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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 04/13/2026 has been entered.
Claims Status
Claim 1,and 10 are amended.
Claim 15 is new.
Claim 1-11, and 13-15 are under examination.
Edited Rejections Necessitated by Claims Amendments
Claim Interpretation
It is noted that in page 3 ( 1st paragraph of "Detailed description") of instant specification that the administered Cells (I) are presumed to be Multipotent Adult progenitor cells (MAPC). Instant specification also refer to this MAPC as MultiStem (See page 15- 3rd paragraph of instant specification). Therefore, for examination purpose, Cell (I) is understood as referring to MAPC and MultiStem.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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 1-11, and 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over Anthony et al (US 2011/0305638 A1) in view of Mitchell et al ( WO 2021/203061 A1, filed 04/02/2021 ; with priority to 63/005178 filed 04/03/2020) and Lehmann et al ( Athersys, with a public disclosure of 01/23/2019).
Regarding claims 1-4, and 10-11, Anthony et al teach cell-based therapy to treat any disease involving inflammation, such as ARDS. (See [0052]. Anthony’s method involves administering Multipotent adult stem cells (MAPC) (trade marketed as MultiStem) to a subject in need of therapy. The MAPC’s of Anthony reads on Cell (I) recited in instant claim 1. Anthony et al suggest that the cells to be administered in a therapeutically effective amount and for a sufficient time to treat inflammation. Anthony et al disclose that the cells of the invention (i.e. MultiStem) are non-embryonic stem, non-germ cells that have undergone at least 10-40 cell doublings in culture, and wherein the cell further express telomerase and/or oct4,not transformed, not tumorigenic, and have a normal karyotype. ( See claim 15, and paragraphs [0015]-[0019], and [0025]). Anthony et al also disclose that the cells can differentiate into at least one cell type of at least two of the endodermal, ectodermal, and mesodermal embryonic lineages.(See paragraph [0020]).
Anthony et al do not teach administering MultiStem cells to treat ARDS caused by coronavirus.
Mitchell et al teach cell-based therapy to treat ARDS caused by coronavirus infection (e.g. COVID-19/SARS-CoV-2) in a subject having coronavirus infection. The method involves administering to the subject hematopoietic stem cells in an amount effective to treat the disease. Mitchell et al also teach that the hematopoietic stem cells may be administered intravenously. According to Mitchell et al, hematopoietic stem cells must be HLA-matched to the recipient before being administered. ( See the 2nd paragraph on page 3). Mitchell et al do not teach or suggest utilizing MAPC (i.e. Cell (I)) to treat coronavirus infection. (See the section “ SUMMARY” on page 1, it should be noted that Mitchell’s teachings are also disclosed in 63/005178, e.g. on page 1 ).
Lehmann et al demonstrate that intravenous administration of MultiStem® cell therapy to patients suffering from acute respiratory distress syndrome (ARDS) is tolerated and has a favorable safety profile. Lehmann et al go on to explain that the administration of MultiStem has therapeutic benefits in patients suffering from ARDS. According to Lehmann et al, “ the MultiStem treatment was associated with lower mortality and a greater number of ventilator-free and intensive care unit (ICU) free days in the first month following diagnosis relative to patients receiving placebo. Furthermore, analysis of initial biomarker data reflects lower levels of inflammatory markers/cytokines following MultiStem treatment, an expected mechanism of action in this patient population”. ( See the 3rd paragraph on page 1). Lehmann et al further state that the MAPC can be administered without the need for tissue matching or the need for immune suppression. Lehman et al also suggest that “ MAPC can be used to treat patients, including suffering from serious diseases and conditions with unmet medical need”. ( See “ About MultiStem on page 2)
It is noted that Lehmann et al and Anthony et al teach the administration of MultiStem to treat patients suffering from ARDS, but fails to suggest the use of the MultiStem to treat patients suffering from coronavirus infection. However, instant claims would have been obvious to one of ordinary skill in the art, as there was some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Anthony et al teach cell-based therapy to treat any disease involving inflammation, such as ARDS, but fails to specifically suggest the use of MAPC to treat coronavirus infection. Mitchell et al teach hematopoietic stem cells can be utilized to treat patients with ARDS caused by coronavirus infection(e.g. COVID-19), and state that the cells must be HLA-matched to the recipient before being administered. Lehmann et al demonstrate that the intravenous administration of MultiStem® cell therapy to treat patients who are suffering from ARDS provides therapeutic benefit, is tolerable, has a favorable safety profile, and does not need to be HLA-matched to the recipients. Lehman et al also suggest that “ MAPC can be used to treat patients, including suffering from serious diseases and conditions with unmet medical need”. Thus, one would have been motivated to use MAPC, as disclosed by Anthony and Lehmann, for the treatment of ARDS caused by coronavirus, as taught by Mitchell et al, because COVID-19 is a serious disease with unmet medical needs. There would be a reasonable expectation of success in replacing Mitchell et al’s cells with Anthony and Lehmann’s cells because prior art demonstrated that administering MAPC is tolerable, has a favorable safety profile, and does not need to be HLA-matched to the recipients.
It is noted that Applicants amended claim 1 to recite “wherein the treating the viral-induced ARDS includes reducing one or more of IL-2 or IL-7”. However, this is a functional limitation which is considered to be prima facie present per natural law of cell biology in the combined teachings of the cited prior arts and they reasonably fulfill the functional limitation that is being claimed. In other words, the recited functional limitation is considered to be an inherent property as it flows from performing the active steps of the method “ i.e. administering MultiStem to treat patients suffering from ARDS”, and even if the functional limitation was not recognized by the prior arts at the time the invention was filed, according to the MPEP, this functional outcome would flow naturally from following the suggestion of the prior art and cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). For a method claim comprising a functional outcome, it is not required that a prior art would disclose/recognize the functional outcome before a prima facie case of anticipation or obviousness would be established. While the references do not show a specific recognition of the recited functional outcome, its discovery by appellants is tantamount only to finding an inherent property.
As per the MPEP “ there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003).
Regarding to claims 5-6, Anthony et al also disclose that the cells of the invention are human and can be derived from bone marrow. (See paragraph [0129] and [0083]).
Regarding to claims 7-9, Anthony et al teach administering cells that have undergone for example, 10-20, 20-30, 30-40, 40-50 or more cell doublings. (See paragraph [0148]).
Regarding to claims 13-14, Anthony et al disclose that the cells of the invention can be used to treat humans, and the route of administration may include intravenous-administration. (See claim 24, and paragraph [0156]).
Regarding claim 15, the claim recites functional outcomes that result from administering a sufficient amount of Multistem to a patient with ARDS caused by coronavirus. These functional outcomes are considered prima facie present per natural law of cell biology in the combined teachings of the cited prior arts and they reasonably fulfill the functional limitation that is being claimed. In other words, the recited functional limitation is considered to be an inherent property as it flows from performing the active steps of the method “ i.e. administering MultiStem to treat patients suffering from ARDS”, and even if the functional limitation was not recognized by the prior arts at the time the invention was filed, according to the MPEP, this functional outcome would flow naturally from following the suggestion of the prior art and cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parte Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). For a method claim comprising a functional outcome, it is not required that a prior art would disclose/recognize the functional outcome before a prima facie case of anticipation or obviousness would be established. While the references do not show a specific recognition of the recited functional outcome, its discovery by appellants is tantamount only to finding an inherent property.
As per the MPEP “ there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003).
Response to Arguments
Applicant's arguments filed 04/13/2026 have been fully considered but they are not persuasive.
Applicant argue that a person having ordinary skill in the art would not consider it obvious to successfully treat viral-induced ARDS induced by a coronavirus by merely substituting HSCs with MAPCs as the two cell types have different mechanisms of action.
Examiner’s Response to Traversal: Applicant’s arguments have been carefully considered but are not found persuasive. This is because the current rejection, as it stands, includes prior art references that disclosed all of the elements recited in the instant claims; provided motivation for one of ordinary skill in the art to combine the prior art references to produce the claimed invention; and provided a reasonable expectation that the combination would be successful. In this case, Anthony et al is cited to demonstrate that MultiStem® cells can be administered to a subject to treat any disease involving inflammation, such as ARDS, while Mitchell et al is cited to supplement Anthony by teaching that cell-based therapy (i.e. hematopoietic stem cells) may be used to treat ARDS caused by coronavirus infection (e.g. COVID-19). Mitchell et al also clearly cautioned that hematopoietic stem cells must be HLA-matched to the recipient before being administered. On other hand, Lehman et al is cited to further supplement Anthony by demonstrating that intravenous administration of MultiStem® cell therapy to patients suffering from ARDS regardless of its cause is tolerated and has a favorable safety profile. Lehman et al also clearly suggested that “ MultiStem® can be used to treat patients, including suffering from serious diseases and conditions with unmet medical need”. Clearly, the teachings of prior arts provide one with ordinary skill in the art with the motivation to use MultiStem® to treat ARDS, because both Anthony and Lehmann demonstrated that administering MultiStem® is tolerable, has a favorable safety profile, can be used to treat any disease involving ARDS, and does not need to be HLA-matched to the recipients. There is a clear suggestion by prior art to use MultiStem® cells to treat ARDS regardless of its cause. Therefore, once COVID-19 is recognized as a cause of ARDS, an ordinary skill in the art would have found it obvious to evaluate known ARDS therapies, including the claimed stem cell therapy for the treatment of ARDS caused by COVID-19. There is nothing in the teachings of the prior arts that would turn away an ordinary skill in the art from using the MultiStem® for the treatment of ARDS caused by coronavirus. Also, the fact that MultiStem® has been shown to have a safe profile and do not need to be HLA-matched to the recipient provide one with ordinary skill in the art with the motivation to use these cells to treat ARDS caused by coronavirus infection, and with a high expectation of success. In other words, the prior arts teach administering Multistem to treat ARDS in a subject in need. Since Covid-19 infection is known to cause ARDS, it would have been obvious to use the disclosed Multistem cell therapy to treat COVID-19- associated ARDS and with a reasonable expectation of success.
As per the MPEP, obviousness can be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed.Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
The court held “it is not necessary in order to establish a prima facie case of obviousness . . . that there be a suggestion or expectation from the prior art that the claimed [invention] will have the same or a similar utility as one newly discovered by applicant,” and concluded that a prima facie case can be established when “[t]he art provided the motivation to make the claimed compositions in the expectation that they would have similar properties.” 919 F.2d at 693, 16 USPQ2d at 1901 (emphasis in original).
Applicant further argue that the cited references appear to be silent as to reducing cytokines recited in amended independent claim 1. Rather, Mitchell discloses the opposite: "administering one or more of IL-7, IL-2, IL-15, or IL-21 and neither Anthony nor Lehmann mention IL-2 or IL-7.
Examiner’s Response to Traversal: Applicant’s arguments have been carefully considered but are not found persuasive. This is because, as noted previously, the amendment recites a functional outcome e.g. an endpoint that would result from administering the claimed cells to the subject suffering from ARDS. It should be noted that the recited functional outcome is considered prima facie present per natural law of cell biology in the combined teachings of the cited prior arts and they reasonably fulfill the functional limitation that is being claimed. In other words, the recited functional limitation is considered to be an inherent property as it flows from performing the active steps of the method “ i.e. administering MultiStem to treat patients suffering from ARDS”, and even if the functional limitation was not recognized by the prior arts at the time the invention was filed, according to the MPEP, this functional outcome would flow naturally from following the suggestion of the prior art and cannot be the basis for patentability when the differences would otherwise be obvious. See Ex parted Obiaya, 227 USPQ 58, 60 (Bd. Pat. App. & Inter. 1985). For a method claim comprising a functional outcome, it is not required that a prior art would disclose/recognize the functional outcome before a prima facie case of anticipation or obviousness would be established. While the references do not show a specific recognition of the recited functional outcome, its discovery by appellants is tantamount only to finding an inherent property.
As per the MPEP “ there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003).
Conclusion
No claim is allowed.
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/FATIMAH KHALAF MATALKAH/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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