited substantially less and substantially more. These terms are not defined by the claim, and the specification does not provide a standard for ascertaining the requisite degree “substantially”, and POSITA would not be reasonably apprised of the scope of the invention. Claim scope cannot depend solely on the unrestrained, subjective opinion of a particular individual purported to be practicing the invention. Therefore, these terms render the claims indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Appropriate correction is required.
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 35-40, 44-45, and 47-54 are rejected under 35 U.S.C. 103 as being unpatentable over Simonson et al., (US20160199413A1, published on Jul 14, 2016; cited in PTO892; hereinafter “Simonson”), in view of Witwer et al (Journal of extracellular vesicles, 2019, 8(1), p.1609206; cited in PTO892; hereinafter “Witwer”) and further in view of Errichelli et al. (WO2019092145; Pub. Date: 16 May 2019; cited in PTO892; hereinafter “Errichelli”).
With respect to claims 35, 37-39, and 48-49, Simonson teaches a method for treating a lung condition notably acute respiratory distress syndrome (ARDS) in a patient in need (abstract, [0006], [0085]), comprising administering to the patient a therapeutically effective of a pharmaceutical composition comprising clinically potent MSCs and extracellular components (primarily extracellular vesicles such as exosomes) [0006], [0097]. Simonson further discloses that the Extracellular vesicles and other paracrine factors (i.e., neurotrophic factors) are of great importance for the therapeutic efficacy of MSCs. MSCs and the vesicle population are positive for neurotrophic factors (claim 1(b),(g), [0064] [0069], [0076]). Therefore, prima facie obviousness of the combination of active agent MSC-NTFs and EXO-MSC-NTFs has been established by Simonson.
Claim 35 is recited a plurality of small EVs (sEVs). In the interest of compact prosecution, the Examiner interprets sEVs are membrane-bound vesicles with a size of less than 200 nm (see SPEC [000114]).
However, regarding claim 35, Simonson is silent to EVs size of less than 200 nm. However, such was known in the prior art.
Witwer teaches a method to preparation of small extracellular vesicles (sEVs) consisting of smaller than 200 nm in diameter from mesenchymal stem cells (MSCs) for transiting rapidly towards therapeutic application (abstract, p. 4 right col. 2nd ¶ of Witwer).
MPEP 2143 (A) states that combining prior art elements according to known methods to yield predictable results. The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395. Accordingly, it would have been obvious to practice a method for treating a lung condition of Simonson and combine the sEVs as taught by Witwer with a reasonable expectation of success. The POSITA would have been motivated at the time of filing to do so as taught by Witwer because MSC-sEVs cargo molecule promote the clinical and therapeutic application (p. 9 left-Col. 2-3rd ¶). The POSITA would have had a reasonable expectation of success in combining the teachings of Simonson and Witwer because each of these teachings both successfully generated MSC-sEVs. Therefore, the products and method as taught by Simonson et al. in view of Errichelli et al. would have been prima facie obvious over the method of the instant application.
With respect to claim 36, Simonson teaches that the lung condition comprises a viral lung infection or a non-viral lung infection [0100], [0128-0129].
However, regarding claim 40, Simonson is silent to pharmaceutical composition comprises about 109 to about 1013 EXO-MSC-NTFs. However, such was known in the prior art.
With respect to claim 40, Errichelli teaches an extracellular vesicle (EV or exosome) therapeutics derives from MSCs (p. 29 of Errichelli), wherein the EVs comprise polypeptides therapeutics, wherein the therapeutic polypeptide is neurotrophic factors (abstract, claim 7 of Errichelli). Errichelli further discloses that the pharmaceutical composition comprising dosages of EVs when applied in vivo may naturally vary considerably depending on the disease to be treated. Therefore, EVs may be present in concentrations of 108 to 1014 particles/unit Vol (for instance per ml) (p. 9 of Errichelli).
MPEP 2143 (A) states that combining prior art elements according to known methods to yield predictable results. The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395. Accordingly, it would have been obvious to practice a method for treating a lung condition of Simonson and combine the EXO-MSC-NTFs as taught by Errichelli with a reasonable expectation of success. The POSITA would have been motivated at the time of filing to do so as taught by Errichelli because encoded EV cargo molecule includes NTF (p. 20 3rd ¶) will allowing the release of NTF in a target location (p. 16 1st ¶). The POSITA would have had a reasonable expectation of success in combining the teachings of Simonson and Errichelli because each of these teachings both successfully generated EXO-MSC-NTFs. Therefore, the products and method as taught by Simonson et al. in view of Errichelli et al. would have been prima facie obvious over the method of the instant application.
With respect to claims 44-45, Simonson teaches that the pharmaceutical composition further comprises an excipient DMEM [0010], [0086-0087], [0121].
With respect to claim 47, Simonson teaches that the administration of the pharmaceutical composition comprises systemic administration [0130] or intravenous administration (claim 17, [0040], [0081], [0110].
With respect to claim 50, Simonson teaches that the viral lung infection is influenza [0129].
With respect to claims 51-54, the characteristics of the claimed pharmaceutical composition comprising combination of MSC-NTFs and EXOMSC-NTFs have the same structure as the product of Simonson et al. and the claimed properties or functions are presumed to be inherent. Therefore, it would necessarily have the same characteristics. MPEP 2112.01(I) and (II) states that “when the structure taught by the reference is identical or substantially identical to that of the claims, the claimed properties or functions are presumed to be inherent”. Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). MPEP 2112 (II) also states that for composition of matter claims, if the composition is physically the same, it must have the same properties.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claims 35-43 are rejected under 35 U.S.C. 103 as being unpatentable over Simonson et al., (US20160199413A1, published on Jul 14, 2016; cited in PTO892; hereinafter “Simonson”), in view of Witwer et al (Journal of extracellular vesicles, 2019, 8(1), p.1609206; cited in PTO892; hereinafter “Witwer”) and Errichelli et al. (WO2019092145; Pub. Date: 16 May 2019; cited in PTO892; hereinafter “Errichelli”) as applied to claims 35-40 above, and further in view of and Mitsialis et al., (US20140065240A1, Pub. Date: Mar. 6, 2014; cited in PTO892; hereinafter “Mitsialis”),
As stated above regarding claim 35, Simonson teaches a method for treating a lung condition notably acute respiratory distress syndrome (ARDS) in a patient in need (abstract, [0006], [0085]), comprising administering to the patient a therapeutically effective of a pharmaceutical composition comprising clinically potent MSCs and extracellular components (primarily extracellular vesicles such as exosomes) [0006], [0097]. Simonson further discloses that the Extracellular vesicles and other paracrine factors (i.e., neurotrophic factors) are of great importance for the therapeutic efficacy of MSCs. MSCs and the vesicle population are positive for neurotrophic factors (claim 1(b),(g), [0064] [0069], [0076]). Therefore, prima facie obviousness of the combination of active agent MSC-NTFs and EXO-MSC-NTFs has been established by Simonson.
However, regarding claim 41, Simonson is silent to therapeutically effective regime comprises repeated administration of the active agent on different days. However, such was known in the prior art.
With respect to claims 41-43, Mitsialis teaches compositions comprising mesenchymal stem cell (MSC) derived exosomes, and methods of their use in subjects having certain lung diseases including acute respiratory distress syndrome (ARDS) (abstract [0004]-[0015] of Mitsialis). MSC exosomes are repeated administered (e.g., day 1, day 3 and day 5) in pharmaceutically acceptable compositions [0085] comprises administration on at least five different days [0082].
MPEP 2143 (A) states that combining prior art elements according to known methods to yield predictable results. The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395. Accordingly, it would have been obvious to practice a method for treating a lung condition of Simonson and combine the administration dose as taught by Mitsialis with a reasonable expectation of success. The POSITA would have been motivated at the time of filing to do so as taught by Mitsialis because maximal activity could achieve when the MSC exosomes were administered repeatedly every 2-4 days [0084]. Furthermore, Mitsialis discloses that depending on the severity of the disease, the health of the subject, and the route of administration, inter alia, the single or repeated administration of low or high dose MSC exosomes are contemplated [0084]. The POSITA would have had a reasonable expectation of success in combining the teachings of Simonson and Mitsialis because each of these teachings both successfully generated MSC exosomes to treat ARDS. Therefore, the products and method as taught by Simonson et al. in view of Mitsialis et al. would have been prima facie obvious over the method of the instant application.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claim 35-46 are rejected under 35 U.S.C. 103 as being unpatentable over Simonson et al., (US20160199413A1, published on Jul 14, 2016; cited in PTO892; hereinafter “Simonson”), in view of Witwer et al (Journal of extracellular vesicles, 2019, 8(1), p.1609206; cited in PTO892; hereinafter “Witwer”) and Errichelli et al. (WO2019092145; Pub. Date: 16 May 2019; cited in PTO892; hereinafter “Errichelli”) and Mitsialis et al., (US20140065240A1, Pub. Date: Mar. 6, 2014; cited in PTO892; hereinafter “Mitsialis”), as applied to claims 35-45 above, and further in view of Ra et al. (Stem cells and development, 2011, 20(8), pp.1297-1308, cited in PTO892; hereinafter “Ra”).
As stated above regarding claim 35, Simonson teaches a method for treating a lung condition notably acute respiratory distress syndrome (ARDS) in a patient in need (abstract, [0006], [0085]), comprising administering to the patient a therapeutically effective of a pharmaceutical composition comprising clinically potent MSCs and extracellular components (primarily extracellular vesicles such as exosomes) [0006], [0097]. Simonson further discloses that the Extracellular vesicles and other paracrine factors (i.e., neurotrophic factors) are of great importance for the therapeutic efficacy of MSCs. MSCs and the vesicle population are positive for neurotrophic factors (claim 1(b),(g), [0064] [0069], [0076]). Therefore, prima facie obviousness of the combination of active agent MSC-NTFs and EXO-MSC-NTFs has been established by Simonson.
However, regarding claim 46, Simonson is silent to the volume of the pharmaceutical composition is between about 100 mL to about 120 mL. However, such was known in the prior art.
Ra discloses adipose tissue-derived mesenchymal stem cells (AdMSCs) represent an attractive and ethical cell source for stem cell therapy comprises 100-mL normal saline containing 100 million cells/each. A total of 4×108 autologous hAdMSCs per patient was introduced into the cephalic vein over 3 to 4 h. Patients were interviewed and monitored extensively on days 1, 4, and 7 and weeks 4 and 12 after transplantation and followed up for a total of 12 weeks post-transplantation (p. 1300 right col. 5th ¶ of Ra). Therefore, Ra discloses the pharmaceutical composition comprises MSCs is 100 mL.
MPEP 2143 (A) states that combining prior art elements according to known methods to yield predictable results. The rationale to support a conclusion that the claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination yielded nothing more than predictable results to one of ordinary skill in the art. KSR, 550 U.S. at 416, 82 USPQ2d at 1395. Accordingly, it would have been obvious to practice a method for treating a lung condition of Simonson and combine the administrate 100mL of the pharmaceutical composition as taught by Ra with a reasonable expectation of success. The POSITA would have been motivated at the time of filing to do so as taught by Ra because no serious adverse event associated with the intravenous administration of hAdMSCs was observed during the completion of the phase I study (p. 1306 4th ¶ of Ra). The POSITA would have had a reasonable expectation of success in combining the teachings of Simonson and Ra because each of these teachings both successfully generated MSC for immunotherapy. Therefore, the products and method as taught by Simonson et al. in view of Mitsialis et al. would have been prima facie obvious over the method of the instant application.
Hence, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MASUDUR RAHMAN whose telephone number is (571)272-0196. The examiner can normally be reached M-F 8-5 (EST).
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/MASUDUR RAHMAN/ Patent Examiner, Art Unit 1633
/FEREYDOUN G SAJJADI/ Supervisory Patent Examiner, Art Unit 1699