Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Priority
This application is a CON of 16/889,354 06/01/2020 ABN which is a CON of 16/036,402 07/16/2018 PAT 10,688,134 which is a CON of 14/650,171 06/05/2015 PAT 10,028,979 which is a 371 of PCT/AU2013/001454 12/12/2013 which claims benefit of 61/736,352 12/12/2012.
Claim Status
Claims 1 and 12-22 are currently amended, claims 2-11 and 23-25 have been cancelled, claims 1 and 12-22 have been considered on their merits.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of pre-AIA 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 1, 12-13, 16-18, and 20-21 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Bonfield et al. (AJP-Lung Cell Mol Physiol 299, 2010, IDS ref.).
Regarding claim 1, Bonfield et al. teach Human mesenchymal stem cells suppress chronic airway inflammation in the murine ovalbumin asthma model (Abstract). Bonfield et al. teach the pathogenic characteristics of allergic asthma are associated with airway inflammation and infiltration of mast cells, basophils, eosinophils, monocytes, and T helper type 2 lymphocytes along with the production of isotype-specific IgE (IgE-mediated allergy) (p. L760, 1st column). Bonfield et al. teach the phenotype of the hMSCs was defined by evaluating 100 markers using fluorescent activated cell sorting (FACS), wherein the absence of CD34 and CD45 and the presence of SH2 (CD105), SH3/SH4 (CD73), cell surface protein Stro-1, and others were used to identify hMSCs (population of cells enriched for Stro-1) (p. L761, MSCs). Bonfield et al. teach hMSCs were harvested during log-growth at passage 2 and given in a single intravenous tail vein injection of 1 x 106 cells in 100 µl of sterile saline (p. L761, MSCs). Bonfield et al. teach animals sensitized with ovalbumin and challenged with ovalbumin followed by hMSC therapy had significantly less IgE relative to the ovalbumin challenged mice not treated with hMSCs (p. L764, 1st column).
Regarding claims 12, 13, and 17, Bonfield et al. teach hMSCs were harvested during log-growth at passage 2 and given in a single intravenous (claim 13) tail vein injection of 1 x 106 cells (claim 17) in 100 µl of sterile saline (p. L761, MSCs). Intravenous injection reads as systemically administered (claim 12).
Regarding claim 16, the limitations following “sufficient to achieve” is interpreted as intended results of the method of claim 1. Intended results are not given weight when it simply expresses the intended result of a process step positively recited. Since Bonfield et al. teach all of the steps of the method of claim 1, the intended results would necessarily occur.
Even if these limitations were considered limiting, Bonfield et al. teach the pathogenic characteristics of allergic asthma are associated with airway inflammation and infiltration of mast cells, basophils, eosinophils, monocytes, and T helper type 2 lymphocytes along with the production of isotype-specific IgE (p. L760, 1st column). Bonfield et al. teach the specificity of the hMSC response was studied by evaluating bronchoalveolar lavage (BAL) from ovalbumin-challenged mice, wherein, treatment with hMSCs resulted in decreased total cell count (pp. L762-L763, Fig. 3A). Bonfield et al. teach the differential showed a decrease in eosinophils and macrophages with an increase in neutrophils over the chronic response without hMSCs (p. L763, 1st column). Bonfield et al. teach histologically, hMSC treatment resulted in a dramatic decrease in airway inflammation, goblet cell hyperplasia, and epithelial cell lining thickening (p. L763, 1st column).
Regarding claim 18, the claim and the instant specification do not limit the quantity of cells in said “whole body dose”, therefore, the claim is interpreted as any therapeutically effective quantity of cells. Since Bonfield et al. teach animals challenged with ovalbumin followed by hMSC therapy had significantly less IgE relative to the ovalbumin challenged mice not treated with hMSCs, the Stro-1+ cell delivery is considered a whole body dose.
Regarding claim 20, the hMSCs of Bonfield et al. would be considered allogeneic, as the subject is a different species.
Regarding claim 21, Bonfield et al. teach hMSCs were harvested during log-growth at passage 2 (culture expanded) (p. L761, MSCs).
Thus, the reference anticipates the subject matter of claims 1, 12-13, 16-18, and 20-21.
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 pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter 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 pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 14-15 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Bonfield et al. (AJP-Lung Cell Mol Physiol 299, 2010, IDS ref.) as applied to claims 1, 12-13, 16-18, and 20-21 above, and further in view of D’Agostino et al. (Expert Opin. Biol. Ther., 2010) as evidenced by Sundin et al. (Future Cardiol., 2023) and Singh et al. (Monaldi Arch Chest Dis, 2010).
Bonfield et al. anticipate the subject matter of claims 1, 12-13, 16-18, and 20-21, thus also render them obvious.
Regarding claim 14, Bonfield et al. do not teach administration a plurality of times. However, administration of cells multiple times for treatment in human subjects is known in the art.
D’Agostino et al. teach the use of MSCs for COPD treatment is ongoing to establish the safety and efficacy of multiple administration of allogeneic MSCs, Prochymal®, in patients with moderate and severe COPD (p. 684, 1st column). This suggests administration a plurality of times would be effective for treatment of chronic, obstructive lung diseases causing wheezing and breathlessness. Prochymal®, is known in the art to be STRO-1+ cells, as evidenced by Sundin et al., who teach an MSC cultured cell product named rexlemestrocel-L (REX-L), previously known as Prochymal®, and are selected from a subgroup of bone marrow cells that are both STRO-1 and STRO-3 positive (p. 568, Mesoblast allogeneic bone marrow-derived mesenchymal precursor cells).
Therefore, it would have been obvious to one of ordinary skill in the art to administer the cells of Bonfield et al. a plurality of times as taught by D’Agostino et al. with a reasonable expectation of success because D’Agostino et al. teach multiple administration of allogeneic MSCs for the treatment of human patients with a pulmonary disease. One would be motivated to administer the cells of Bonfield et al. a plurality of times as taught by D’Agostino et al. because Bonfield et al. is conducting a proof of concept utilizing a mouse model and administration to a human patient suffering from a pulmonary disease would likely require repeated administration due to the chronic nature of the disease. While COPD is not an IgE mediated allergic reaction, COPD is associated with elevated IgE serum levels, as evidenced by Singh et al. (Abstract). Additionally, D’Agostino et al. suggest MSCs can potentially be used for COPD, or other lung diseases (p. 634, Section 6).
Regarding claim 15, Bonfield et al. in view of D’Agostino et al. teach administering multiple doses of cells to patients with a subject with having difficulty breathing. Specifically, D’Agostino et al. teach the use of MSCs for COPD treatment is ongoing to establish the safety and efficacy of multiple administration of allogeneic MSCs in patients with moderate and severe COPD (p. 684, 1st column). D’Agostino et al. teach patients with COPD suffer from pulmonary inflammation and dyspnea, which reads as difficulty breathing. Since a patient with COPD would have chronic difficulty breathing, this reads on further administration of cells following a subject having difficulty breathing (claim 15 (i)).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim 19 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Bonfield et al. (AJP-Lung Cell Mol Physiol 299, 2010, IDS ref.) as evidenced by Hare et al. (J Am Coll Cardiol, 2009).
Bonfield et al. anticipate the subject matter of claims 1, 12-13, 16-18, and 20-21, thus also render them obvious.
Regarding claim 19, Bonfield et al. teach administering 1 x 106 cells in 100 µl of sterile saline, when converted to a 10 mL solution, the number of cells would be 1 x 108 (100 x 106). Bonfield et al. do not teach administering 150 x 106 cells.
However, a prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. See M.P.E.P. § 2144.05(I). Furthermore, number of cells administered would have been a routine matter of optimization on the part of the artisan of ordinary skill, said artisan recognizing the quantity of cells would depend on the subject being treated and Bonfield et al. is treating mice, while a greater quantity of cells may be required for a human subject. A holding of obviousness over the cited claims is therefore clearly required. The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed range is the optimum dose. See Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382.; See also M.P.E.P. § 2144.05 (II)(A).
Additionally, Hare et al. demonstrate in a treatment of subjects with Prochymal infusions cohorts of 0.5, 1.6, and 5.0 x 106 hMSCs/kg body weight to human subjects (p. 3, Treatment groups and infusion parameters). Hare et al. teach there was no evidence of increased toxicity with the administration of hMSCs compared with placebo, and administration was well tolerated at all cell dose levels (p. 6, AEs), which is approximately 3.5 x 108 cells for a typical human subject weighing 70 kg, at a dosage of 5.0×106 hMSCs/kg, which demonstrates the wide range of acceptable cell number for treatment in a human subject.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim 22 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Bonfield et al. (AJP-Lung Cell Mol Physiol 299, 2010, IDS ref.) as applied to claims 1, 12-13, 16-18, and 20-21 above, and further in view of Gronthos et al. (Stem Cells and Development, 2007, IDS ref.).
Bonfield et al. anticipate the subject matter of claims 1, 12-13, 16-18, and 20-21, thus also render them obvious.
Regarding claim 22, Bonfield et al. is silent to the STRO-1+ cells are STRO-1bri or express tissue non-specific alkaline phosphatase (TNAP). The instant specification teaches TNAP is known as STRO-3. The STRO-3 marker is known in the art as a tissue-nonspecific alkaline phosphatase (TNAP), which selects a more refined and homogenous population of highly potent multipotent colony-forming unit fibroblasts (CFU-Fs) within the broader STRO-1bright stromal cell population.
Gronthos et al. teach STRO-3, that identifies a subset of STRO-1+ marrow cells able
to isolate a high proportion of BMSSCs in human BM that lack phenotypic characteristics of leukocytes (p. 954, Introduction). Gronthos et al. teach STRO-3 was found to identify a unique epitope expressed on the extracellular domain of tissue nonspecific alkaline phosphatase
(TNSALP) (p. 954, Introduction). Gronthos et al. teach selection of the STRO-1bright/STRO-3+ fraction resulted in a more that 410-fold enrichment of CFU-F relative to their incidence in unseparated BMMNCs samples prior to MACS/FACS separation and compared to STRO-1+/STRO-3- cells which only contained a few CFU-F (p. 960, 1st column), which suggests STRO-1bright/STRO-3+ cells would be a superior choice over STRO-1+/STRO-3- cells.
Therefore, it would have been obvious to one of ordinary skill in the art to utilize the STRO-1bright/STRO-3+ cells taught by Gronthos et al. in the method of Bonfield et al. with a reasonable expectation of success because Gronthos et al. teach a consistent feature of marrow CFU-F-derived colonies of virtually all species examined is their considerable heterogeneity in terms of size, morphology, enzyme histochemistry, proliferation and developmental potential (p. 954, Introduction). One would be motivated to utilize the STRO-1bright/STRO-3+ cells taught by Gronthos et al. in the method of Bonfield et al. because the characteristics of the STRO-1bright/STRO-3+ cells would suggest a more effective enriched population for the purpose of tissue repair based on the elevated CFU-F.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
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.
Claims 1 and 12-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 10,028,979.
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims render obvious the instant claims.
Regarding claim 1, patented claims 5, 12, and 22 all depend from patented claim 1, which disclose a method of treating a respiratory condition in a subject comprising administering cells enriched for STRO-1bright. STRO-1bright cells read as a population of cells enriched for STRO-1+ cells. Patented claim 5 disclose where the respiratory condition is asthma, which can be extrinsic or atopic asthma, which are IgE-mediated. Patented claim 12 disclose where the respiratory condition is allergy to house dust mite allergen (HDM), which is a IgE-mediated allergy. Patented claim 22 discloses the respiratory condition is IgE-mediated allergy. Therefore at least patented claims 1, 5, 12, and 22 read on instant claim 1.
Regarding claim 12, patented claim 13 discloses the population of enriched cells are administered systematically.
Regarding claim 13, patented claim 14 discloses the population of enriched cells are administered intravenously or intranasally.
Regarding claim 14, patented claim 15 discloses the population of enriched cells are administered a plurality of times.
Regarding claims 15 and 16, patented claims 16 and 17, respectively, are identical to instant claims 15 and 16.
Regarding claim 17, patented claim 18 discloses administering between 1x106 to 150x106 STRO-1 cells.
Regarding claim 18, patented claim 19 discloses administering a whole body dose of STRO-1 cells.
Regarding claim 19, patented claim 20 discloses administering 150x106 STRO-1 cells in 10 mL to the subject.
Regarding claim 20, patented claim 21 discloses the population of STRO-1 cells are allogeneic.
Regarding claim 21, the patented claims do not disclose culture expansion prior to administration, however, it is well known in the art cells are cultured and expanded in order to achieve a pure culture of cells in sufficient quantity for administration.
Regarding claim 22, patented claim 1 disclose the cells are STRO-1bright.
Claims 1 and 12-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 10,688,134 in view of Gronthos et al. (Stem Cells and Development, 2007, IDS ref.).
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims render obvious the instant claims.
Regarding claim 1, patented claims 5 and 10 depend from patented claim 1, which disclose a method of treating a respiratory condition in a subject comprising administering cells enriched for STRO-1+. Patented claim 5 disclose where the respiratory condition is asthma, which can be extrinsic or atopic asthma, which are IgE-mediated. Patented claim 10 disclose where the respiratory condition is allergy to house dust mite allergen (HDM), which is a IgE-mediated allergy. Therefore at least patented claims 1, 5, and 10 read on instant claim 1.
Regarding claims 12-17, patented claims 11-16, respectively, are identical to instant claims 12-17.
Regarding claim 18, the claim and the instant specification do not limit the quantity of cells in said “whole body dose”, therefore, the claim is interpreted as any therapeutically effective quantity of cells. Therefore, patented claim 16 discloses administering 1x106 to 150x106 STRO-1 cells, which reads as a whole body dose.
Regarding claim 19, patented claim 18 is identical to instant claim 19.
Regarding claim 20, patented claim 19 discloses wherein the population is an allogenic population.
Regarding claim 21, patented claim 17 discloses the population has been culture expanded prior to administration.
Regarding claim 22, the patented claims do not disclose wherein the cells are STRO-1bri. However, Gronthos et al. teach STRO-3, that identifies a subset of STRO-1+ marrow cells able
to isolate a high proportion of BMSSCs in human BM that lack phenotypic characteristics of leukocytes (p. 954, Introduction). Gronthos et al. teach selection of the STRO-1bright/STRO-3+ fraction resulted in a more that 410-fold enrichment of CFU-F relative to their incidence in unseparated BMMNCs samples prior to MACS/FACS separation and compared to STRO-1+/STRO-3- cells which only contained a few CFU-F (p. 960, 1st column), which suggests STRO-1bright/STRO-3+ cells would be a superior choice over STRO-1+/STRO-3- cells.
Therefore, it would have been obvious to one of ordinary skill in the art to utilize the STRO-1bright/STRO-3+ cells taught by Gronthos et al. in the method of the patented claims with a reasonable expectation of success because Gronthos et al. teach a consistent feature of marrow CFU-F-derived colonies of virtually all species examined is their considerable heterogeneity in terms of size, morphology, enzyme histochemistry, proliferation and developmental potential (p. 954, Introduction). One would be motivated to utilize the STRO-1bright/STRO-3+ cells taught by Gronthos et al. in the method of the patented claims because the characteristics of the STRO-1bright/STRO-3+ cells would suggest a more effective enriched population for the purpose of tissue repair based on the elevated CFU-F.
Therefore, patented claim 1 in view of Gronthos et al. are obvious over instant claim 22.
Relevant prior art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Mohapatra et al. (WO 2009/042173 A1, published 02 April 2009)
Mohapatra et al. teach the utilization of bone-marrow derived stem cells in the treatment of allergic and inflammatory diseases, such as asthma.
Jones et al. (Chest, July 2011)
Jones et al. teach recent studies using bone marrow progenitor cells as stem cell therapies in the context of pulmonary hypertension, COPD, and asthma. Jones et al. teach in terms of respiratory disease, there is one trial in which ex vivo cultured adult human MSCs (Prochymal) are being administrated by IV infusion to patients with COPD with the aim of delaying disease progression by reducing lung inflammation in these patients.
Conclusion
No claims are allowed.
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/N.A.H./Examiner, Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631