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
1. The amendment filed 01/20/2026 has been entered. Claims 1 – 4, 6 – 19, and 21 – 25 remain pending and are under consideration. Claims 5 and 20 have been canceled.
Priority
2. This application is a National Stage entry from PCT application PCT/US2021049535 filed on 09/08/2021 and claims domestic benefit to provisional application 63/075780 filed on 09/08/2020.
Withdrawn Specification
3. The objection to the specification for improper trade name or marker usage is withdrawn in view of Applicant’s amendment to the specification.
Withdrawn Claim Objections
4. The objection to claim 2 because of the following informalities: in line 2, “intranasally, intraperitoneally,” should read “intranasally, or intraperitoneally,” is withdrawn in view of Applicant’s amendment to the claim.
5. The objections to claim 3 are withdrawn in view of Applicant’s amendment to the claim.
6. The objection to claim 4 is withdrawn in view of Applicant’s amendment to the claim.
7. The objections to claim 5 are rendered moot in view of Applicant’s cancelation of the claim.
8. The objections to claim 6 are withdrawn in view of Applicant’s amendment to the claim.
9. The objections to claim 7 are withdrawn in view of Applicant’s amendment to the claim.
10. The objection to claim 8 is withdrawn in view of Applicant’s amendment to the claim.
Withdrawn Duplicate Claims Warning
11. All previous duplicate claims warnings have been withdrawn in view of Applicant’s amendment to the claims.
Withdrawn Claim Rejections
12. The rejection of claims 5 and 20 under 35 U.S.C. 112(a) is rendered moot in view of Applicant’s cancellation of these claims.
13. The rejection of claim 14, 16, 17, 18, 21, and 23 – 25 are rejected under 35 U.S.C. 112(b) is withdrawn in view of Applicant’s amendment to the claims.
14. The rejection of claims 19 and 21 under 35 U.S.C. 101 is withdrawn in view of Applicant’s amendment to claim 19.
15. The rejection of claims 1 – 4, 9 – 18, and 22 – 25 under 35 U.S.C. 102(a)(1) and (a)(2) is withdrawn in view of Applicant’s amendment to the claims.
16. The rejection of claim 5 under 35 U.S.C. 103 is rendered moot in view of Applicant’s cancelation of the claim.
17. The rejection of claim 20 under 35 U.S.C. 103 is rendered moot in view of Applicant’s cancelation of the claim.
18. The rejection of claim 20 rejected on the ground of nonstatutory double patenting is rendered moot in view of Applicant’s cancelation of the claim.
Maintained Claim Objections
19. Claim 2 remains objected to because of the following informalities: in line 1, “wherein the infusing the composition further comprises” should read “wherein the infusing comprises”. Appropriate correction is required.
Maintained 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.
20. Claims 1 – 4 and 6 – 18 remain rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating ARDS in a subject, comprising infusing intravenously or intranasally a composition comprising autologous or allogeneic mesenchymal stem cells in an amount of 100 ± 20 x 106 cells in two doses where the second dose is administered 2 days after the first dose to a subject having acute respiratory distress syndrome (ARDS), wherein the mesenchymal stem cells express at least three cell markers selected from the group consisting of CD29, CD73, CD90, CD166, SSEA4, CD9, CD44, CD146, or CD105; and wherein the mesenchymal stem cells do not express at least five cell markers selected from the group consisting of NANOG, CD45, CD34, CD14, CD79, CD106, CD86, CD80, CD19, CD117, Stro-1, or HLA-DR, does not reasonably provide enablement for a method of treating the breadth of claimed respiratory conditions, by the breadth of claimed routes of infusion. 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 and use the invention commensurate in scope with these claims. Although maintained, note that the rejection is revised in view of Applicant’s amendments to the claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01(a)). The court in Wands states: "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue,' not 'experimentation.' " (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (a) the breadth of the claims, (b) the nature of the invention, (c) the state of the prior art, (d) the level or ordinary skill in the art, (e) the level of predictability in the art, (f) the amount of direction provided by the inventor, (g) the existence of working examples, and (h) the quantity of experimentation needed to make use of the invention based on the content of the disclosure. While all of these factors are considered, a sufficient amount for a prima facie case are discussed below.
(a) The breadth of the claims: The claims broadly recite “respiratory condition” and “infusing” and therefore the claims read on any respiratory condition and any route of infusion. The claims recite “stem or progenitor cells” but require the cells express 3 out of 9 recited markers and not express 5 out of 12 recited markers. Thus, the claims read on autologous, allogeneic, and xenogeneic stem and progenitor cells. The claims do not require dose or dosage range of cells that are administered and therefore read on any and all amounts of cells. Consequently, the breadth of the claims is expansive.
It is noted that the instant rejection is based on three separate issues:
(i) absence of an enabling disclosure of treating any respiratory condition by infusing a composition comprising stem or progenitor cells to a subject having any respiratory condition;
(ii) absence of an enabling disclosure for treating any respiratory condition by infusing by any route a composition comprising stem or progenitor cells to a subject having any respiratory condition;
(iii) absence of an enabling disclosure for treating any respiratory condition by infusing any dose of stem or progenitor cells with any dosing schedule.
(b) The nature of the invention: The nature of the invention is treating respiratory disorders by administering umbilical cord-derived stem cells. (page 11, lines 25 – 34; page 14, lines 27 – 34; page 15, lines 1 – 11).
(c) The state of the prior art:
Regarding issue (i) of absence of an enabling disclosure of treating any respiratory condition, the state of the art teaches that mesenchymal stem cells that express CD105, CD90, and CD73 and lack expression of CD45, CD34, and CD14 are useful for treating ARDS, allergic asthma, emphysema, and silicosis in part because they have immunomodulatory properties that attenuate inflammation (Silva, Luisa HA, et al. Stem cell research & therapy 9.1 (2018): 45; page 1, left col. and right col. para. 1 – 2). However, the state of the art teaches that treatment of lung cancer is unsuccessful because the cells increased tumor metastasis and inhibited innate and adaptive immunity (Gazdic M, et. al. Stem Cells Int. 2017;2017:6294717; page 3, right col. last para.; page 4, left col. para. 1; page 9, left col. para. 5 and right col. para. 2). The prior art teaches that treatment of advanced pulmonary sarcoidosis is unsuccessful because patients did not experience a clinical benefit with respect to lung function (Baughman, Robert P., et al. Sarcoidosis, Vasculitis, and Diffuse Lung Diseases: Official Journal of WASOG 32.2 (2015): 106-114; page 107, left col. last para. and right col. para. 4; page 109, left col. para. 2; Figure 1). The state of the art does not appear to provide any evidence as to the treatment of drowning, which is indeed a respiratory condition, with mesenchymal stem cells. Thus, the prior art teaches the claimed breadth of respiratory conditions cannot be treated with mesenchymal stem cells.
Regarding issue (ii) of absence of an enabling disclosure for treating any respiratory condition by infusing by any route a composition comprising stem or progenitor cells, the state of the art teaches intravenous infusion of MSCs is successful for treating emphysema (Silva; page 7, left col. para. 2). However, the state of the art teaches that intraarterial administration of MSCs prevents stem cells from becoming trapped in the lungs, as opposed to intravenous infusion which traps MSCs in the lung (Watanabe, Mitsuyoshi, et. al. Brain circulation 2.3 (2016): 114-117; page 115, left col. para. 2). Therefore, intraarterial infusion would prevent targeting portions of the respiratory system with MSCs for treatment. The prior art teaches the size of MSCs limits the efficacy of intraarterial delivery and could cause compromised regional cerebral blood flow due to the presence of larger MSCs (Watanabe; page 115, left col. para. 2). The prior art teaches that while intravenous infusion of MSCs inhibited deterioration of lung function in an animal model of COPD, intratracheal administration of MSCs had no effect (Broekman W, et. al. Thorax. 2018 Jun;73(6):565-574; page 569, Table 1, entry 2). Thus, the state of art teaches the claimed breadth of routes of administration would limit the treatment with MSCs because MSCs would not persist in the lungs and would not treat all respiratory infections.
Regarding issue (iii) of absence of an enabling disclosure for treating any respiratory condition by infusing any dose of stem or progenitor cells with any dosing schedule, the state of the art teaches doses of 105 – 106 MSCs for treating ARDS where administering MSCs 4 hours after exposure to radiation increased survival rates (Silva, Table 2, “Radiation-induced ARDS”). However, the state of the art teaches the potency of MSC therapy is limited which may be due to the amount of MSCs inoculated, administration late in the course of lung disease, low MSC survival rates in vivo and impaired MSC potency/biological activity and that the success of MSC therapy requires an appropriate number of cells (Silva; page 1, right col. para. 2; page 2, left col. para. 1 and last para.; Figure 1). The prior art teaches MSC engraftment in the lungs can hinder cell therapy as they are cleared from the lung tissue in 24 h (Silva; page 2, left col. para. 2). Thus, the state of the art teaches the claimed breadth of doses of stem or progenitor cells would not be effective for treating any respiratory condition because MSCs have low survival rates in vivo.
(d) The level of skill in the art:
The level of skill in the art of treating respiratory conditions is high, as an artisan in this art needs specialized knowledge such as a postgraduate degree (Ph.D. and/or M.D.) given the complex nature of the respiratory system. An artisan in the area of therapeutic stem and progenitor cells would have experience in characterizing mesenchymal stem cells based on the expression and absence of expression of specific markers and screening mesenchymal cells for anti-inflammatory activity in vitro. However, developing a therapeutic method for treating respiratory conditions is generally not well-known or routine given the complexity of the respiratory system, determining effective dosages, the route of dosing, the timing of dosing, and the pharmacokinetics of administered mesenchymal stem cells.
Determining how mesenchymal stem cells will impact the respiratory system is not routine. There is no way to target only cells affected by a respiratory condition while avoiding effects on normal, non-affected cells that may result in a different or unwanted effect when administering mesenchymal stem cells. Further, the respiratory system acts in concert with other systems such as the circulatory system and the immune system and the pathology of many respiratory diseases involve these systems.
(e) The level of predictability in the art:
Regarding issue (i) of absence of an enabling disclosure of treating any respiratory condition, while the use of MSCs for treating ARDS is well known, the use of MSCs for treating all other respiratory conditions within the scope of the claim is not predictable. For example, while MSCs are used to treat ARDS, a clinical study found that MSCs were ineffective in improving the in moderate-to-severe and severe-to-very severe COPD (Broekman W, et. al. Thorax. 2018 Jun;73(6):565-574; page 570, right col. last para; page 571, left col. para. 1 – 2). Thus, it is unpredictable whether MSCs used for one type of respiratory condition can be used to treat another respiratory condition even when the conditions share symptoms (shortness of breath, cough, fatigue). The predictability of applying MSCs for treating any respiratory condition encompassed by the instant claim would be low given that MSCs were ineffective for treating two different respiratory conditions with shared symptoms.
Regarding issue (ii) of absence of an enabling disclosure for treating any respiratory condition by infusing by any route a composition comprising stem or progenitor cells, while intravenous infusion of MSCs is well known, the use of any other route of administration within the scope of the claim is not predictable. For example, a study found that in an animal model of COPD intravenous infusion of MSCs inhibited deterioration of lung function but intratracheal administration had no effects (Broekman W, et. al. Thorax. 2018 Jun;73(6):565-574; page 569, Table 1, entry 2). Thus, it is unpredictable whether MSCs administered by one route can be administered by another route and treat a respiratory condition even when the respiratory condition is the same in both routes of administration. The predictability of administering MSCs by any route encompassed by the instant claim would be low given that MSCs administered intravenously showed some benefit but when administered intratracheally in the same animal model showed no benefit.
Regarding issue (iii) of absence of an enabling disclosure for treating any respiratory condition by infusing any dose of stem or progenitor cells with any dosing schedule, the use of any dose of MSCs on any dosing schedule within the scope of the claim is not predictable. For example, studies using MSCs to treat an animal model of COPD showed that a dose of 0.5 x 106 MSCs administered intravenously four times two weeks apart showed no effect on lung function parameters but the same dose administered three times within two weeks showed protective effects with decreased inflammation, less apoptosis and fibrosis (Broekman; page 568, Table 1, compare entry 8 to entry 9). Further a clinical trial for treating COPD in humans showed that infusions of 100 x 106 allogeneic cells showed no clinical benefit which may have been due to the dosage and treatment regimen (Broekman; page 570, right col. last para.). The predictability of administering any dose of MSCs using any dosing regimen encompassed by the instant claim would be low given that the same dose administered by different regimens in an animal model of COPD showed some benefit when administered three times at 5 – 7 days apart but showed no benefit when administered four times two weeks apart.
(f), (g) The amount of direction provided by the inventor and the existence of working examples:
The specification provides an example of a clinical trial treating COVID-19 patients with ARDS with allogeneic mesenchymal stem cells by intravenous infusions at a dosage of 100 ± 20 x 106 cells (page 19, lines 6 – 34; page 22, lines 11 – 22). The specification does not provide any other working examples for treating any other respiratory condition with xenogeneic mesenchymal stem cells by any other route of infusion.
(f) The amount of direction provided by the inventor:
The specification shows that MSCs treat ARDS. Since MSCs are well known to treat ARDS, there is a nexus between these results and the treatment of ARDS, but not to the full scope of the method as claimed.
(g) The existence of working examples:
The specification shows that administration of 100 ± 20 x 106 allogeneic MSCs twice at two days apart to subjects with ARDS was found to be safe and at 31 days post first infusion, patient survival was 91% in the treatment groups compared to 42% in the control group (page 28, lines 12 – 19). The specification does not provide any additional examples or guidance on how to use the MSCs to treat all other respiratory condition as recited in the claim.
Thus, the specification provides sufficient teachings only for the enablement of treating ARDS by intravenous or intranasal infusion of 100 ± 20 x 106 allogeneic or autologous MSCs twice at two days apart. The prior art provides no compensatory guidance, since attempts to treat other respiratory conditions, such as lung cancer, sarcoidosis, and COPD, with MSCs have been unsuccessful, it would require undue experimentation to practice the invention as broadly claimed.
(h) The quantity of experimentation needed to make use of the invention based on the content of the disclosure:
The amount of experimentation would be undue because it would require determining which respiratory conditions recited in the instant claim would be reasonably treated with MSCs. Since, as discussed above, it is not routine to determine how MSCs will act on the respiratory system to treat any respiratory condition, knowing only that the MSCs of the instant claims treat ARDS would mean that significant experimentation would be required to determine which other respiratory conditions MSCs could treat and at what dose and at what dosing regimen. This is because one cannot extrapolate between the working example in the specification and the treatment of other respiratory disorders claimed and since there is little guidance with respect to the use of MSCs for treating any other respiratory condition besides ARDS. Thus, the full scope of claim 1 is not enabled by the disclosure.
Maintained Claim Rejections - 35 USC § 103
21. Claim(s) 19 and 21 remain and claims 22 – 25 are rejected under 35 U.S.C. 103 as being unpatentable over Patel (WO-2013102219-A1; Filed 12/31/2012; Published 07/04/2013; previously cited) hereinafter Patel as evidenced by as evidenced by Patel-2013 (Patel, Amit N., et al. Cell Transplantation 22.3 (2013): 513-519.), hereinafter Patel-2013 in view of Xu (Qiang, W. A. N. G., et al. Chinese medical journal 125.11 (2012); ; previously cited), hereinafter Xu in view of Smith (Smith, J. Robert, et al. Stem cells international 2016.1 (2016): 6810980; previously cited), hereinafter Smith. Although maintained, note that the rejection is revised in view of Applicant’s amendments to claims 22 – 25 that now depend from claim 19 and are included in this rejection.
Regarding claim 19 and “mesenchymal stem cells” of claim 21 and 22, Patel teaches an isolated population of cells for treating COPD and teaches the cells express CD29, CD73, CD90, CD166, SSEA4, CD9, CD44, CD146, and CD105 and do not express CD45, CD34, CD14, CD79, CD106, CD86, CD80, CD19, CD117, Stro-1, and HLA-DR (page 4, lines 1 – 3; page 8, lines 18 – 34; page 14, lines 27 – 30; page 16, Example 2; page 17, Example 3 – 4; page 20 – 21, Example 9; Figures 3 – 4). Mesenchymal stem cells isolated from the subepithelial layer of umbilical cord express CD9, SSEA4, CD44, CD90, CD166, CD73, and CD146 and do not express CD14, CD34, CD45, STRO-1, and Nanog as evidenced by Patel-2013 (Abstract; page 518, left col. para. 1). Patel teaches in Table 3 that intravenous infusion and inhalation of the cells increases lung function as measured by comparing FEV1/FVC pre to FEV1/FVC post. Patel does not teach the cells are in a first container or a dilution buffer in a second container or the kit is cryopreserved of claim 19.
Regarding claims 23 – 25, Patel teaches the cells are capable of differentiation into a variety of cell types including chondrocytes (claim 23), osteocytes (claim 24), and cardiomyocytes (claim 25) (page 2, lines 3 – 7; Figures 8 – 10; page 8, lines 1 – 9; page 12, lines 30 – 34; page 13, lines 1 – 20).
Regarding “dilution buffer” of claim 19, Xu teaches administering mesenchymal stem cells (MSCs) in phosphate buffered saline (PBS) to treat acute lung injury (page 2013, right col. para. 2; Figure 1). Xu teaches administration of the MSCs in PBS led to significant improvement of the histological appearance of the lung as well as the lung injury scores (page 2016, right col. para. 1). Xu teaches the MSCs reduced the inflammatory response, maintained integrity of the alveolar-capillary barrier, and reduced the adhesion and secretion of inflammatory cells (page 2017, left col. para. 1). Xu teaches MSCs are a potential therapy for ARDS (page 2017, left col. last para.). Xu teaches ARDS is a major cause of acute respiratory failure in crucially ill patients with an overall mortality as high as 40% (page 2012, left col.). Xu does not teach the kit is cryopreserved of claim 20. One would have been motivated to combine the teachings of Patel regarding treating a respiratory condition with an isolated population of MSCs with the teachings of Xu regarding administering isolated MSCs in PBS to treat acute lung injury because Xu teaches MSCs are a potential therapy for ARDS and the MSCs in PBS reduced lung injury.
Regarding the kit is “cryopreserved” of claim 19, Smith teaches isolated MSCs from umbilical cords where expanded MSCs were cryopreserved in human platelet lysate in vials (page 3, right col. para. 1). Smith teaches the MSCs are positive for CD73, CD90, CD105, and CD44 and negative for CD34, CD45, CD11b, CD19, and HLA-DRT (page 8, left col. last para.; Figure 5). Smith teaches surface marker expression between fresh and frozen and thawed MSCs showed no difference (page 12, left col. para. 1). Smith teaches clinical trials will require the freezing of cells for use because using fresh cells is not feasible given the rigorous quality control and release testing that must be done to determine if the cells meet the standards for clinical use (page 12, left col. para. 1).
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to combine the teachings of Patel regarding treating a respiratory condition with an isolated population of MSCs with the teachings of Xu regarding administering MSCs in PBS for treating acute lung injury with the teachings of Smith regarding cryopreserving MSCs in vials to arrive at the claimed composition comprising an isolated population of stem or progenitor cells in a first container; and a dilution buffer in a second container, wherein the isolated population of stem or progenitor cells express at least three cell markers selected from the group consisting of CD29, CD73, CD90, CD166, SSEA4, CD9, CD44, CD146, or CD105; and wherein the stem or progenitor cells do not express at least five cell markers selected from the group consisting of NANOG, CD45, CD34, CD14, CD79, CD106, CD86, CD80, CD19, CD117, Stro-1, or HLA-DR. One would have been motivated to combine the teachings in a composition to treat respiratory disorders as Patel teaches treating COPD with the cells improved lung function and Xu teaches MSCs are a potential therapy for ARDS and Smith teaches clinical trials will require the freezing of cells for use because using fresh cells is not feasible given the rigorous quality control and release testing that must be done to determine if the cells meet the standards for clinical use. One would have a reasonable expectation of success in combining the teachings as Xu teaches the MSCs in PBS reduced lung injury and Smith teaches cryopreservation of MSCs did not alter surface markers expression relative to fresh MSCs.
Maintained Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
22. Claims 19 and 21 remain rejected and claims 22 – 25 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 7 of U.S. Patent No. 9803176 (‘176) in view of Patel (WO-2013102219-A1; Filed 12/31/2012; Published 07/04/2013; previously cited), hereinafter Patel. Although maintained, note that the rejection is revised in view of Applicant’s amendments to claims 22 – 25 that now depend from claim 19 and are included in this rejection.
The instant claims and Patent claims 1 – 7 are directed to overlapping subject matter of isolated cells that express at least three cell markers selected from the group consisting of CD29, CD73, CD90, CD166, SSEA4, CD9, CD44, CD146, or CD105; and wherein the cells do not express at least five cell markers selected from the group consisting of NANOG, CD45, CD34, CD14, CD79, CD106, CD86, CD80, CD19, CD117, Stro-1, or HLA-DR where the isolated cells are capable of differentiation into chondrocytes, osteocytes, and cardiomyocytes. In the instant case, the claims are directed to a kit for treating a respiratory condition in a subject, comprising: an isolated population of stem or progenitor cells in a first container; and a dilution buffer in a second container, wherein the isolated population of stem or progenitor cells express at least three cell markers selected from the group consisting of CD29, CD73, CD90, CD166, SSEA4, CD9, CD44, CD146, or CD105; and wherein the stem or progenitor cells do not express at least five cell markers selected from the group consisting of NANOG, CD45, CD34, CD14, CD79, CD106, CD86, CD80, CD19, CD117, Stro-1, or HLA-DR. The dependent claims recite the kit is cryopreserved (claim 20) and that the progenitor cells include a cell type selected from the group consisting of adipocytes, chondrocytes, osteocytes, cardiomyocytes, endothelial cells, mesenchymal stem cells, and myocytes (claim 21 – 25).
Claim 1 of ‘176 recites an isolated cell wherein the isolated cell expresses at least three cell markers selected from the group consisting of CD29, CD73, CD90, CD166, SSEA4, CD9, CD44, CD146, or CD105; and wherein the stem or progenitor cells do not express NANOG and at least five cell markers selected from the group consisting of CD45, CD34, CD14, CD79, CD106, CD86, CD80, CD19, CD117, Stro-1, or HLA-DR. Claim 1 of ‘176 lacks the cells are in a container and a dilution buffer in a container of instant claim 19. Patel teaches administration of an isolated population of cells for treating COPD and teaches the cells express CD29, CD73, CD90, CD166, SSEA4, CD9, CD44, CD146, and CD105 and do not express CD45, CD34, CD14, CD79, CD106, CD86, CD80, CD19, CD117, Stro-1, and HLA-DR (page 4, lines 1 – 3; page 8, lines 18 – 34; page 14, lines 27 – 30; page 16, Example 2; page 17, Example 3 – 4; page 20 – 21, Example 9; Figures 3 – 4). Patel teaches in Table 3 that intravenous infusion and inhalation of the cells increases lung function as measured by comparing FEV1/FVC pre to FEV1/FVC post. Patel teaches cells can be delivered at various doses and the cell dosage range can be calculated based on the subject’s weight (page 13, lines 21 – 27; page 21, lines 8 – 9). It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to have included the cells of ‘176 in a container with dilution buffer in a second container to administer various doses of the cells to a person with COPD as taught by Patel in order to provide various cell doses.
Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
23. Claims 6 and 7 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.
24. Regarding claim 6, it is unclear if the claim is narrowing the scope of claim 1 regarding “a pathogenic infection” because although claim 6 does not recite some of the pathogenic infections recited in claim 1 (chickenpox, diphtheria, group A streptococcus, legionnaire’s disease, measles, and mumps), those that are excluded in claim 6 are viral or non-viral infections and claim 6 broadly recites that the pathogenic infection includes “viral infections” and “non-viral infections”.
25. Regarding claim 7, it is unclear if the claim is narrowing the scope of claim 1 regarding “a pathogenic infection” because although claim 7 does not recite some of the pathogenic infections recited in claim, those that are excluded in claim 7 are viral or non-viral infections and claim 7 broadly recites that the pathogenic infection includes “viral infections” and “non-viral infections”.
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.
26. Claim(s) 1 – 4, 6 – 8, and 14 – 17 is/are rejected under 35 U.S.C. 103 as being unpatentable over Matthay (Matthay MA, et. al. Lancet Respir Med. 2019 Feb;7(2):154-162), hereinafter Matthay as evidenced by McAuley (McAuley, D. F., et al. American Journal of Physiology-Lung Cellular and Molecular Physiology 306.9 (2014): L809-L815.), hereinafter McAuley in view of Curley (Curley, Gerard F., et al. Critical care medicine 45.2 (2017): e202-e212.), hereinafter Curley as evidenced by Kouroupis (Kouroupis, D., et al. Eur Rev Med Pharmacol Sci 25.12 (2021): 4435-4438.), hereinafter Kouroupis.
Regarding claim 1 and 6 – 8, Matthay teaches a method of infusing allogeneic mesenchymal stem cells (MSCs) into patients with ARDS (“infusing a composition comprising autologous or allogeneic stem or progenitor cells to a subject having a respiratory condition” of claim 1) caused by pneumonia (“respiratory condition is initiated as a result of a pathogenic infection” of claim 1 and “ARDS” of claim 1 and 6 – 8) (page 4, para. 2; Table 1). Matthay teaches the MSCs are infused at a dose of 10 x 106 MSC/kg predicted bodyweight (page 3, last para.; page 7, last para.; page 9, para. 3) but does not teach “an increase in a serum level of soluble TNFR2” of claim 1.
Regarding “the stem or progenitor cells express at least three cell markers” and “the stem or progenitor cells do not express at least five cell markers” of claim 1, Matthay teaches the allogeneic MSCs were derived from human bone marrow and were prepared with support from the NHLBI Production Assistance for Cellular Therapies Program at the University of Minnesota (Minneapolis, MN) and were tested by flow cytometry for CD105, CD73, CD90, CD45, CD34, CD14, CD19, and HLA-DR (page 4, para. 2) but does not teach the expression of each. Allogeneic bone marrow-derived human MSCs manufactured at Molecular and Cellular Therapeutics of the University of Minnesota are analyzed by flow cytometry to characterize the cell types in the final product where the cells are positive for CD73, CD90, and CD105 (“the stem or progenitor cells express at least three cell markers”) and negative for CD14, CD19, CD34, CD45, and HLA-DR (“the stem or progenitor cells do not express at least five cell markers”) as evidenced by McAuley (page L810, left col. para. 6).
Regarding “intravenously” of claims 2 – 4, Matthay teaches the MSCs were administered intravenously (page 9, para. 3).
Regarding “mesenchymal stem cells” of claims 14 and 15, Matthay teaches the cells are mesenchymal stem cells (page 4, para. 2).
Matthay teaches the MSCs are infused at a dose of 10 x 106 MSC/kg predicted bodyweight, which is the same as 1 x 107 (page 3, last para.; page 7, last para.; page 9, para. 3) but does not teach “an increase in a serum level of soluble TNFR2” of claim 1 or the progenitor cells are chondrocyte progenitor cells of claim 16 or the progenitor cells are osteocyte progenitor cells of claim 17. However, Matthay teaches in several preclinical studies using animal models of ARDS, treatment with MSCs derived from bone marrow, umbilical cord, or adipose tissue has reduced the severity of acute lung injury from infectious causes (page 2, last para.). Matthay teaches MSC viability after thawing was found to be variable and more research is needed to optimize the methods of MSC cryopreservation, thawing, and production of MSCs for clinical trials (page 5, last para.; page 7, para. 4; page 8, para. 4; page 9, para. 2). Matthay teaches a decrease of concentrations of angiopoietin 2 in plasma was significantly greater in the MSC infusion group compared to the placebo group but teaches no change in IL-6 levels (page 7, para. 3; page 8, para. 3). Matthay teaches the reductions in angiopoietin-2 concentrations might have been related to the release of anti-inflammatory factors that can moderate lung injury (page 8, para. 3). Matthay teaches no MSC-related predefined hemodynamic or respiratory adverse events within 6 hours of the start of the infusion in patients with moderate to severe ARDS (page 7, last para.). Matthay teaches a limitation of their trial was that the sample size was too small to reliably assess efficacy and larger trials are needed to assess efficacy and the viability of MSCs must be improved (page 2, para. 3; page 9, last para.). Matthay teaches ARDS occurred in 10% of patients admitted to intensive-care units, and mortality among these patients was increased by more than 30% despite improvement in supportive care and ventilator management (page 2, para. 1).
Regarding “an increase in a serum level of soluble TNFR2” of claim 1, Curley teaches administering 1x107 human umbilical cord MSCs (UC-MSCs)/kg intravenously to rats with E.coli-induced ARDS reduced TNF-α and IL-6 in bronchial alveolar lavage fluid (page e204, right col. para. 2; page e205, right col. para. 4; Figure 4B and C). UC-MSCs administered to virally-induced ARDS patients reduce plasma levels of TNFα and TNFβ and increase sTNFR2 as evidenced by Kouroupis (page 4436, right col. para. 2; Figure 1). Curley teaches UC-MSCs are comparable to bone-marrow derived MSCs in treating E.coli-induced ARDS (page e203, left col. para. 1 and right col. last para.; page e204, right col. para. 2; page e205, left col. para. 2). Curley teaches the UC-MSCs are positive for CD73, CD90, CD105, and CD146 are negative for HLA-DR, CD45 and CD34 in Supplementary Figure 2 (page e204, right col. last para.). Curley teaches the mechanisms of action of MSCs in ARDS are diverse and include the secretion of paracrine mediators that reduce injury and inflammation and enhance cellular repair (page e203, left col. para. 1).
Regarding “chondrocyte progenitor cells” of claim 16 and “osteocyte progenitor cells” of claim 17, Curley teaches the MSCs have osteogenic and chondrogenic differentiation potential (page e204, right col. last para.).
Curley teaches the scale-up of bone marrow MSC manufacturing required for phase III clinical trials necessitates large-scale expansion and proliferation from each volunteer bone marrow donor to generate sufficient therapeutic product and aspirating bone marrow from a patient is an invasive procedure (page e203, left col. para. 3; page e205, right col. last para.). Curley teaches the phenotype of culture-expanded MSCs can be altered during extensive culture expansion and this may play a role in modifying their regenerative and immune suppressive properties (page e203, left col. para. 3). Curley teaches UC-MSCs present some advantages over other stem cell tissue sources particularly in regard to the need for extensive culture expansion (page e203, left col. para. 3). Curley teaches a UC is a plentiful, easily assessable biologic waste product and a single UC produces 10 times more early passage MSCs than a bone marrow harvest, allowing generation of high numbers of early passage MSCs (page e203, left col. para. 3). Curley teaches all UC-MSCs are the same “age” thus reducing variability and potentially enhancing potency (page e203, left col. para. 3). Curley teaches the UC-MSCs are effective in a clinically relevant model of pneumonia-induced ARDS producing beneficial effects on oxygenation, respiratory static compliance, and inflammatory cell infiltration and these results are comparable to bone marrow MSCs, and may have therapeutic potential for human ARDS (page e205, right col. para. 2; page e208, right col. para. 2; page e209, left col. and right col. last para.). Curley teaches UC may represent an attractive tissue source of MSCs for lung injury and UC-MSCs can be collected at no risk to the donor, have low immunoreactivity, and have low inherent pathogen transmission (page e205, right col. last para.). Curley teaches the procedure for preparation of UC-MSCs offers novel and effective methods for preparing MSCs for research and clinical trials in ARDS as the UC-MSCs were prepared (thawed prior to the administration in serum-free conditions) and administered (systemically, after establishment of injury) as in a clinical trial (page e208, right col.). Curley teaches MSCs represent a promising strategy for ARDS and MSCs reduce mortality, improve alveolar epithelial barrier function, and attenuate inflammation and lung injury in diverse preclinical ARDS animal models (page e203, left col. para. 1).
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to combine the teachings of Matthay regarding a method of treating ARDS by infusing allogeneic bone marrow MSCs to pneumonia-induced ARDS subjects with the teachings of Curley regarding a method of treating ARDS by infusing umbilical cord MSCs to pneumonia-induced ARDS subjects to arrive at the claimed method of treating a respiratory condition in a subject, comprising: infusing a composition comprising autologous or allogeneic stem or progenitor cells to a subject having a respiratory condition, wherein the stem or progenitor cells express at least three cell markers selected from the group consisting of CD29, CD73, CD90, CD166, SSEA4, CD9, CD44, CD146, or CD105; wherein the stem or progenitor cells do not express at least five cell markers selected from the group consisting of NANOG, CD45, CD34, CD14, CD79, CD106, CD86, CD80, CD19, CD117, Stro-1, or HLA-DR; wherein the respiratory condition is initiated as a result of a pathogenic infection including chickenpox, coronavirus infections, viral infections, non-viral infections, diphtheria, group A streptococcus, haemophilus influenzae type b, influenza, legionnaires' disease, measles, Middle East Respiratory Syndrome (MERS), mumps, pneumonia, pneumococcal meningitis, rubella, Severe Acute Respiratory Syndrome (SARS), tuberculosis, whooping cough, or Acute Respiratory Distress Syndrome (ARDS), or a combination thereof; and wherein the stem or progenitor cells are infused in a therapeutically effective amount to increase a serum level of soluble TNFR2 in the subject to decrease a serum level of TNFα or TNFβ in the subject. One would have been motivated to combine the teachings of Matthay and Curley in a clinical trial of treating ARDS with umbilical cord-MSCs as Matthay teaches ARDS occurred in 10% of patients admitted to intensive-care units, and mortality among these patients was increased by more than 30% despite improvement in supportive care and ventilator management and Matthay teaches a limitation of their trial was that the sample size was too small to reliably assess efficacy and larger trials are needed to assess efficacy and the viability of MSCs must be improved and Curley teaches UC-MSCs present some advantages over other stem cell tissue sources particularly in regard to the need for extensive culture expansion and Curley teaches all UC-MSCs are the same “age” thus reducing variability and potentially enhancing potency. One would have a reasonable expectation of success in combining the teachings as Matthay teaches in several preclinical studies using animal models of ARDS, treatment with MSCs derived from bone marrow and umbilical cord has reduced the severity of acute lung injury from infectious causes and Curley teaches a UC is a plentiful, easily assessable biologic waste product and a single UC produces 10 times more early passage MSCs than a bone marrow harvest, allowing generation of high numbers of early passage MSCs and Curley teaches UC-MSCs are comparable to bone-marrow derived MSCs in treating E.coli-induced ARDS and Curley teaches the UC-MSCs reduced TNF-α and IL-6.
27. Claim(s) 9 – 13 and 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Matthay (Matthay MA, et. al. Lancet Respir Med. 2019 Feb;7(2):154-162), hereinafter Matthay as evidenced by McAuley (McAuley, D. F., et al. American Journal of Physiology-Lung Cellular and Molecular Physiology 306.9 (2014): L809-L815.), hereinafter McAuley in view of Curley (Curley, Gerard F., et al. Critical care medicine 45.2 (2017): e202-e212.), hereinafter Curley as evidenced by Kouroupis (Kouroupis, D., et al. Eur Rev Med Pharmacol Sci 25.12 (2021): 4435-4438.), hereinafter Kouroupis as applied to claims 1 – 4, 6 – 8, and 14 – 17 above, and further in view of Patel (WO-2013102219-A1; Filed 12/31/2012; Published 07/04/2013; previously cited) hereinafter Patel.
Matthay in view of Curley make obvious the limitations of claim 1 as set forth above. Matthay (page 4, para. 2) as evidenced by McAuley (page L810, left col. para. 6) teaches the MSCs are positive for CD73, CD90, and CD105 and negative for CD14, CD19, CD34, CD45, and HLA-DR but does not teach the MSCs are also positive for CD29, CD166, SSEA4, CD9, CD44, and CD146 of claim 9 or are also negative for CD79, CD106, CD86, CD80, CD117, and Stro-1 of claim 10 or the cells are positive for SOX2 of claim 11 or the cells are positive for OCT4 of claim 12 or the cells are positive for SOX2 and OCT4 of claim 13. Curley teaches the MSCs are chondrocyte and osteocyte progenitor cells but does not teach the MSCs are cardiomyocyte progenitor cells of claim 18.
Regarding claims 9 – 13, Patel teaches umbilical cord MSCs (UC-MSCs) that are positive for CD29, CD166, SSEA4, CD9, CD44, and CD146 (claim 9) and negative for CD79, CD106, CD86, CD80, CD117, and Stro-1 (claim 10) and also express SOX2 and OCT4 (claims 11 – 13) that in Example 9 are used to treat a respiratory disorder that is COPD at a dose of 50 x 106 – 400 x 106 where the cells are administered intravenously or inhaled or both intravenously and inhaled (page 8, lines 26 – 27 and 32 – 34; Figure 3 and 4; page 10, lines 29 – 31; page 20, lines 10 – 28; page 21, lines 1 – 25; Table 3). Patel teaches in Table 3 that the MSCs improved lung function as determined by an increase in FEV1/FVC.
Regarding claim 18, Patel teaches the umbilical cord MSCs are capable of differentiation into cardiomyocytes, chondrocytes, and osteocytes and other cell types (page 2, lines 3 – 20; Figure 8 – 10; page 8, lines 1 – 6; page 12, lines 30 – 34; page 13, lines 1 – 20).
Patel teaches methods for isolating and culturing the UC-MSCs where 500,000 – 1,000,000 cells can be harvested and further expanded (page 16, lines 40 – 43; page 17, lines 1 – 2). Patel teaches a method of passaging the cells for clinical use (page 17, lines 4 – 30).
It would have been obvious prior to the effective filing date of the invention as claimed for the person of ordinary skill in the art to combine the teachings of Matthay regarding a method of treating ARDS by infusing allogeneic bone marrow MSCs to pneumonia-induced ARDS subjects with the teachings of Curley regarding a method of treating ARDS by infusing umbilical cord MSCs to pneumonia-induced ARDS subjects with the teachings of Patel regarding umbilical cord MSCs for treating a respiratory disorder that can be passaged for clinical use to arrive at the claimed method where the cells are positive for CD29, CD73, CD90, CD166, SSEA4, CD9, CD44, CD146, CD105, SOX2, and OCT4 and negative for NANOG, CD45, CD34, CD14, CD79, CD106, CD86, CD80, CD19, CD117, Stro-1, and HLA-DR; and are cardiomyocyte progenitor cells. One would have been motivated to combine the teachings of Matthay, Curley, and Patel in a clinical trial of treating ARDS with umbilical cord-MSCs as Matthay teaches ARDS occurred in 10% of patients admitted to intensive-care units, and mortality among these patients was increased by more than 30% despite improvement in supportive care and ventilator management and Curley teaches UC is a plentiful, easily assessable biologic waste product and a single UC produces 10 times more early passage MSCs than a bone marrow harvest, allowing generation of high numbers of early passage MSCs and Patel teaches the UC-MSCs can be used to treat a respiratory disorder and Patel teaches methods for expansion and passaging UC-MSCs for clinical use. One would have a reasonable expectation of success in combining the teachings as Matthay teaches in several preclinical studies using animal models of ARDS, treatment with MSCs derived from bone marrow and umbilical cord has reduced the severity of acute lung injury from infectious causes and Curley teaches UC-MSCs are comparable to bone-marrow derived MSCs in treating E.coli-induced ARDS and Patel teaches the UC-MSCs improved lung function.
Applicant’s Arguments/ Response to Arguments
28. Applicant Argues: On page 6, para. 8, Applicant asserts that the claims have been amended in the way suggested by the Examiner.
Response to Argument: In response, amended claim 2 still recites “further” and therefore the objection to claim 2 is maintained.
Applicant Argues: On page 9 – 11, Applicant traverses the rejection of the claims under 112(a). Applicant asserts that the amendments to claim 1 narrow the breadth in that the cells are not xenogeneic and the respiratory condition is initiated as a result of a pathogenic infection, and the dosage has been limited to a therapeutically effective amount to increase a serum level of sTNFR2.
Response to Argument: This is not found persuasive because the working example provided in Applicant’s specification of COVID-19 patients with ARDS is much narrower than the claimed breadth of any respiratory condition initiated as a result of any pathogenic infection. As Applicant states, the dosage and most effective route of infusion would be different for different patients and for different respiratory conditions (Applicant’s remarks at page 10, para. 1 – 2), which underscores the unpredictability of the claimed breadth of respiratory conditions in view of the single working example for ARDS and the previously cited unpredictability in the prior art and thus undue experimentation would be required to practice the invention.
Applicant Argues: On page 13, para. 3 – 4, Applicant asserts that Patel does not anticipate the amended claims.
Response to Argument: The previous rejection of the claims as being anticipated by Patel have been withdrawn in view of Applicant’s amendment to the claims.
Applicant Argues: On page 14, Applicant asserts that a person of ordinary skill in the art would not have a reasonable expectation of success in combining Patel with Cardenes.
Response to Argument: The previous rejection of the claims using the teachings of Cardenes has been withdrawn in view of Applicant’s amendment to narrow the scope of the claim 1 to autologous or allogeneic stem or progenitor cells. New rejections necessitated by the claim amendments are set forth above.
Applicant Argues: On page 15, para. 1 – 3, Applicant asserts that a person or ordinary skill in the art would not have a reasonable expectation of success in combining the references in the way suggested because the cells of Patel are different from Xu and Smith. Applicant asserts that Xu does not actually teach that the stem cells used by Xu can be used to treat ARDS.
Response to Argument: This is not found persuasive because Patel, Xu, and Smith all teach MSCs and their use in treating respiratory diseases. The claims broadly recite “stem or progenitor cells” that express at least three cell markers selected from the recited group and that do not express at least five cell markers from the recited group and each of the cells of Patel, Xu, and Smith meet these limitations. Further, the claims broadly recite “a respiratory condition” as an intended use of the cells for treating any respiratory condition and the cells of Patel and Smith and the cells of Xu are used to treat a respiratory condition.
Applicant Argues: On page 15, last para. and page 16, Applicant asserts that the instant claims are patentably distinct from the claims of U.S. Patent No. 9,803,176.
Response to Argument: This is not found persuasive because a person of ordinary skill in the art would conclude that the invention of instant claims 19 and 21 – 25 would have been an obvious variation of the isolated cells of U.S. Patent No. 9,803,176 because Patel teaches administration of an isolated population of cells for treating COPD and teaches the cells express CD29, CD73, CD90, CD166, SSEA4, CD9, CD44, CD146, and CD105 and do not express CD45, CD34, CD14, CD79, CD106, CD86, CD80, CD19, CD117, Stro-1, and HLA-DR where the cells improve lung function (page 4, lines 1 – 3; page 8, lines 18 – 34; page 14, lines 27 – 30; page 16, Example 2; page 17, Example 3 – 4; page 20 – 21, Example 9; Figures 3 – 4).
Conclusion
No claims allowed.
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 ZANNA M BEHARRY whose telephone number is (571)270-0411. The examiner can normally be reached Monday - Friday 8:45 am - 5:45 pm.
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, Peter Paras can be reached at (571)272-4517. 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.
/Z.M.B./Examiner, Art Unit 1632
/MARCIA S NOBLE/Primary Examiner, Art Unit 1632