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 .
DETAILED ACTION
The amended claims filed on January 8, 2026, have been acknowledged. Claims 4-5 and 16 were cancelled. Claims 1, 3, 12, 17-18, and 20 were amended. Claims 1-3, 6-15, and 17-20 are pending and examined on the merits.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
Regarding claim 2, the disclosure of the prior-filed application, Application No. 63/020,532, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. This application does not provide information related to a method of treating coronavirus wherein the subject has acute lung injury, but does provide information for wherein the subject has ARDS. However, Application No. 63/146,439 does provide this information. Therefore, ARDS receives the priority date of May 5, 2020, and ALI receives the priority date of February 5, 2021.
Regarding claim 9, the disclosure of the prior-filed applications, Application No. 63/020,532, filed May 5, 2020, Application No. 63/146,439, filed February 5, 2021, and Application No. PCT/IB2021/053694, filed on May 3, 2021, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. These applications do not provide information related to a method of treating coronavirus wherein the DSCs are suspended in saline with human platelet lysate. The only mention of human platelet lysate is in reference to using 2-20% in a culture media, not saline (paragraph 0034 of 63/146,439 and PCT/IB2021/053694). However, Application No. 17/996,680, filed on November 1, 2022, did provide the above information. Therefore, human platelet lysate receives a priority date of November 1, 2022. Furthermore, Application No. 63/020,532 only identifies 5% human plasma and human albumin and not the 2.5-10% recited in claim 9. However, this expanded range is identified in Application No. 63/146,439. Therefore, 5% human plasma and human albumin receive the priority date of May 5, 2020, and the expanded range excluding 5% receives the priority date of February 5, 2021.
Regarding claim 10, the disclosure of the prior-filed applications, Application No. 63/020,532 fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Application No. 63/020,532 only identifies 2-2.5 x 106 cells/mL and not the 2-5 x 106 cells/mL recited. However, this expanded range is identified in Application No. 63/146,439. Therefore, 2-2.5 x 106 cells/mL receive the priority date of May 5, 2020, and the expanded range of greater than 2.5-5 x 106 cells/mL receives the priority date of February 5, 2021.
Regarding claim 11, the disclosure of the prior-filed applications, Application No. 63/020,532 fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Application No. 63/020,532 only identifies CD45, CD34, CD31 or HLA class II as not being expressed and not CD11b and CD19 as recited. However, these additional markers are identified in Application No. 63/146,439. Therefore, CD45, CD34, CD31 or HLA class II receive the priority date of May 5, 2020, and CD11b and CD19 receive the priority date of February 5, 2021.
Regarding claim 13, the disclosure of the prior-filed applications, Application No. 63/020,532, filed May 5, 2020, Application No. 63/146,439, filed February 5, 2021, and Application No. PCT/IB2021/053694, filed on May 3, 2021, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. These applications do not provide information related to a method of treating coronavirus wherein the DSCs have a viability of at least 85%. 63/146,439 and PCT/IB2021/053694 only identify 90% or better viability but not the expanded range of at least 85%. However, this expanded range is identified in Application No. 17/996,680, filed on November 1, 2022. Therefore, wherein the DSCs have a viability of at least 90% receives the priority date of February 5, 2021, and the expanded range between 85% and 90% receives the priority date of November 1, 2022.
Regarding claims 14-15, the disclosure of the prior-filed applications, Application No. 63/020,532, filed May 5, 2020, and Application No. 63/146,439, filed February 5, 2021, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. These applications do not provide information related to a method of treating coronavirus wherein the patient population is between about 6 months and 75 years old and wherein the subject has no history of co-morbidity or has a history of co-morbidity. Application No. 63/146,439 does provide a patient population of 14-38 with no co-morbidity and a patient population between 44 and 68 that does have a co-morbidity. However, Application No. PCT/IB2021/053694, filed on May 3, 2021 did provide information on the expanded age range. Therefore, a patient population of 14-38 with no co-morbidity and a patient population between 44 and 68 that does have a co-morbidity receives the priority date of February 5, 2021, and the expanded age ranges receive the priority date of May 3, 2021.
Regarding claims 17-20, the disclosure of the prior-filed applications, Application No. 63/020,532 fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Application No. 63/020,532 does not provide information about pulmonary ground glass opacities or pulmonary infiltration (claim 17), additional therapeutics administered in conjunction with the DSCs (claims 18 and 20), nor the identified outcomes of treatment (claim 19). However, this information was disclosed in Application No. 63/146,439. Therefore, claims 17-20 receive the priority date of February 5, 2021.
Specification
The disclosure is objected to because of the following informalities:
The specification uses the terms PD-L1 and PDL-1 and PD-L2 and PDL-2 interchangeably but the art identifies the correct identification of the terms as PD-L1 and PD-L2.
Appropriate correction is required.
Claim Objections
Claims 1, 3, and 12 objected to because of the following informalities:
The specification uses the terms PD-L1 and PDL-1 and PD-L2 and PDL-2 interchangeably but the art identifies the correct identification of the terms as PD-L1 and PD-L2.
Appropriate correction is required.
Withdrawn Claim Rejections - 35 USC § 112
The prior rejection of claim 17 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 is withdrawn in light of Applicant’s amendments to claim 17 to remove the term optionally.
The prior rejection of claims 18 and 20 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 is with drawn in light of Applicant’s amendments to claims 18 and 20 to remove the trademarked name.
Withdrawn Claim Rejections - 35 USC § 102
The prior rejection of claims 1-9, 11-12, 17-18, and 20 under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by World Intellectual Property Organization Application No. 2018/185584 (Yanay; referenced in IDS), as evidenced by de Wit et al. (Nature Reviews. 14: 523-534. 2016) is withdrawn in light of Applicant’s amendments to claim 1 to recite that the coronavirus is SARS-CoV-2.
The prior rejection of claims 1 and 16 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Berishvili et al. (Stem Cell Reviews and Reports 17:63–70. 2021, Published July 2020) is withdrawn in light of the cancellation of claim 16.
Withdrawn Claim Rejections - 35 USC § 103
The prior rejection of claims 1, 8-10, and 13 under 35 U.S.C. 103 as being unpatentable over World Intellectual Property Organization Application No. 2018/185584 (Yanay) as applied to claim 1 above, and further in view of Ringden et al. (J Stem Cell Res Ther 4: 1-5. 2014; identified in IDS) and Ringden et al. (Stem Cells 31: 592-601. 2013, identified in IDS) is withdrawn in light of Applicant’s amendments to claim 1 to recite that the coronavirus is SARS-CoV-2.
The prior rejection of claims 1 and 14-15 under 35 U.S.C. 103 as being unpatentable over World Intellectual Property Organization Application No. 2018/185584 (Yanay) is withdrawn in light of Applicant’s amendments to claim 1 to recite that the coronavirus is SARS-CoV-2.
The prior rejection of claims 1, 16, and 19 under 35 U.S.C. 103 as being unpatentable over World Intellectual Property Organization Application No. 2018/185584 (Yanay) as applied to claims 1 above, and further in view of Global News Wire (Pluristem Therapeutics, identified in IDS), Leng et al. (Aging and Disease 11: 216-228. 2020, Published April 2020; identified in IDS), and Ringden et al. (J Stem Cell Res Ther 4: 1-5. 2014), as evidenced by Sher et al. (Cell Transplantation 27: 140-150. 2018; identified in IDS) is withdrawn in light of Applicant’s amendments to claim 1 to recite that the coronavirus is SARS-CoV-2.
New Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-3, 6-15, and 17-20 are rejected under 35 U.S.C. 103 as being unpatentable over World Intellectual Property Organization Application No. 2018/185584 (Yanay), and further in view of Global News Wire (Pluristem Therapeutics, identified in IDS), Sher et al. (Cell Transplantation 27: 140-150. 2018; identified in IDS), and Ringden et al. (J Stem Cell Res Ther 4: 1-5. 2014; identified in IDS), as evidenced by Norgren et al. (Eur J Vasc Endovasc Surg 57: 538-545. 2019), Ringden et al. (Stem Cells 31: 592-601. 2013, identified in IDS), and Parekh et al. (Radiology 297: E289-E302. 2020). This is a new rejection made in response to Applicant’s amendments to claim 1. Applicant’s traversal has been fully considered but is moot in response to the new rejection.
Regarding claims 1-3, Yanay teaches a method of treating (i.e. a therapeutically effective amount) acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) by administering placental adherent stromal cells (abstract, page 1, paragraphs 3-6). Yanay teaches that the placental adherent stromal cells may be harvested from the decidua (i.e. decidual stromal cells) (page 8, paragraph 4). Yanay teaches that the ALI and ARDS can be caused by viral infection with coronavirus (page 5, paragraph 5-page 6, paragraph 2).
Yanay does not teach that the coronavirus is SARS-CoV-2 nor wherein their cells express PD-L1.
However, Global News Wire teaches that Pluristem treated seven patients experiencing COVID-19 (also known as SARS-CoV-2) induced ARDS with Pluristem’s PLX cells and saw improvements in respiratory parameters in 66% of patients (whole document).
Sher teaches that Pluristem’s PLX cells are mesenchymal-like adherent stromal cells derived from the placenta. Sher is silent as to which region of the placenta the cells are derived from but does identify the decidua as a known source of these cell types and that they made PLX-PAD cells that are derived from maternal placental tissue (which includes the decidua) (page 140, column 1, paragraph 1-page 141, column 2, paragraph 3).
Ringden (2014) teaches that they administered decidual stromal cells to a patient experiencing ARDS from an infection. 1×106 DSCs/kg were infused during five minutes. Before infusion, oxygen saturation in blood was 92% and within minutes after infusion it increased to 98% (Figure 2A). Then oxygen saturation stabilized; the requirement for oxygen decreased and it was discontinued on day +16 (Figure 2B). Chest radiography improved (Figure 3C).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used PLX-PAD cells as the decidual stromal cells in the method of treating coronavirus of Yanay to treat patients experiencing ARDS from SARS-CoV-2 to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to use PLX-PAD cells as the decidual stromal cells to treat SARS-CoV-2 with a reasonable expectation of success because Yanay identifies that decidual stromal cells can be used to treat ARDS or acute lung injury caused by coronavirus infections and Pluristem successfully reduces to practice that PLX cells can be used to treat Covid-19 in patients with severe ARDS and saw improved respiratory outcomes. Additionally, Ringden has previously shown that decidual stromal cells can treat ARDS caused by infection and improve respiratory function. Therefore, it would have been obvious that one could use decidual stromal cells to treat patients that experience Covid-19 induced ARDS. It would have been obvious to administer PLX-PAD cells to patients experiencing SARS-CoV-2 induced ARDS as PLX cells have been shown to improve symptoms associated with COVID-19 infection, Ringen teaches that decidual stromal cells alleviate symptoms associated with ARDS caused by infection, and Sher identifies PLX-PAD as mesenchymal-like adherent stromal cells derived from the maternal placenta and would encompass decidual stromal cells.
Regarding expression of PD-L1, Norgren evidences that PD-L1 is expressed by PLX-PAD cells (page 540, column 1, paragraph 2 and Figure 1).
Regarding claim 6, Yanay teaches that the decidual stromal cells can be administered to the subject between 1-20 days of after diagnosis of ARDS or ALI intravenously (page 7, paragraph 6 and claims 1 and 34).
Regarding claim 7, Yanay teaches that the decidual stromal cells can be administered in a series of injections with a course of treatment lasting several days (page 42, paragraphs 1-2). Therefore, this encompasses scenarios wherein two injections are administered to the patient at least two days apart.
Regarding claim 8, Yanay teaches that dosing can be 80 million cells per administration (page 41, paragraph 7-page 42, paragraph 1). Yanay teaches that the subject can be an adult human (page 43, paragraph 5). Although Yanay is silent as to the dose per kg, the average male adult is around 80 kg which would equate to 1 x 106 cells/kg.
Regarding claim 9, Yanay teaches that for injection, the described cells may be formulated in aqueous solutions, e.g. in physiologically compatible buffers such as Hank's solution, Ringer's solution, or physiological salt buffer (which includes saline), optionally in combination with medium containing cryopreservation agents.
As an example, Yanay teaches that the cell suspension underwent concentration and washing, using suspension solution (5% w/v human serum albumin [HSA] in isotonic solution) as the wash buffer, and diluted 1:1 with 2X 3D-Freezing solution (20% DMSO v/v and 5% HSA w/v in isotonic solution) to a final concentration of 10-20x106 cells/ml, in isotonic solution containing 10% DMSO v/v and 5% HSA w/v. The temperature of the vials was gradually reduced, and the vials were stored in a gas-phase liquid nitrogen freezer.
Yanay identifies an example of an isotonic buffers as Hank's Balanced Salt Solution (HBSS; Life Technologies) but recites it is only one of many buffers that may be used. Yanay identifies [e.g., phosphate-buffered saline (PBS) or Hank's buffer] as physiological buffers (page 8, paragraph 4, page 35, paragraph 2, page 41, paragraph 3, page 47, paragraph 6).
Therefore, PBS is an isotonic buffer that can be used in their washing solution with 5% human albumin or in the cryopreservation solution with 5% human albumin.
Regarding claims 10 and 13, Yanay teaches that they administered 1 x 106 decidual stromal cells to a mouse model of acute lung injury by LPS administration and 150 x 106 decidual stromal cells to a patient suffering acute lung injury (Examples 5 and 6).
Yanay is silent as to the concentration of the decidual stromal cells per mL and viability of the cells.
However, Ringden (2014) teaches that they administered decidual stromal cells to a patient experiencing ARDS from an infection. 1×106 DSCs/kg were infused during five minutes. Before infusion, oxygen saturation in blood was 92% and within minutes after infusion it increased to 98% (Figure 2A). Then oxygen saturation stabilized; the requirement for oxygen decreased and it was discontinued on day +16 (Figure 2B). Chest radiography improved (Figure 3C). Ringden 2014 teaches that their procedure for isolation, expansion, and freeze-thawing of DSCs using good manufacturing practice was identified in Ringden (2013). Ringden (2014) teaches that their thawed cells for infusion were over 90% viable and express the same markers as claimed (claims 23-24) in Yanay (CD29, CD44, CD73, CD90, and CD105 but negative for hematopoietic markers CD45, CD14, and CD34) (page 1, column 2, paragraph 2-page 4, column 1, paragraph 1).
Ringden (2013) evidences the methods of isolation, expansion, and freeze-thawing of DSCs using good manufacturing practice used in Ringden (2014). For infusion of the decidual stromal cells, the cells were thawed at 37°C and diluted in PBS-EDTA buffer supplemented with 5% AB-plasma (obtained from the local blood bank) in 50-ml Falcon tubes (BD). The cells were counted and resuspended in NaCl infusion solution with 5% AB-plasma at a concentration of 2 x 106 cells per ml. The solution was filtered through a 70-μm cell strainer (BD) before it was transferred to a heparinized syringe. Cells were infused intravenously for 5 minutes via a central venous line (page 593, column 1, paragraph 3-page 595, column 1, paragraphs 3).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the good manufacturing practice isolation, expansion, freeze-thawing, and infusion method of Ringden (2013) and Ringden (2014) for treating ARDS in a human patient experiencing ARDS from COVID-19 to arrive at the instantly claimed invention. One of ordinary skill in the art would have a reason to use the method of Ringden (2013 and 2014) with a reasonable expectation of success because Ringden (2014) has successfully reduced to practice that infusing thawed cells resuspended in NaCl infusion solution with 5% AB-plasma at a concentration of 2 x 106 cells per ml led to near immediate improvements in oxygen saturation, and eventual recovery, in a patient experiencing infection induced ARDS and that this is considered a good manufacturing process for human treatment. Therefore, it would have been obvious to use the methods of isolation, expansion, freeze-thawing, and infusion of Ringden to treat ARDS in other patients. Because the prior art teaches all of the elements of the claimed invention, there is a reasonable expectation of success.
Regarding claims 11-12, Yanay teaches that the decidual stromal cells express CD29 and do not express CD45 (page 18, paragraph 1). As the PLX-PAD cells of Pluristem are also decidual stromal cells. They would express the same markers.
Regarding claims 14-15, Yanay teaches that the subject can be an adult subject such as a subject over 25 or an elderly subject (page 43, paragraph 5).
Yanay is silent as to whether the subjects have a co-morbidity or not.
However, it would have been well understood that the subject could experience co-morbidities or not as the patient population identified by Yanay would consist of both. For example, a ~25 year old is less likely to have a co-morbidity while a ~65 year old is more likely to have a co-morbidity (such as diabetes or heart/pulmonary disease). Therefore, it would have been obvious based on the patient population identified by Yanay that one could treat individuals with and without co-morbidities.
Regarding claim 17, Yanay teaches that ARDS patients can exhibit ground-glass opacification from pneumonia, as stated supra, this can be caused by coronavirus (page 5, paragraph 2). Parekh evidences that ground-glass opacities are a common occurrence in COVID-19 patients with greater than 88% of COVID patients having ground glass opacities identified by chest CT (abstract and Table 1). Therefore, it would have been well understood that COVID-19 patients would also exhibit these ground glass opacities.
Regarding claims 18 and 20, Yanay teaches that since non-autologous cells may in some cases induce an immune reaction when administered to a subject, one may utilize suppressing the recipient immune system before transplantation to reduce the likelihood of rejection. Examples of immunosuppressive agents include hydroxychloroquine (page 40, paragraphs 2-3).
Regarding claim 19, Pluristem teaches that patients had improved respiratory function and were progressing towards weaning off the ventilator and Ringden teach that there was improved oxygen saturation rates in patients that were administered decidual stromal cells. Therefore, it naturally flows that administering decidual stromal cells to a patient with ARDS from SARS-CoV-2 would also cause oxygen saturation to improve.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KEENAN A BATES whose telephone number is (571)270-0727. The examiner can normally be reached M-F 7:30-5:00.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Doug Schultz can be reached at (571) 272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KEENAN A BATES/Examiner, Art Unit 1631
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631
Prosecution Insights