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 .
Priority
This application is a continuation of Application No. 18/618720 (filed on 3/27/2024), which is a continuation of Application No. 17/743097 (filed on 5/12/2022), which is a continuation of Application No. 16/101676 (filed on 8/13/2018), which in turn is a continuation of Application No. 15/834017 (filed on 12/06/2017).
Specification
The abstract of the disclosure is objected to because the Latin term “ex vivo” is not italicized. Correction is required. See MPEP § 608.01(b).
Claim Objections
Claim 1 is objected to because of the following informalities: abbreviations are used without providing their full form. Any abbreviation should be provided defined when first recited in a set of claims by spelling out the full term followed by the abbreviation within parenthesis. Thus, “CXCR2”, “Gro-β”, “Gro-β T”, and “CXCR4” should be amended to “C-X-C chemokine receptor type 2 (CXCR2)”, “growth-regulated protein beta (Gro-β)”, “truncated Gro-β (Gro-β T)”, and “C-X-C chemokine receptor type 4 (CXCR4)”, respectively.
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.
Claim 1 is rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor at the time the application was filed, had possession of the claimed invention.
Claim 1 recites “Gro-β, Gro-β T, and variants thereof” The term “variants” is defined in the specification as the following: As used herein, the terms “variant” and derivatives” are used interchangeably and refer to naturally-occurring, synthetic, and semi-synthetic analogues of a compound, peptide, protein, or other substance described herein. A variant or derivative of a compound, peptide, protein, or other substance described herein may retain or improve upon the biological activity of the original material (lines 8-12, page 88).
To satisfy the written description aspect of 35 U.S.C. 112(a) for a claimed genus, it must be clear that: (1) the identifying characteristics of the claimed molecules have been disclosed, e.g., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics; and (2) a representative number of species within the genus must be disclosed. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Applicant discloses that suitable CXCR2 agonists include Gro-β and “variants” thereof such as the truncated form Gro-β T (having deletion of the first four amino acids from the N-terminus), as well as mutants Gro-β N69D (having a mutation of asparagine residue at position 69 of SEQ ID NO:1) and Gro-β N65D (having a mutation of asparagine residue at position 65 of SEQ ID NO:2) (Table 7, page 177). In addition, “variants” include: other truncated forms of Gro-β T (lines 13-17, page 176); peptides that have one or more amino acid substitutions, insertions, and/or deletions relative to Gro-β, Gro-β T (lines 4-6 and 16-18, page 177), Gro-β N69D, or Gro-β N65D (lines 1-3 and 12-14, page 178); and peptides having at least 85% sequence identity to the amino acid sequence of SEQ ID NO:1, SEQ ID NO: 2 (lines 8-11 and 19-22, page 177), SEQ ID NO:3, or SEQ ID NO: 4 (lines 4-6 and 15-18, page 178).
Thus regarding the first requirement of having disclosure identifying characteristics of the claimed variants, Applicant has identified a core structure (Gro-β or SEQ ID NO:1) and function (activates CXCR2) that must be shared by all variants.
But regarding disclosure of a representative number of species within the genus,
review of the specification shows that this second requirement is not met by Applicant. The number of chemokines that can be considered variants of Gro-β is large. However, the instant application only sufficiently describes Gro-β T and demonstrates its effectiveness in mobilizing hematopoietic stem cells into the peripheral blood (Example 1, pages 207-213). Note that disclosure of a single species does not constitute a representative number for such a broad genus as is encompassed by the breadth of “variants”. A representative number of species, as would be required to support description and to show possession of the entire genus, is lacking.
Hence, it cannot be determined whether Applicant was in possession of the invention before the effective filing date of the claimed invention.
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.
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.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Bridger et al. (Pub. No. US 2006/0035829 A1) in view of Pelus et al. (Experimental Hematology 2006, Vol. 34, pages 1010-1020).
Bridger et al. teaches methods of progenitor/stem cell mobilization using combination therapy (par. [0002]) based on the finding that the combination of a CXCR4 antagonist and GRO[Symbol font/0x62] is effective in mobilizing cells (par. [0011]). In an embodiment, the mobilized cells are bone marrow cells (par. [0014]). According to Bridger et al., CD34+ cells are present in large numbers in the bone marrow and CD34 is considered a marker for stem cells (par. [0038]), i.e., bone marrow cells comprise CD34+/stem cells.
The combination of a CXCR4 antagonist and a GRO[Symbol font/0x62] protein can be administered directly to a subject, or used to treat cells ex vivo and then administered to a subject (par. [0032]). Subjects include animals, particularly veterinary and human subjects, that are treated to increase the number of progenitor and/or stem cells. Accordingly, Bridger et al.’s methods are useful for stem cell transplantation, tissue repair, and situations needing direct in vivo stimulation (par. [0013]).
The components of the disclosed combination can be administered as a mixture or independently, at the same or different times, by the same or different routes (par. [0032]). The components are preferably administered by injection, most preferably through intravenous injection but also includes subcutaneous injection (par. [0597]).
The CXCR4 antagonist is preferably a compound having formula (1) as described (par. [0030]). One of the particularly preferred embodiments of formula (1) is 1,1’-[1,4-phenylene-bis(methylene)]-bis-1,4,8,11-tetraazacyclotetradecane, which is called AMD3100 (par. [0591]).
The GRO[Symbol font/0x62] combined with the CXCR4 antagonist includes not only GRO[Symbol font/0x62] itself but also modified forms such as truncated, multimerized, and mutated (containing amino acid substitutions, deletions, or insertions) forms of GRO[Symbol font/0x62] (par. [0033], [0594]).
When CXCR4 inhibitor is administered alone, suitable dosage is about 0.1 µg/kg to 5 mg/kg of body weight. But when administered in combination with GRO[Symbol font/0x62], the dosage for the CXCR4 antagonist is 2x lower (0.05 to 2,500 µg/kg of body weight) or 4x lower (0.025-1,250 µg/kg of body weight) (par. [0600]).
In Example 4, the CXCR4 antagonist AMD3100 is injected subcutaneously at a dose of 5 mg/kg while GRO[Symbol font/0x62] is separately or simultaneously injected subcutaneously at a dose of 2.5 mg/kg. Experimental data show that the combination of GRO[Symbol font/0x62] and AMD3100 caused greater peripheral blood mobilization of progenitor cells, neutrophils, and total white blood cells compared to either component alone (par. [0627]).
Bridger et al.’s methods of progenitor/stem cell mobilization are comparable to the instant application’s method as explained below:
Regarding claim 1: administering a GRO[Symbol font/0x62] protein (which includes GRO[Symbol font/0x62] and its modified forms like truncated GRO[Symbol font/0x62]) and a CXCR4 antagonist like AMD3100 to a subject is analogous to the step “administering to the donor (i) a CXCR2 agonist selected from the group consisting of Gro-[Symbol font/0x62], Gro-[Symbol font/0x62] T, and variants thereof… and (ii) a CXCR4 antagonist”.
The method resulting in the mobilization of progenitor and/or stem cells like bone marrow cells (par. [0014]), which comprise CD34+/stem cells, to the peripheral blood of the administered subject, wherein the subject includes human subjects (par. [0013]) which are mammals, meets the claimed method’s intended function of “mobilizing a population of hematopoietic stem cells from the bone marrow of a mammalian donor into peripheral blood”.
Bridger et al. is different from the claimed invention in that the GRO[Symbol font/0x62] protein is not taught to be administered at a dose of “from about 50 µg/kg to about 300 µg/kg”.
Despite this, Pelus et al. demonstrates that a single subcutaneous injection of GRO[Symbol font/0x62] at a dose of 250 µg/kg in mice and rhesus monkeys is effective in mobilizing hematopoietic progenitor cells (Table 1, page 1012). Mobilization is significantly enhanced when GRO[Symbol font/0x62] is administered 16 hours after the last dose of granulocyte colony-stimulating factor (G-CSF) (Table 2, page 1012). Since the GRO[Symbol font/0x62] dose taught by Pelus et al. promotes mobilization, a person with ordinary skill in the art before the effective filing date of the claimed invention would have modified the methods of Bridger et al. by administering a single GRO[Symbol font/0x62] dose of 250 µg/kg. It can be predicted that such modification would lead to successful mobilization of hematopoietic progenitor cells to the peripheral blood. The obviousness of the instant claim is based on some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. See MPEP § 2143.01 and KSR International Co. v. Teleflex Inc., 550 U.S. 398, 82 USPQ2d 1385, 1395-97 (2007).
Hence, claim 1 is obvious over Bridger et al. in view of Pelus et al..
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.
Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 10,058,573.
The U.S. patent is directed to a method of mobilizing a population of hematopoietic stem cells from the bone marrow of a human donor into peripheral blood. The method comprises administering to the donor (i) Gro-β T at a dose of about 150 μg/kg, wherein the Gro-β T is administered intravenously to the donor and (ii) 240 μg/kg plerixafor or a pharmaceutically acceptable salt thereof, wherein the plerixafor or pharmaceutically acceptable salt thereof is administered subcutaneously to the donor.
In one embodiment, the method produces a population of cells having a ratio of CD34+ cells to leukocytes of from 0.0008 to 0.0021 in a sample of peripheral blood of the donor following administration; or enriches the donor’s peripheral blood with CD34+ cells relative to leukocytes by a ratio of from 3.4:1 to 6.9:1 as assessed by comparing a sample of peripheral blood of the donor following administration to one prior to administration.
In another embodiment, the method produces a population of cells having a ratio of CD34+ cells to neutrophils of from 0.0018 to 0.0058 in a sample of peripheral blood of the donor following administration; or enriches the donor’s peripheral blood with CD34+ cells relative to neutrophils by a ratio of from 2.1:1 to 8.1:1 as assessed by comparing a sample of peripheral blood of the donor following administration.
The disclosed method also teaches that the Gro-β T is administered intravenously to the donor, while the plerixafor or a pharmaceutically acceptable salt thereof is administered subcutaneously to the donor.
The U.S. patent therefore anticipates the claims of the instant application.
Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 8-9 of U.S. Patent No. 11,260,079.
U.S. patent 11,260,079 is drawn to a method of performing an allogeneic hematopoietic stem cell transplant in a patient in need thereof by infusing into the patient a therapeutically effective amount of allogeneic hematopoietic stem cells.
The claims at issue are not identical, but they are not patentably distinct from each other because the hematopoietic stem cells are specified to be mobilized from bone marrow of a human donor into the donor’s peripheral blood by a method comprising administering to the donor (i) Gro-β T at a dose of from about 50 μg/kg to about 150 μg/kg and (ii) plerixafor (which is a CXCR4 antagonist) or a pharmaceutically acceptable salt thereof at a dose of about 240 μg/kg, wherein the Gro-β T is administered intravenously and wherein the plerixafor or pharmaceutically acceptable salt thereof is administered subcutaneously.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHELLE F PAGUIO FRISING whose telephone number is (571)272-6224. The examiner can normally be reached Monday-Friday, 8:00 a.m. - 4:00 p.m..
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melenie L. Gordon can be reached at (571) 272-8037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Michelle F. Paguio Frising/Primary Examiner, Art Unit 1651
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