DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendments and Arguments
2. Claims 100, 102-106 and 111-116 are pending.
Claims 100, 102, 103, 105 and 106 have been amended.
Claims 91-99, 101 and 107-110 have been cancelled.
Claims 111-116 have been added.
Claims 100, 102-106 and 111-116 are examined on the merits with species, (chemotherapeutic agent/ DNA damage inducing agent): a. anthracycline; and
(CCR5 antagonist): a. small molecule.
Drawings
3. The drawings were received on July 6, 2026. This replacement sheet shows drawings Figure 11A and Figure 11B. These drawings are acceptable.
Withdrawn Grounds of Rejection
Claim Rejections - 35 USC § 102
4. The rejection of claim(s) 91-94, 97 and 98 under 35 U.S.C. 102(a)(1) as being anticipated by Pestell et al., WO 2016/209926 A1 (published 29 December 2016) is withdrawn in light of the cancellation of the claims, see Amendments to the Claims submitted July 6, 2026.
5. The rejection of claim(s) 91-94, 97 and 98 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Halama et al., WO 2016/066634 A2 (published 6 May 2016) is withdrawn in light of the cancellation of the claims, see Amendments to the Claims submitted July 6, 2026.
Claim Rejections - 35 USC § 103
6. The rejection of claim(s) 91-94 and 97-99 under 35 U.S.C. 103 as being unpatentable over Pestell et al., WO 2016/209926 A1 (published 29 December 2016) is withdrawn in light of the cancellation of the claims, see Amendments to the Claims submitted July 6, 2026.
7. The rejection of claim(s) 91-94 and 97-99 under 35 U.S.C. 103 as being unpatentable over Halama et al., WO 2016/066634 A2 (published 6 May 2016) is withdrawn in light of the cancellation of the claims, see Amendments to the Claims submitted July 6, 2026.
New and Maintained Grounds of Rejection
Claim Rejections - 35 USC § 112
8. 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.
9. The rejection of claims 100, 102-106 and new claims 111-116 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating and/or ameliorating doxorubicin induced mortality in mice with the administration of doxorubicin and CCR5 antagonists (particularly elected species, maraviroc or vicriviroc), as well as positively impacting survival with the co-administration of doxorubicin with CCR5 antagonists (particularly elected species, maraviroc or vicriviroc), does not reasonably provide enablement for treating, preventing and/or ameliorating symptoms associated with cardiotoxicity resulting from the administration of any and all DNA damage inducing agents, wherein the method comprises administering any and all CCR5 small molecule antagonists with any and all said DNA damage inducing agents. Claim 101 has been cancelled.
The declaration under 37 CFR 1.132 filed July 6, 2026 is insufficient to overcome the rejection of claims 100, 102-106 and 111-116 based upon insufficiency of disclosure under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph as set forth in the last Office action because: the declaration is not commensurate in scope. The declaration cites experiments with one DNA damaging inducing agent, doxorubicin (DOX)-induced cell death with several types of CCR5 antagonists, maraviroc (small molecule), vicriviroc (small molecule), CRISPR, anti-CCR5 humanised monoclonal antibody. While the claims have been amended to cite the chemotherapeutic agent is a DNA damage inducing agent, it is art known these agents are not one and the same as they differ in the manner of killing cancer cells, damage produced and the mechanisms by which they damage is accomplished.
Applicant asserts the test for enablement and cites figures and data within the Specification that support co-administration of DOX with a CCR5 inhibitor had increased survival, improvement in systolic dimension and cardiac function, see Remarks submitted July 6, 2026, pages 7-11. In particular, Applicant states “…DNA damage inducing agents act via a common mechanism (by damaging DNA), the skilled person would have understood that the claimed method can be practiced with an chemotherapeutic that is a DNA damaging agent, and thus were enable to practice the invention across its full scope in view of the teachings in the application without undue experimentation.”, see page 10 of the Remarks, lines 1-4.
The Remarks accompanying the declaration have been carefully considered, but fail to persuade.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
The specification provides data at section 0075 on page 17 in addition to Figures 19 and Figures 20a and 20b, which sets forth the probability of survival of the mice is increased with the co-administration of doxorubicin and maraviroc (Mar) and cardiac function is increased with the administration of said combination. Figure 20c echocardiogram data from left to right, supports the co-administration of doxorubicin and Mar has a lower left ventricular end-systolic diameter (LVESD) indicative of better function; supports the co-administration of doxorubicin and Mar has a lower left ventricular end-systolic volume (LVESV) indicative of good systolic function and the heart effectively pumps blood; supports the co-administration of doxorubicin and Mar has a high percentage indicative of a normal ejection fraction; and last panel, supports the co-administration of doxorubicin and Mar has a high percentage indicative of good heart function.
The state of the art at the time of filing, it was well known there are numerous DNA damage inducing therapies, including cytotoxic chemotherapy with five main classes that differ in mechanisms of action, see Figure 4 on page 8/22 of Reuvers et al. (DNA Damage-Inducing Anticancer Therapies: From Global to Precision Damage. Cancers 12 (2098): 1-22, published 28 July 2020). It is not clear that as the independent claims read that any DNA damage inducing agent would be able to work in concert with CCR5 antagonists thereby effectively treating, preventing or ameliorating symptoms of cardiotoxicity, increasing survival rate, extending survival time undergoing treatment with a chemotherapeutic agent associated with doxorubicin induced cardiotoxicity given “the complete mechanism of action of doxorubicin is currently still unknown and a variety of other anticancer mechanisms have been proposed.”, see page 10, section 3.2.4 in Reuvers.
It seems at this point in prosecution as Applicant’s own Specification notes, “[d]exrazoxane [a small molecule] is currently the only U.S. FDA-approved drug used clinically to prevent doxorubicin-induced (DOX-induced) cardiomyopathy. Its use has been limited to patients with metastatic breast cancer who have received a cumulative lifetime dose of at least 300 mg/m2 of DOX, or an equivalent dose of other anthracyclines. However, dexrazoxane may reduce the efficacy of anthracycline, and increase the risk of myelotoxicity, and is therefore not used routinely.”, see page 1, section 0002; and Weiss et al. (Dexrazoxane (ICRF-187) Gen. Pharmac. Vol. 32, No. 1, pp. 155–158, 1999). The NCI also cites one example, which is limited to doxorubicin and breast cancer, see One…segment spanning pages 4 and 5 of the NCI document.
Overall, these findings and the state of the art need to be interpreted with caution as few data exists on extending methods of treating symptoms associated with cardiotoxicity resulting from the administration of any DNA damage inducing agent, thereby enhancing cardiac function, increasing/extending survival, wherein the method comprises co-administration of a CCR5 small molecule antagonist with any DNA damage inducing agent.
The specification provides insufficient guidance in regard to the issues raised above and provides insufficient working examples which would provide guidance to one skilled in the art.
Granted the Office does not require that experiments under the scope of the claims produce positive and astonishing results, the experiments must be within the scope of the Forman factors (see Ex parte Forman, 230 USPQ 546, BPAI, 1986). There would also need to be some valid amount of direction or guidance, as well as presence or absence of working examples presented in the specification that would enable one skilled in the art to perform the methods as presented in the recited claims.
Given the lack of evidence, one skilled in the art would not reasonably conclude that administering any DNA damage inducing agent with a CCR5 small molecule antagonist would be effective in treating, preventing and/or ameliorating symptoms associated with cardiotoxicity. Therefore, one of skill in the art would conclude that the claimed regimen would result in an unpredictable outcome. Thus, one of skill in the art could not practice the broadly claimed method with a reasonable expectation of success.
Thus, undue experimentation would be required to implement the instantly claimed method. One skilled in the art would be forced into undue experimentation in order to practice the broadly claimed invention. Furthermore, the complexity and unpredictability of the art to which the invention retains, i.e., in vivo human therapy, suggests the need for some guidance of how to effectively use the claimed methodology to achieve human therapeutic efficacy. There would also need to be some valid amount of direction or guidance, as well as presence or absence of working examples presented in the specification that would enable one skilled in the art to perform the method as presented in the recited claims. It appears that undue experimentation would be required of one skilled in the art to practice the instant claimed invention using the teachings of the specification. See Ex parte Forman, 230 USPQ 546 BPAI, 1986.
The specification provides insufficient guidance with regard to these issues and provides no working examples, other than those mentioned herein which would provide guidance to one skilled in the art. For the above reasons, it appears that undue experimentation would be required to use the claimed invention, treating, preventing and/or ameliorating cardiotoxicity with a broad spectrum of symptoms resulting from the co-administration of a CCR5 small molecule antagonist along with a broad range of DNA damage inducing agents.
10. 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.
11. Claims 106 and 116 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.
a. Claims 106 and 116 recite the limitation "…the subject…" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 102
12. The following is a quotation of the appropriate paragraphs of 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 –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
13. Claim(s) 100, 102-104, 106, 111-114 and 116 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pestell et al., WO 2016/209926 A1 (published 29 December 2016). Pestell discloses methods of administering to a patient an effective amount of a CCR5 antagonist concomitantly, concurrently and/or sequentially with a chemotherapeutic agent and/or radiation therapy, see sections 0016-0019 and 0023 on page 5; page 13, section 0059; section 0063 spanning pages 19-21; and page 27, section 0085.
The CCR5 antagonist may be a small molecule including maraviroc and vicriviroc, wherein “[a]ppropriate doses can be empirically determined by a person of ordinary skill in the art”, see page 10, sections 0049 and 0050; page 14, section 0062, lines 1-3; page 19, 7 lines above section 0063; and page 24, section 0075. And the chemotherapeutic agent, an anthracycline includes daunorubicin, doxorubicin, epirubicin, idarubicin, mitoxantrone and doxorubicin, see page 13, section 0059.
Pestell discloses “…a first step of inhibiting the CCR5 expression in the patient, followed by a treatment of standard course of radiation or chemotherapeutic agents…”, see page 12, section 0057. With the administration of disclosed therapeutic agents, the said CCR5 small molecule and an anthracycline, the symptoms and effects on patient survival cited in independent claims 100 and 111 would be inherently realized.
14. Claim(s) 100, 102, 103, 106, 111-113 and 116 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Halama et al., WO 2016/066634 A2 (published 6 May 2016). Halama discloses administering a CCR5 antagonist to a subject receiving at least one further anti-cancer therapy including chemotherapy and radiation therapy, see page 10, lines 13-22; and page 11, lines 6-16.
The CCR5 antagonist is a small molecule, “Maraviroc (Pfizer), Vicriviroc (Schering-Plough), Aplaviroc (GlaxoSmithKline (GSK)), ancriviroc, [3H] maraviroc, [3H]ancriviroc,…TAK-779, E913, TAK-652, TAK-220, and vMIP-II” and they can be used in combination, see page 14, lines 3-19. “[D]oses can be administered for an unlimited amount of time with doses being potentially adapted to medical needs.”, see page 14, lines 24 and 25.
The chemotherapy is a DNA damage inducing agent, an anthracycline, doxorubicin, epirubicin, mitoxantrone, see page 11, lines 6-27.
With the administration of disclosed therapeutic agents, the said CCR5 small molecule and anthracycline, the symptoms and effects on patient survival cited in independent claims 100 and 111 would be inherently realized.
Claim Rejections - 35 USC § 103
15. 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.
16. Claim(s) 100, 102-106 and 111-116 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pestell et al., WO 2016/209926 A1 (published 29 December 2016). Pestell teaches methods of administering to a patient an effective amount of a CCR5 antagonist concomitantly, concurrently, simultaneously and/or sequentially with a chemotherapeutic agent and/or radiation therapy, see sections 0016-0019 and 0023 on page 5; page 13, section 0059; section 0063 spanning pages 19-21; page 24, section 0076; and page 27, section 0085.
The CCR5 antagonist may be a small molecule including maraviroc and vicriviroc, wherein “[a]ppropriate doses can be empirically determined by a person of ordinary skill in the art”, see page 10, sections 0049 and 0050; page 14, section 0062, lines 1-3; page 19, 7 lines above section 0063; and page 24, section 0075. And the chemotherapeutic agent, an anthracycline includes daunorubicin, doxorubicin, epirubicin, idarubicin, mitoxantrone and doxorubicin, see page 13, section 0059.
Pestell teaches “…a first step of inhibiting the CCR5 expression in the patient, followed by a treatment of standard course of radiation or chemotherapeutic agents…”, see page 12, section 0057. With the administration of the taught therapeutic agents, the said CCR5 small molecule and anthracycline, the symptoms and effect on patient survival cited in independent claims 100 and 111 would be inherently realized.
Pestell does not teach the method, further comprising the step of administering an additional dose of the CCR5 antagonist following administration of the chemotherapeutic agent.
However, Pestell does teach “[a]ppropriate doses can be empirically determined by a person of ordinary skill in the art”, see page 24, section 0075. It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention was made to administer the CCR5 antagonist at effective time points in the claimed treatment method including administering another dose of the CCR5 after the chemotherapeutic agent.
One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success by Pestell and teachings well known in the art that dosages of any pharmaceutical composition must be adjusted and optimized.
17. Claim(s) 100, 102-106 and 111-116 is/are rejected under 35 U.S.C. 103 as being unpatentable over Halama et al., WO 2016/066634 A2 (published 6 May 2016). Halama discloses administering a CCR5 antagonist to a subject receiving at least one further anti-cancer therapy including chemotherapy and radiation therapy, see page 10, lines 13-22; and page 11, lines 6-16.
The CCR5 antagonist is a small molecule, “Maraviroc (Pfizer), Vicriviroc (Schering-Plough), Aplaviroc (GlaxoSmithKline (GSK)), ancriviroc, [3H] maraviroc, [3H]ancriviroc,…TAK-779, E913, TAK-652, TAK-220, and vMIP-II” and they can be used in combination, see page 14, lines 3-19. “[D]oses can be administered for an unlimited amount of time with doses being potentially adapted to medical needs.”, see page 14, lines 24 and 25.
The chemotherapy is a DNA damage inducing agent, an anthracycline, doxorubicin, epirubicin, mitoxantrone, see page 11, lines 6-27.
With the administration of disclosed therapeutic agents, the said CCR5 small molecule and anthracycline, the symptoms and effects on patient survival cited in independent claims 100 and 111 would be inherently realized.
Halama does not teach the method, wherein the CCR5 antagonist is administered prior to the chemotherapeutic agent and further comprising the step of administering an additional dose of the CCR5 antagonist following administration of the chemotherapeutic agent.
However, Halama does teach “"therapeutically effective amount" or "therapeutic amount" are intended to mean that amount of a drug or pharmaceutical agent that will elicit the biological or medical response of a tissue, a system, animal or human that is being sought by a researcher, veterinarian, medical doctor or other clinician. The dosage regimen utilizing a CCR5 antagonist as described herein can be selected by the skilled practitioner in accordance with a variety of factors including type, species, age, weight, body mass index, sex and medical condition of the patient; the severity of the condition to be treated; the potency of the compound chosen to be administered; the route of administration; the purpose of the administration;…., see para. bridging pages 7 and 8. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention was made to administer the CCR5 antagonist at effective time points, whether before the administration of the chemotherapeutic agent and/or an addition dose of CCR5 antagonist after administration of the chemotherapeutic agent within the claimed treatment method.
One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success by Halama and teachings well known in the art that dosages of any pharmaceutical composition must be adjusted and optimized.
Conclusion
18. 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(20a).
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.
19. Any inquiry concerning this communication or earlier communications from the Examiner should be directed to ALANA HARRIS DENT whose telephone number is (571)272-0831. The Examiner works a flexible schedule, however she can generally be reached on 8AM-8PM, Monday through Friday.
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, Julie Wu can be reached on 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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ALANA HARRIS DENT
Primary Examiner
Art Unit 1643
10 September 2026
/Alana Harris Dent/Primary Examiner, Art Unit 1643
