Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 06/23/2026 has been entered.
Status of Claims
Following Applicant’s amendment filed on 06/23/2026, claim 1 is currently amended. Claim 32 is added. Claims 1, 4-6, 13-16, 18, 20-23, 25, 27-28, and 32 are currently pending and under examination.
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.
Claim 23 is 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.
Claim 23 recites that mobilization and collection of hematopoietic stem cells “yields a low count of CD34+ cells.” The term “low count” is a relative term which renders the claim indefinite. The term “low count” is not defined by the claim, the Specification does not provide a standard for ascertaining the requisite degree of determining what quantity of CD34+ cells constitute a “low count”, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Although the Specification recognizes that the quantity of CD34+ cells affect hematopoietic stem cell engraftment, it does not specify whether “low” is determined relative to a minimum transplantable quantity, an optimal engraftment quantity, an expected collection yield, or another benchmark. Accordingly, the metes and bounds of claim 23 are rendered unclear.
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.
Claims 1, 4-6, 13-16, 18, 20-22, 25, 27-28, and 32 remain rejected under 35 U.S.C. 103 as being unpatentable over Basile et al. (Basile I, cited in previous Office Action dated 06/05/2025) in view of Awedan (cited in previous Office action dated 06/05/2025).
Regarding claims 1, 2, 4, and 13, Basile teaches administration of IL-12 for treating radiation induced injury in a subject (abstract; claim 1). They teach that IL-12 can be administered before, after, or before and after radiation therapy, which is a myeloablative therapy (claims 16-23). Administration of IL-12 restored hematopoiesis as shown by decreased leukopenia and thrombocytopenia (Fig. 12).
Although, Basile does not directly teach the reduction of infectious complications following administration of IL-12, they note that Il-12 is well known for its role in immunity by regulating inflammatory responses, innate resistance to infection, and adaptive immunity (paragraph 0159). Case law has established that a compound and all of its properties are inseparable, as are its process and yields (In re Papesch, 315 F.2d 381, 137 USPQ 43 (CCPA 1963)). In addition, case law has also established that burden is on the Applicant to show a novel and non-obvious between the claimed method and that of the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and Ex parte Gray, 10 USPQ 2d 1922 1923 (PTO Bd. Pat. App. & Int.). In the instant case, the ability of IL-12, when administered before, after, or before and after a myeloablative therapy, to reduce infectious complications would be a natural property of IL-12 when employed in this method.
Regarding claims 6, 13-16, and 18, Basile teaches that IL-12 administration post irradiation led to hematopoietic restoration via increased presence of IL-12R2-expressing progenitor cells in bone marrow including megakaryocytes, myeloid progenitors, and osteoblasts (Fig. 5; Example 20, paragraph 0325).
Regarding claim 25, Basile teaches IL-12 treatment post myeloablative treatment of subjects with cutaneous T-cell lymphoma (abstract; paragraphs 0368-0373), a hematopoietic malignancy that as evidenced by Cleveland Clinic webpage for CTCL (accessed 10/2/2024) is a low-grade non-Hodgkin lymphoma.
In regards to claim 27, Basile teaches embodiments of recombinant human IL-12 (paragraphs 0158, 0163, 0195).
However, Basile does not teach the claim 20 limitation of Il-12 administration in conjunction with myeloablative therapy and autologous transplant. Neither does it teach the limitation of claim 22 wherein mobilization and collection of hematopoietic stem cells is done prior to myeloablative therapy and the limitation of claim 23 wherein the mobilization and collection of hematopoietic stem cells yields a low count of CD34+ cells.
In regards to claim 20 and claim 21, Awedan teaches that myeloablative therapy in the form of high dose chemotherapy and/or radiation therapy is not sufficient for the treatment of hematopoietic malignancy and is associated with irreversible myelosuppression (abstract; 1st column, pg. 38). Awedan also teaches that adding hematopoietic stem cell support through either autologous or allogenic transplant following myeloablative therapy results in in lowering complications from the use of myeloablative therapy as well as increased remission rate in myeloma patients (abstract; 1st column, pg. 38).
Regarding claims 22-23, Awedan specifies that hematopoietic stem cells from peripheral blood are preferred for transplantation because they restore hematopoiesis more rapidly than do bone marrow cells and are associated with significant reduction in the duration of aplasia and transfusion requirements (1st column, pg. 39). It is well known in the art that hematopoietic stem cells isolated from peripheral blood have a lower count of CD34+ cells than those stem cells isolated from bone marrow.
Basile and Awedan are considered analogous art to the claimed invention because they are in the same field of therapeutics for hematopoietic malignancies. It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method of restoring hematopoiesis with IL-12 administration as disclosed by Basile to incorporate Awedan’s teachings of autologous or allogenic stem cell transplantation with mobilization and collection of hematopoietic stem cells low in CD34+ count from peripheral blood. Doing so would optimize hematopoiesis, increase efficiency of transfusion requirements, and improve treatment outcomes following myeloablative therapy, as recognized by Awedan. Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made.
As to claim 32, Basile I expressly teaches administering IL-12 both before and after radiation exposure including dosing intervals encompassing 24, 48, and 72 hours within the claimed range (paragraphs 0225-0228, pgs. 17-18). It would therefore have been obvious to select one IL-12 administration within 72 hours before and one within 72 hours after myeloablative therapy when applying Basile I’s expressly disclosed dosing alternatives to Awedan’s myeloablative therapy/HSCT regimen, since such selection merely employs expressly taught dose and timing parameters for the same hematopoietic recovery purpose.
Response to Arguments
Applicant's arguments filed 06/23/2026 have been fully considered but they are not persuasive.
Applicant argues that the prior art fails to teach the claimed combination of patient population, IL-12 amount, and twice dosing schedule (Applicant Remarks dated 06/23/2026, pg. 7). However, Basile I expressly teaches an IL-12 dosage range of 10 – 300 ng/kg and expressly demonstrates repeat IL-12 administration at 24 and 72 hours following total body irradiation (TBI) (paragraphs 0225-0226, pgs. 17-18). Awedan supplies the conventional myeloablative therapy/hematopoietic stem cell transplant (HSCT) setting, including autologous transplantation and stem cell mobilization. For claim 32, Basile I expressly teaches IL-12 administration both before and after irradiation within time periods encompassing the claimed 72-hour windows (paragraphs 0225-0226, 0228, pgs. 17-18). Accordingly, the claimed dose, timing, and treatment context are suggested by the combined teachings.
Applicant’s alleged unexpected results (Remarks, pg. 8) are likewise insufficient to overcome the prima facie case of obviousness. The 90% survival result relied upon by Applicant was obtained using 10 ng rMulL-12 24 hours before TBI and again three days after TBI (Specification, paragraph 0255, pg. 22), rather than the two post myeloablative doses required by claim 1. Moreover, Applicant’s reliance on the 90% survival observed with repeat dose IL-12 does not establish a statistically significant survival advantage over bone marrow transplant (BMT) or single dose IL-12. Although Example 12 reports Day 35 survival of 70% for BMT, 60% for single IL-12, and 90% for repeat dose IL-12, the Specification expressly states that “survival curves among the three active treatment groups were not significantly different from each other (Specification, paragraph 0282, pg. 25). Basile I had already demonstrated 87.5% survival following two post TBI IL-12 administration at 24 and 72 hours (paragraph 0279, pg. 23), further diminishing the asserted unexpectedness of high survival following repeat IL-12 dosing.
In addition, Applicant’s repeat dose experiment did not test the complete claimed combination of claim 32 because the repeat IL-12 animals did not also receive BMT; BMT was administered to a separate treatment group (Example 12).
Applicant’s arguments about robust platelet recovery observed in twice dosed IL-12 subjects compared to BMT treated subjects has been considered but is not found persuasive (Remarks, pg. 8). Applicant findings do not establish unexpected results commensurate with claim 1’s two post-myeloablative IL-12 administrations or claim 32’s combined IL-12 plus HSCT regimen. Objective evidence of unexpected results must be reasonably commensurate in scope with the claims for which it is offered (MPEP 716.02(d)). Accordingly, the evidence of record does not outweigh the prima facie showing of obviousness.
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.
1. Claims 1, 4-6, 13-16, 18, 20-23, 25, and 27-28, and 32 remain rejected on the on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 8921315 ('315) in view of Basile Il (J. Transl. Med., 2008, 6:26, p. 1-27, cited in the IDS filed on 03/17/2025), Chen et al (cited above), Awedan (cited above), as originally set forth on pages 13-17 of the office action mailed on 10/18/2024.
2. Claims 1, 4-6, 13-16, 18, 20-23, 25, and 27-28, and 32 remain rejected on the on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 9616106 ('106) in view of Chen et al (cited above), and Awedan (cited above), as originally set forth on pages 17-21 of the office action mailed on 10/18/2024.
3. Claims 1, 4-6, 13-16, 18, 20-23, 25, and 27-28, and 32 remain rejected on the on the ground of nonstatutory double patenting as being unpatentable over claims 1-40 of U.S. Patent No. 9636381 ('381) in view of Basile II (cited above), Chen et al (cited above), and Awedan (cited above), as originally set forth on pages 9-13 of the office action mailed on 10/18/2024.
Response to Arguments
Applicant's arguments filed 06/23/2026 have been fully considered but they are not persuasive.
While Applicant is right to point out in their response (Remarks, pgs. 8-10) that the double patenting inquiry is based upon the claims of the reference patents, the claims need not expressly recite every limitation of the presently claimed invention. An obviousness type double patenting rejection may properly rely upon the claims of the reference patent in view of a secondary reference that qualifies as prior art to establish that the differences would have been obvious (MPEP 804). Accordingly, to the extent the claims of US Patents 8921315, 9616106, and 9636381 do not expressly recite the presently claimed myeloablative therapy/HSCT setting, dosage, or timing limitations, Basile II, Chen, and/or Awedan establish that such limitations represent obvious variations for the reasons previously discussed with respect to the 103 rejection.
Furthermore, Applicant’s reliance on unexpected results is likewise unpersuasive. As discussed above, the 90% survival relied upon by Applicant was obtained using a repeat dose regiment of 10 ng rMuIL-12 administered 24 hours before and 3 days after TBI, rather than the two post myeloablative IL-12 administrations required by claim 1. Moreover, Example 12 evaluated repeat dose IL-12 and BMT in separate treatment groups and therefore did not demonstrate unexpected results for the claimed combination of repeat IL-12 administration with HSCT. Although the repeat dose group exhibited 90% survival compared with 70% for BMT and 60% for single dose IL-12, the Specification expressly states that the survival curves among the three active treatment groups were not significantly different from each other (Example 12). In addition, Example 12 administered 10 ng rMuIL-12 doses to mice weighing approximately 20 g, corresponding to approximately 500 ng/kg, which is outside the presently claimed 10-300 ng/kg range. Thus, the evidence is not reasonably commensurate in scope with amended claim 1 or new claim 32 (MPEP 716.02(d)).
Accordingly, Applicant’s arguments and evidence do not overcome the nonstatutory double patenting rejections, which are maintained.
Conclusion
No claim is allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DENNIS GEORGE whose telephone number is (571)270-0340. The examiner can normally be reached M-F 8:30am - 5pm EST.
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, Misook Yu can be reached at (571) 272-0839. 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.
/DENNIS GEORGE/Examiner, Art Unit 1644
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
Prosecution Insights