DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 1-2,4-6,8-9,12-14,16-20, and 22 are under examination.
The former rejections are withdrawn because of the recent claim amendments. New rejections are put forward to address the newly added claim limitations. The examiner has considered all of applicants arguments and amendments. The references that are still being applied in the rejections below will be addressed directly below the rejection for convenience purposes.
Claim Objections
Claim 1 is objected to because of the following informalities: The claim recites that the apoptotic cells comprise a cell population in which the cells are less than 15% PI positive. PI is an abbreviation for propidium iodide and claim 1 needs to recite what PI stands for in the claim language. Appropriate correction is required.
Claim 6 is objected to because of the following informalities: “a toe joint, or a thumb joint” should instead be –a toe joint, a thumb joint--. Appropriate correction is required.
Claim 19 is objected to because of the following informalities: “multiple administration” should be –multiple administrations--. Claim 19 is further objected to because “week administrations” should be –weekly administrations--.
Claim 20 is objected to because “the dose” should be –a dose--.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2,4,8-9,12-20, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Saint-Remy (US 20150125880 in view of Mevorach (US 20180104277).
Saint-Remy teaches administering immature antigen presenting cells/mononuclear (apoptotic cells) into an animal (Paragraph 16-17,29,31,39,41, and 44) to treat an inflammatory condition such as osteoarthritis (Paragraph 70 of Saint-Remy). Saint-Remy teaches that apoptotic cells can be used to treat osteoarthritis and other inflammatory conditions (Paragraph 70 of Saint-Remy). Saint-Remy does not state that the apoptotic cells are in an “early apoptotic state” comprising more than 40% Annexin V positive and less than 15% PI positive cells (which are both characteristics of cells in the early apoptotic state). Nor does Saint-Remy discuss that their cells are irradiated prior to use.
Mevorach teaches that mononuclear cells in an early apoptotic state can be used to treat inflammatory/autoimmune conditions (Abstract and Paragraph 2 of Mevorach) and arthritis in general (Paragraphs 30 and 288 of Mevorach). The early apoptotic population of cells are at least 85% Annexin V positive and less than 10% of these cells stain positive for propidium iodide (PI) (Paragraph 110 of Mevorach). The cell population of Mevorach can be irradiated (Paragraph 18 of Mevorach). It would have been obvious to an artisan of ordinary skill at the time of effective filing to have used Mevorach’s early apoptotic mononuclear cells to treat osteoarthritis. An artisan would have been motivated to have used the cells in an early apoptotic state to treat arthritis because Mevorach’s mononuclear cells in an early apoptotic state can also treat autoimmune and/or inflammatory conditions (Abstract, Paragraph 2 of Mevorach) including arthritis in general (Paragraphs 30 and 288 of Mevorach). These paragraphs in Mevorach do not limit the arthritis to specific types of arthritis. Therefore, an artisan would have been motivated to have tried the early apoptotic cells of Mevorach to treat osteoarthritis since they are known to be able to treat generalized forms of arthritis and Mevorach’s early apoptotic cells can treat autoimmune/inflammatory conditions. Osteoarthritis qualifies as an autoimmune/inflammatory condition. There would be a high expectation for success using early apoptotic state cells in the process of Saint-Remy because Mevorach teaches that mononuclear cells in an early apoptotic state are capable of treating autoimmune/inflammatory conditions (Abstract, Paragraph 1 of Mevorach). Furthermore, Mevorach teaches that these cells can be directly administered into a joint to treat conditions such as arthritis (Paragraph 152 of Mevorach) as in instant Claim 1.
Dependent Claims taught by Saint-Remy
Saint-Remy teaches that the administration of its cells can reduce inflammation (Paragraph 70) as in instant Claim 2. Saint-Remy teaches that the subject is a human (Paragraph 44) as in instant Claim 16.
Dependent Claims taught by Mevorach
Mevorach teaches the exact cell population and apoptotic state used by applicant and the specific route of administration to use when treating osteoarthritis (Abstract and Paragraph 152 of Mevorach). Therefore, it would have been expected that the early apoptotic state cells taught by Mevorach when administered using the direct administration method to have produced the same effects of increased movement in the joint that involves increased range of movement with a reduction in pain as in instant Claim 4. Mevorach teaches administration by local injection into the joint (Paragraph 152) as in instant Claim 8. Mevorach describes an allogenic source of the cells (Abstract) as in instant Claim 9. Mevorach teaches that said apoptotic cell population comprises a pooled population of early apoptotic cells (Abstract of Mevorach) as in instant Claim 12. Mevorach teaches that the pooled early apoptotic cell population comprises an irradiated, pooled population of early apoptotic cells (Paragraph 18) as in instant Claim 13. Mevorach teaches that the apoptotic cells are prepared from single donor or from multiple donor mononuclear cells (Figure 3, Paragraph 34,Abstract ) as in instant Claim 14. Mevorach teaches that the subject is a human subject (Paragraph 200) as in instant Claim 16. Mevorach teaches wherein said administering comprises a single administration of the cells (Paragraph 236) as in instant Claim 17. Mevorach teaches multiple administrations of the apoptotic cell population (Paragraph 236) as in instant Claim 18.
Mevorach does not describe the exact administration outlined in instant claim 19. However, MPEP § 2144.05 (II) states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In reHoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc.v.Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In reKulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”); In re Williams, 36 F.2d 436, 438 (CCPA 1929) (“It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int' l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
A review of the specification fails to provide evidence that the claimed concentrations/frequency of administration is critical. Absent such evidence, it would have been obvious to an artisan of ordinary skill at the time of effectively filing to try a finite number of possible concentrations and frequency of dose to predictably arrive at the claimed concentration/dosage through routine optimization. An artisan would have a reasonable expectation of success in optimizing the concentrations because determining the dosage and frequency of such medication/therapy was long established in the art as demonstrated by Mevorach as discussed in paragraph 236. Thus, Mevorach renders the instantly claimed concentration above as in instant Claim 19. Mevorach teaches that the dosage is 30x106 to 300x106 early apoptotic cells per kg of body weight (Paragraph 151) as in instant Claim 20. Mevorach uses the exact same cell type and apoptosis state as applicant, therefore, it would be expected that administering the cells in an early apoptotic state as taught in Mevorach would reduce the concentration of at least one anti-inflammatory and/or chemokine in the joint. Mevorach specifically discusses that it’s cells are used to treat inflammation and/or inflammatory disease (Abstract) as in instant Claim 22.
Saint-Remy teaches that apoptotic cells such as mononuclear cells can be successfully used to treat disease such as autoimmune diseases, inflammatory disease, graft rejection, allergic disease, and osteoarthritis. A specific disease that the apoptotic cells can be used to treat is osteoarthritis (an inflammatory disease) as taught in paragraph 70 of Saint-Remy. Saint-Remy fails to state that its cells are in an early apoptotic state. However, Mevorach states that its mononuclear cells in the early apoptotic state can treat inflammatory diseases as well (Paragraphs 1-2 of Mevorach) and arthritis (Paragraph 30 of Mevorach). An artisan would have been motivated to use mononuclear cells in the early apoptotic state taught in Mevorach in the osteoarthritis treatment of Saint-Remy since Mevorach’s early apoptotic cells can still treat inflammatory conditions like arthritis. Furthermore, Saint-Remy does not prohibit the presence of early apoptotic cells. Given the teachings of the cited references and the level of skill of an ordinary skilled artisan at the time of applicant’s invention, it must be considered, absent evidence to the contrary, that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
All of the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention (See KSA International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007)). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.'s and Ph.D.'s. They will be medical doctors, scientists, or engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in molecular biology, immunology, and inflammatory therapy. Therefore, the level of ordinary skill in this art is high.
Response to Applicants Arguments
The independent claim has been amended to recite that the early apoptotic cells are directly administered into a joint of said subject. The newly added amendments also recite that the early apoptotic cell population comprises more than 40% Annexin V positive and less than 15% PI positive cells, wherein the cells are irradiated following induction of apoptosis. Because of the recent claim amendments, the former rejections have been withdrawn and the new rejections put forth.
Applicants argue that Saint-Remy , “did not teach that immature antigen presenting cells/mononuclear (apoptotic cells) are the cells that would treat osteoarthritis. Instead Saint-Remy teaches the immature antigen presenting cells (apoptotic cells) are used to generate T regs which are the cells responsible for treating osteoarthritis.” Even though the apoptotic cells of Saint-Remy indirectly treat osteoarthritis by generating the T reg cells, Saint-Remy’s cells are still a treatment because they generate the T reg cells which are directly responsible for treating the osteoarthritis. The instant set of claims are so broad that they do not require that the early apoptotic cells have a direct impact on the osteoarthritis. The breadth of the instant claims are so broad that they encompass administering apoptotic cells that have a direct treatment activity or an indirect treatment activity.
Furthermore, Mevorach also teaches that early apoptotic cells can be used to treat arthritis in general. An artisan would have been motivated to have used early apoptotic cells taught in Mevorach because they also can be used to treat arthritis and immune/inflammatory diseases in general (Abstract and Paragraph 30 of Mevorach).
Claims 1-2,4-6,8-9,12-20,22 are rejected under 35 U.S.C. 103 as being unpatentable over Saint-Remy (US 20150125880 in view of Mevorach (US 20180104277), Grinstaff (US 20180099072).
Saint-Remy and Mevorach apply as above to teach claims 1-2,4,8-9,12-20, and 22. Saint-Remy does not detail what synovial joints are affected by osteoarthritis and would need treatment. Grinstaff teaches that weight-bearing synovial joints such as knees, hips, feet, and spine are affected by osteoarthritis (Paragraph 4 of Grinstaff). It would have been obvious to an artisan of ordinary skill at the time of effective filing to have treated synovial joints disclosed by Grinstaff because those are weight bearing areas that are impacted by osteoarthritis (Paragraph 4 of Grinstaff). There would be a high expectation for success treating these target areas since they are known areas affected by osteoarthritis (Paragraph 4 of Grinstaff) as in instant Claims 5 and 6.
Saint-Remy teaches that apoptotic cells such as mononuclear cells can be successfully used to treat disease such as autoimmune diseases, inflammatory disease, graft rejection, and/or allergic disease. A specific disease that the apoptotic cells can be used to treat is osteoarthritis (an inflammatory disease) as taught in paragraph 70 of Saint-Remy. Saint-Remy fails to state that its cells are in an early apoptotic state. However, Mevorach states that cells in the early apoptotic state can treat inflammatory diseases as well (Paragraphs 1-2 of Mevorach) and arthritis (Paragraph 30 of Mevorach). An artisan would have been motivated to use early mononuclear cells in the early apoptotic state since they can still treat inflammatory conditions like arthritis. Furthermore, Saint-Remy does not preclude the presence of early apoptotic cells. Grinstaff teaches synovial joints that are impacted by osteoarthritis; therefore, an artisan would have been motivated to have directly treated that region. Given the teachings of the cited references and the level of skill of ordinary skilled artisan at the time of applicant’s invention, it must be considered, absent evidence to the contrary, that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
All of the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention (See KSA International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007)). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.'s and Ph.D.'s. They will be medical doctors, scientists, or engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in molecular biology, immunology, and inflammatory therapy. Therefore, the level of ordinary skill in this art is high.
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 1-2,4-6,8-9,12-14,16-17,19-20, and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1,3-5,7-10 of copending Application No. 19,174,936 in view of Mevorach (US 20180104277) (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims teach administering an early apoptotic cell population directly into a joint to treat osteoarthritis. The instant set of claims describe characteristics of the early apoptotic cells. Instant claim 1 recites that osteoarthritis can be treated by directly administering early apoptotic cells into a joint of a subject. The instant claim 1 limitation states that the “early apoptotic cell population comprises more than 40% Annexin V positive and less than 15% PI positive cells, wherein the cells are irradiated following induction of apoptosis.” Instant claim 1 also requires that the cell are irradiated. Claim 1 of Application 19/174,936 states that an early apoptotic cell population is directly administered into the knee joint of a subject to treat osteoarthritis. This claim does not specifically state that the early apoptotic cell population comprises more than 40% Annexin V and less than 15% PI positive cells; however, Mevorach teaches that the early apoptotic cells recited in Application 19/174,936 are mostly Annexin V positive but have lower level of propidium iodine (less than 15%) in paragraph 110 of Mevorach. Claim 6 of 19/174,936 further teaches that the early apoptotic cells can be irradiated. Mevorach also teaches that the early apoptotic cells are irradiated (Paragraph 18 of Mevorach)
Instant claim 2 corresponds to claim 3 of Application 19/174,936. Instant claim 4 corresponds to claim 4 of Application 19/174,936. Instant claims 5-6 correspond to claim 1 of Application 19/174,936. Instant claim 8 states that the direct administration into the joints can occur by infusion or injection of the early apoptotic cells. Mevorach states that the cells can be administered by infusion (Paragraph 205 of Mevorach) or by injection (Paragraph 33 of Mevorach). Instant Claim 9 corresponds to claim 5 of Application 19/174,936. Instant claim 12 corresponds to claim 7 of Application 19/174,936. Instant claim 13 corresponds to claim 8 of Application 19/174,936. Claim 14 corresponds to claim 9 of Application 19/174,936. Instant claim 16 states that the subject can be a human subject; Mevorach teaches that the subject can be a human subject in paragraph 200. Instant claim 17 corresponds to claim 10 of Application 19/174,936. Instant claim 18 corresponds to claim 10 of Application 19/174,936. Claim 19 corresponds paragraph 236 of Mevorach. Instant claim 20 corresponds to paragraph 151 of Mevorach. Instant claim 22 corresponds to the Abstract of Mevorach.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
All claims stand rejected.
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 LAUREN K VAN BUREN whose telephone number is (571)270-1025. The examiner can normally be reached M-F:9:30am-5:40pm; 9:00-10:00pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached at 571-272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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LAUREN K. VAN BUREN
Examiner
Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638