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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 10/30/2025 has been entered.
Status of the Claims
Claims 1 – 7, 14 – 15, 37 – 40, 43, and 49 – 53 were pending. Claims 1, 5, 37 – 39 have been amended. Claims 1, 5, 37 – 39, and 49 – 53 are currently pending, with non-elected claims 49 – 50 and 52 – 53 withdrawn from consideration. Claims 1, 5, 37 – 39, and 51 are the subject of this Office Action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/30/2025 is in compliance with the provisions of 37 CFR 1.97 and has been considered.
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.
Previous rejection, withdrawn: claims 1, 2, 5, 37 – 43, and 51 were rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AlA), first paragraph, as failing to comply with the written description requirement.
In view of the claim amendments of 02/18/2026, this rejection is withdrawn.
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.
New rejection, necessitated by amendment: claims 1, 5, 37 – 39, and 51 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.
The term “increased nfP2X7 expression” in claim 1 is a relative term which renders the claims indefinite. The term “increased nfP2X7 expression” is not defined by the claims, and the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is not clear as to what degree the nfP2x7 is increased or what concentration increasing an amount of nfP2x7 leads to.
Claims 5, 37 – 39, and 51 depend from present claim 1 and thus inherit the deficiencies of claim 1.
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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
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.
Previous rejection, withdrawn: claims 40 and 43 were rejected under 35 U.S.C. 103 as being unpatentable over US2012/0282278 A1, Barden et al [“BARDEN”], published November 8, 2012 (see PTO-892: Notice of References Cited of 03/12/2025), in view of “The Interplay of Immunotherapy and Chemotherapy: Harnessing Potential Synergies,” Emens et al, published May 2015 (see PT)-892 of 07/31/2025).
In view of the cancelation of claims 40 and 43 in the claim amendments of 02/18/2026, this rejection is withdrawn.
Previous rejection, withdrawn: claims 1, 2, 5, 37, 38, and 51 were rejected under 35 U.S.C. 103 as being obvious over US2012/0282278 A1, Barden et al, published November 8, 2012 (see PTO-892 of 03/12/2025) in view of “The P2X7 receptor is a key modulator of the PI3K/GSK3B/VEGF signaling network: evidence in experimental neuroblastoma,” Amoroso et al, published January 26, 2015 (see PTO-892 of 03/12/2025), and “Drug resistance in human neuroblastoma cell lines correlates with clinical therapy”, Keshelava et al, published October 1997 (see PTO-892 of 03/12/2025).
In view of the claim amendments of 02/18/2026, this rejection is withdrawn.
New rejection, necessitated by claim amendments: claims 1, 5, 37 – 39, and 51 are rejected under 35 U.S.C. 103 as being unpatentable over BARDEN 2 (Barden JA, et al. (2016) Therapeutic targeting of the cancer-specific cell surface biomarker nfP2X7. J Clin Cell Immunol 7:432; an IDS reference submitted 10/30/2025) in view of BARDEN.
The present application is directed to a method of treatment, comprising (a) determining the expression of nfP2X7 (non-functional P2X7) receptor in a sample from an individual, wherein the individual has cancer and the sample comprises tumor cells that are resistant to chemotherapy or radiotherapy;(b) identifying the tumor cells as having increased nfP2X7 expression; and administering a P2X7 receptor targeted therapy to the individual; wherein the therapy comprises an anti-nfP2X7 receptor antibody or fragment thereof, wherein the anti-nfP2X7 receptor antibody or fragment thereof is or comprises a variable domain selected from the group consisting of: a single domain antibody (sdAb), a single chain Fv fragment (scFv), F(ab')2, Fab, Fd and Fv fragments; and wherein the variable domain binds to cancer-associated P2X7 receptors that have an impaired response to ATP such that they are unable to form an apoptotic pore under normal physiological conditions and wherein the variable domains do not bind P2X7 receptors that do not have an impaired response to ATP.
BARDEN 2 is directed to nfP2X7, which is a receptor that, unlike P2X7, cannot enable apoptosis in cancer cells and because of the established the widespread coverage of human cancers in which the aberrant receptor is found, attention has been drawn to the therapeutic potential of the target and whether an immunotherapeutic approach is capable of providing a significant therapeutic response. BARDEN 2 demonstrates an anti-nfP2X7 intrinsic target specificity, the delivery of antibody within target cells, the extremely good safety profile of the targeting antibody and the broad range of cancer tissue that could be treated in both humans and other animals. See abstract.
BARDEN 2 teaches an increase in nfP2X7 receptor expression with tumor grade. See p. 2, right column, last paragraph – p. 3, right column, first paragraph and Figure 2.
Furthermore, BARDEN 2 teaches that human D270 malignant glioma cells, resistant to low levels of cisplatin (a chemotherapeutic agent), were tested to determine whether there was augmented cell killing in the presence of the sheep anti-P2X7 IgG antibody. BARDEN 2 discloses that at 24 nM the anti-nfP2X7 antibody increased cell killing to 47% compared with 23% with the control, a concentration that is readily attainable in serum by intravenous injection See p. 3, right column, last paragraph – p. 4, left column, first paragraph and Figure 6, p. 6.
BARDEN 2 teaches that the P2X7 receptors expressed on the surface of the cancer cells (identified as non-functional for pore formation and called nfP2X7 ) are unable to induce apoptosis and lack the ability to form dilated pores. See p. 1, left column, last paragraph.
BARDEN is directed to an antigen binding site for binding to a P2X7 receptor. See abstract. BARDEN teaches a method for the treatment of cancer or a condition or disease associated with expression of non-functional P2X7 receptor in an individual including the step of providing an antigen binding site to an individual requiring treatment for cancer or said condition or disease. See claim 43.
Regarding claims 1 and 5, BARDEN 2 and BARDEN renders the method of treatment obvious. BARDEN teaches a method for the treatment of cancer or a condition or disease associated with expression of non-functional P2X7 receptor in an individual including the step of providing an antigen binding site, immunoglobulin variable domain, antibody, Fab, dab, scFv, diabody, triabody, fusion protein, conjugate or pharmaceutical composition as described herein to an individual requiring treatment for cancer or said condition or disease (see paragraph 0039), and BARDEN 2 teaches that nfP2X7 is a P2X7 receptor with an increased expression in tumor cells and an inability to form an apoptotic pore. Furthermore, BARDEN 2 teaches that an anti-nfP2X7 antibody increases the killing of human D270 malignant glioma cells that were resistant to a chemotherapeutic agent.
Thus, it would have been obvious to one having ordinary skill in the art to arrive to the method of treatment recited in present claims 1 and 5 via the teachings of BARDEN and BARDEN 2. There would have been a reasonable expectation of success considering that endogenous nfP2X7 is known to contribute to the survival of tumor cells and an anti-nfP2X7 antibody is known in the treatment of cancer as evidenced by the applied prior art.
Regarding claims 37 - 39, BARDEN 2 teaches the chemotherapy agent cisplatin (a platinum-based agent). See p. 3, right column, last paragraph – p. 4, left column, first paragraph and Figure 6, p. 6.
Regarding claim 51, BARDEN teaches neuroblastoma as an example of one of the cancers that can be treated with the disclosed P2X7 receptor antibody [0245].
Response to Arguments
On pgs. 10 – 11 of the reply of 10/30/2026, Applicant argues that “[t]he cited art does not identify nfP2X7 as a target for treatment of chemotherapy-resistant cancers”; on pgs. 11 – 13, Applicant also argues that that “[t]he solution to the problem of chemoresistant cancer is not known in the art”; and on pgs.12 – 13, Applicant argues that “[t]he claimed invention could not be obviously derived from the prior art”.
Applicant’s arguments are not persuasive because, as discussed above, BARDEN 2 teaches the increased cell killing of chemotherapy-resistant human D270 malignant glioma cells with the addition of an anti-nfP2X7 antibody. According to the present claims, cisplatin is a chemotherapeutic agent (present claims 38 – 39). BARDEN 2 teaches the treatment of cisplatin-resistant human D270 malignant glioma cells. See p. 3, right column, last paragraph – p. 4, left column, first paragraph and Figure 6, p. 6. Because human D270 malignant glioma cells represents a model of human glioblastoma, there would have been obvious to treat an individual having tumor cells that are resistant to chemotherapy with an anti-nfP2X7 receptor antibody.
Furthermore, because BARDEN and BARDEN 2 focuses on nfP2X7 as a target in the treatment of tumor cells and show the effectiveness of an anti-nfP2X7 antibody in the killing of tumor cells, a regimen such as that recited in present claim 1 would have a reasonable expectation of success.
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.
Previous rejection, withdrawn: claims 1, 2, 5, 40-43, and 51 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 16, and 17 of U.S. Patent No. 12097265 in view of “The P2X7 receptor is a key modulator of the PI3K/GSK3B/VEGF signaling network: evidence in experimental neuroblastoma”, Amoroso et al, published January 26, 2015.
In view of the claim amendments in the reply of 02/18/2026, this rejection is withdrawn.
New rejection, necessitated by claim amendments: claims 1, 5, 37 – 39, and 51 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 19 of U.S. Patent No. 12,097,265 in view of BARDEN 2 and BARDEN.
Patented claim 1 recites a cytotoxic particle including: a liposome; a prodrug of a cytotoxic compound contained in, or entrapped in or on a lipid bilayer of said liposome; a plurality of variable domains arranged on the liposome for binding to P2X7 Receptors (P2X7R) on a cancer cell thereby enabling the particle to bind to a cancer cell having P2X7R expressed thereon when the particle is contacted with the cancer cell, wherein the variable domains are selected from the group consisting of: a single domain antibody (sdAb), a single chain Fv fragment (scFv), F(ab′)2, Fab, Fd and Fv fragments;
wherein the variable domains bind to cancer-associated P2X-R that have an impaired response to ATP such that they are unable to form an apoptotic pore under normal physiological conditions and wherein the variable domains do not bind P2X-R that do not have an impaired response to ATP.
Patented claim 16 recites a method of treating an individual having cancer including administering a particle of claim 1 to the individual, thereby treating the individual for cancer.
17. The method of claim 16, wherein the cancer is a solid tumour.
The main difference between the present claims and the patented claims is that the present claims recite that the method comprises (a) determining the expression of nfP2X7 (non-functional P2X7) receptor in a sample from an individual, wherein the individual has cancer and the sample comprises tumor cells that are resistant to chemotherapy or radiotherapy; (b) identifying the tumor cells as having increased nfP2X7 expression. However, BARDEN and BARDEN 2 render these limitations obvious. The teachings of BARDEN and BARDEN 2, and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 103 above.
Because the patented claims recite a composition with a single domain antibody (sdAb), a single chain Fv fragment (scFv), F(ab′)2, Fab, Fd and Fv fragments that bind to cancer-associated P2X-R that have an impaired response to ATP such that they are unable to form an apoptotic pore under normal physiological conditions and wherein the variable domains do not bind P2X-R that do not have an impaired response to ATP, that is administered in a method of treating an individual having cancer, and BARDEN 2 teaches that tumor cells have an increased nfP2X7 expression and teaches that targeting the nonfunctional P2X7 in cancer cells that are resistant to chemotherapy render the method of present claim 1 obvious to one having ordinary skill in the art.
New rejection, necessitated by claim amendments: claims 1, 5, 37 – 39, and 51 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 19 of U.S. Patent No. 11,260,131 in view of BARDEN 2 and BARDEN.
Patented claim 1 recites a cytotoxic particle including: a liposome; a prodrug of a cytotoxic compound contained in or on a lipid bilayer of said liposome; a plurality of variable domains arranged on the liposome for binding to P2X7 receptors on a cancer cell thereby enabling the particle to bind to a cancer cell having P2X7 receptors expressed thereon when the particle is contacted with the cancer cell,
wherein the variable domains are selected from the group consisting of: a single domain antibody (sAb), a single chain Fv fragment, F(ab′)2, Fab, Fab′, Fd and Fv fragments, wherein the variable domains bind to cancer associated P2X7 receptors that have an impaired response to ATP such that they are unable to form an apoptotic pore under normal physiological conditions and wherein the variable domains do not bind P2X7 receptors that do not have an impaired response to ATP; and wherein the variable domains comprise: a CDR1 having the amino acid sequence of RNHDMG (SEQ ID NO: 4); a CDR2 having the amino acid sequence of AISGSGGSTYYANSVKG (SEQ ID NO: 5); and a CDR3 having the amino acid sequence of EPKPMDTEFDY (SEQ ID NO: 6).
Patented claim 11 recites a method of treating an individual having cancer including administering a particle of claim 1 to the individual, thereby treating the individual for cancer.
The main difference between the present claims and the patented claims is that the present claims recite that the method comprises (a) determining the expression of nfP2X7 (non-functional P2X7) receptor in a sample from an individual, wherein the individual has cancer and the sample comprises tumor cells that are resistant to chemotherapy or radiotherapy; (b) identifying the tumor cells as having increased nfP2X7 expression. However, BARDEN and BARDEN 2 render these limitations obvious. The teachings of BARDEN and BARDEN 2, and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 103 above.
Because the patented claims recite a composition with a single domain antibody (sAb), a single chain Fv fragment, F(ab′)2, Fab, Fab′, Fd and Fv fragments, wherein the variable domains bind to cancer associated P2X7 receptors that have an impaired response to ATP such that they are unable to form an apoptotic pore under normal physiological conditions and wherein the variable domains do not bind P2X7 receptors that do not have an impaired response to ATP that is administered in a method of treating an individual having cancer, and BARDEN 2 teaches that tumor cells have an increased nfP2X7 expression and teaches targeting the nonfunctional P2X7 in cancer cells that are resistant to chemotherapy render the method of present claim 1 obvious to one having ordinary skill in the art.
Conclusion
Claims 1, 5, 37 – 39, and 51 are rejected.
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/ESTELLA M. GUSTILO/Examiner, Art Unit 1646
/PETER J REDDIG/Primary Examiner, Art Unit 1646