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 .
Election/Restrictions
2. Applicant’s election without traverse of Group I (claims 91-106) with species, (chemotherapeutic agent/ DNA damage inducing agent): a. anthracycline; and (C-C chemokine receptor type 5 ((CCR5) antagonist): a. small molecule in the reply filed on September 16, 2025 is acknowledged.
3. Claims 91-110 are pending.
Claims 95, 96 and 107-110, drawn to non-elected groups and non-elected species.
Claims 1-90 have been cancelled.
Claims 91-110 have been added.
Claims 91-94 and 97-106 are examined on the merits with species, species, (chemotherapeutic agent/ DNA damage inducing agent): a. anthracycline; and (CCR5 antagonist): a. small molecule.
Claim Rejections - 35 USC § 112
4. 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.
5. Claims 100-106 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, preventing and/or ameliorating doxorubicin induced mortality in mice with the administration of doxorubicin with CCR5 antagonist, maraviroc (16 mg/kg, twice daily gavage), as well as treating, preventing and/or ameliorating doxorubicin induced cardiac dysfunction in mice with the co-administration of doxorubicin with CCR5 antagonist, maraviroc (16 mg/kg, twice daily gavage), does not reasonably provide enablement for treating, preventing and/or ameliorating any and all symptoms associated with cardiotoxicity resulting from the administration of any and all chemotherapeutics, wherein the method comprises administering any and all CCR5 small molecule antagonists at or during the same time as any and all chemotherapeutic agents. 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. This data reads on some of the defined cardiac functions that are correlated with a plethora of side of effects. However, the data does not make clear if the mice cited in these figures has cancer or not and if so what is the neoplastic disease. And “Figure 21 shows a hypothetical model…”, see page 18, section 0077.
The state of the art makes clear “[c]ertain cancer treatments can damage the heart and the cardiovascular system. These side effects, including high blood pressure, abnormal heart rhythms, and heart failure…caused or exacerbated by chemotherapy and radiation therapy,”, see National Cancer Institute (NCI), Investigating the Cardiac Side Effects of Cancer Treatments (September 21, 2018) page 1, 2nd paragraph (para.).
The NCI also states “[e]ach cancer drug causes different cardiovascular issues through different mechanisms,” said Dr. [Javid] Moslehi. “To move forward, we need to know the nature of the cardiovascular toxicity.” Hence, one of ordinary skill in the art would not know whom in a vast population of patients with or without divergent and distinct cancers should be treated with this combination of therapeutic agents, as preventing a disease is a complex a process. It is not clear what parameters one skilled in the art would use in order to identify a population of subjects in which cardiotoxicity with the range of symptoms could be prevented. While it is art known that clinicians are capable of implementing both screening, surveillance and the type of screening test used and the intervals at which it is performed are based on risk stratification, which also serves as the basis for selecting potential candidates for possible prevention. However, like most screening procedures determining whether a population will eventually be struck with a disease is not fool proof.
It seems as 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 a symptom associated with cardiotoxicity resulting from the administration of any chemotherapeutic agent, thereby enhancing cardiac function, increasing/extending survival and reducing the effective dose of the chemotherapeutic agent, wherein the method comprises co-administration of any CCR5 small molecule antagonist with any chemotherapeutic 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 method as presented in the recited claims.
Given the lack of evidence, one skilled in the art would not reasonably conclude that administering any chemotherapeutic agent with any CCR5 small molecule antagonist would be effective in treating, preventing and/or ameliorating any symptom 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 broad range of CCR5 small molecule antagonists along with a broad range of chemotherapeutic agents.
Claim Rejections - 35 USC § 102
6. 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.
7. Claim(s) 91-94, 97 and 98 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, 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.
8. 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). 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. The CCR5 antagonist is to be administered in an amount of between about 150 mg and about 600 mg once or twice a day, e.g. about 150 mg once per day, or about 150 mg twice daily, or about 300 mg once per day, or about 300 mg twice daily, or about 600 mg once per day, or about 600 mg twice daily. For example, the above doses can be administered for an unlimited amount of time with doses being potentially adapted to medical needs.”, see page 14, lines 20-25.
The chemotherapy is a DNA damage inducing agent, an anthracycline, doxorubicin, epirubicin, mitoxantrone, see page 11, lines 6-27.
Claim Rejections - 35 USC § 103
9. 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.
10. Claim(s) 91-94 and 97-99 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 and/or sequentially with a chemotherapeutic agent, 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 does not teach administering the taught chemotherapeutic agent is administered contemporaneously with an effective amount of the CCR5 small molecule antagonist in the dosage range from about 1 mg/kg/day to about 100 mg/kg/day.
However, Pestell does teach “[a]ppropriate doses can be empirically determined by a person of ordinary skill in the art”, wherein the dosage seems to be dependent upon certain cancer forms expression CCR5, 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 the effective dosage(s) for 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 Pestell and teachings well known in the art that dosages of any pharmaceutical composition must be adjusted and optimized.
11. Claim(s) 91-94 and 97-99 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 teaches 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. The CCR5 antagonist is to be administered in an amount of between about 150 mg and about 600 mg once or twice a day, e.g. about 150 mg once per day, or about 150 mg twice daily, or about 300 mg once per day, or about 300 mg twice daily, or about 600 mg once per day, or about 600 mg twice daily. For example, the above doses can be administered for an unlimited amount of time with doses being potentially adapted to medical needs.”, see page 14, lines 20-25.
The chemotherapy is a DNA damage inducing agent, an anthracycline, doxorubicin, epirubicin, mitoxantrone, see page 11, lines 6-27.
Halama does not teach administering the taught chemotherapeutic agent is administered contemporaneously with an effective amount of the CCR5 small molecule antagonist in the dosage range from about 1 mg/kg/day to about 100 mg/kg/day.
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. 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 the effective dosage(s) for 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
12. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
- Pestell et al., Immune oncology therapy for breast cancer: CCR5 inhibitors enhance breast cancer cell killing and reduce doxorubicin-induced cardio-toxicity. Breast Cancer: Current Research, June 12-13, 2023 Webinar, 13th World Congress on Breast Cancer Research & Therapies, Volume 8, published June 20, 2023; and
- Weiss et al., Dexrazoxane (ICRF-187). Gen. Pharmac. Vol. 32, No. 1, pp. 155–158, 1999.
13. 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
19 November 2025
/Alana Harris Dent/Primary Examiner, Art Unit 1643