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 .
DETAILED ACTION
Claims 1-20 are pending in the instant application.
Claims 1-20 are examined herein.
Priority
The instant application is a DIV of U.S. Patent Application No. 16/756,720, filed on 16 April 2020, and claims benefit of foreign priority to LU100487, filed on 17 October 2017 and the benefit of priority to PCT/EP2018/078335, filed on 17 October 2018. The claims to the benefit of priority are acknowledged. It is noted, however, that applicant has not filed a certified copy of the priority application as required by 37 CFR 1.55. As such, the effective filing date of the claims is 17 October 2018.
Information Disclosure Statement
No information disclosure statement (IDS) submitted by applicant.
Claim Interpretation
While the specification does not provide a representative number of species of bacteria demonstrating the method of treating a RNA viral infection with a bacterial co-infection where the bacteria is selected from Staphylococcaceae, Streptococcaceae, Legionellaceae, Pseudomonadaceae, Bacillaceae, Chlamydiaceae,Mycoplasmataceae, Enterobacteriaceae, Pseudomonadales and/or Pasteurellaceae. The listed families are known in the art to activate the MEK pathway in infected subjects thereby inducing inflammatory responses.
While the specification does not provide any working examples of PD-0184264 co-administered with a neuraminidase inhibitor this combination would be considered obvious as neuraminidase inhibitors are known to treat influenza A and B; therefore sharing utility.
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.
Claims 1-14 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 influenza viral infection and its co-infection with bacterial infection, does not reasonably provide enablement for preventing any viral infection or treating other viral infections and their co-infection with a bacterial infection. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The instant claims are drawn to a method of treating or preventing RNA virus infections and/or co-infection with a bacterial infection comprising administering a therapeutically effective amount of PD-0184264. The specification fails to provide information that would allow the one skilled in the art to practice [insert].
To be enabling, the specification of the patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation. In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993). Explaining what is meant by "undue experimentation," the Federal Circuit has stated:
The test is not merely quantitative, since a considerable amount of experimentation is
permissible, if it is merely routine, or if the specification in question provides a reasonable
amount of guidance with respect to the direction in which the experimentation should
proceed to enable the determination of how to practice a desired embodiment of the
claimed invention. PPG v. Guardian, 75 F.3d 1558, 1564 (Fed. Cir. 1996).
The factors that may be considered in determining whether a disclosure would require undue experimentation are set forth by In re Wands, 8 USPQ2d 1400 (CAFC1988) at 1404 where the court set forth the eight factors to consider when assessing if a disclosure would have required undue experimentation. Citing Ex parte Forman, 230 USPQ 546 (BdApls 1986) at 547 the court recited eight factors:
the nature of the invention
the state of the prior art
the predictability of the art
the amount of direction or guidance provided
the presence or absence of working examples
the breadth of the claims
the quantity of experimentation necessary
the relative skill of those in the art
These factors are always applied against the background understanding that scope of enablement varies inversely with the degree of unpredictability involved. In re Fisher, 57 CCPA 1099, 1108, 427 F.2d 833, 839, 166 USPQ 18, 24 (1970). Keeping that in mind, the Wands factors are relevant to the instant fact situation for the following reasons:
The nature of the invention - is a method of treating or preventing RNA virus infections and/or co-infection with a bacterial infection comprising administering a therapeutically effective amount of PD-0184264.
The state of the prior art - the pharmacological art requires the screening of potential drug candidates in vitro and in vivo to determine if the drug candidates exhibit the desired pharmacological activities.
In order to treat a disease: one would need to precisely identify what the disease is, identify what biological target is connected with the disease, demonstrate that the drug candidate in some way modulates the normal processes of the biological target, and demonstrate that a patient benefited from such modification without detrimental side effects. Typically, this process includes in vitro laboratory screening, preclinical in vivo screening, and three phases of clinical trials. Once this arduous process has been successfully completed by a drug candidate, subsequent drug candidates will benefit from the established proof of concept. The subsequent drug candidates must demonstrate a substantial correlation between their biological activity and that of the known drug candidate.
In order to prevent a disease: one would need to precisely identify those subjects likely to acquire such a disease, administer Applicant’s claimed invention, and demonstrate that the patient did not develop the disease as a result of the administration of the claim invention.
In the instant case, the prior arts recognize that MEK inhibitors have the potential to treat some RNA virus infections. However there is no known small molecule inhibitor to treat or prevent all RNA virus infections. Pleschka et al. (WO2014056894A1) demonstrate MEK inhibitors can treat influenza, a negative strand RNA virus. While Baturcam et al. (Cell Commun Signal. 2019;17:78) demonstrates that a MEK inhibitor was able to reduce viral load in rhinovirus, a positive-strand RNA virus. However, Baturcam also demonstrates the inability for the same MEK inhibitor to reduce viral load in respiratory syncytial virus, a negative strand RNA virus. All three RNA viruses use the Raf/MEK/ERK signaling pathway to promote replication, yet not all respond to MEK inhibition.
The predictability or unpredictability of the art – the law recognizes the pharmaceutical art as an unpredictable art and requires each embodiment to be individually assessed for physiological activity. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18 24 (CCPA 1970). Accordingly, the more unpredictable an area is the more specific disclosure is necessary in order to satisfy the statute. Section 2164.02 of the MPEP provides:
"[C]orrelation” as used herein refers to the relationship between in vitro and in
vivo animal model assays and a disclosed or a claimed method of use . . . if the
art is such that a particular model is recognized as correlating to a specific
condition, then it should be accepted as correlating unless the examiner has
evidence that the model does not correlate.
In light of these remarks, the Examiner finds that one of ordinary skill in the art would agree with the court; that is, the pharmaceutical art is unpredictable. Thus, a substantial correlation is necessary for establishing the potential of new therapeutics.
The amount of direction or guidance presented – the instant specification briefly discusses the implication of MEK inhibitors in the treatment of influenza virus (page 1). There is no direction or guidance provided that supports a use of a MEK inhibitor as a drug for treating or preventing all RNA virus infections and/or co-infection with bacterial infection.
The amount of guidance or direction to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. MPEP § 2164.03 (quoting In re Fisher, 427 F.2d 833, 839, 166 USPQ 18 24 (CCPA 1970)). As identified supra, the pharmaceutical art is recognized as unpredictable.
Thus, in order to support a claim for treating or preventing all RNA virus infections a vast amount of evidence is required because such a claim is not supported by the prior art or the instant specification.
The presence or absence of working examples - there are no working or prophetic examples in the specification that demonstrate that the instant compound may prophylactically treat and prevent all RNA virus infections. The assays in the specification demonstrate that the instant compound was tested for its ability to treat influenza A (pages 21-24). There is no guidance, direction, or demonstration in the specification that the antiviral activity of PD-0184264 against influenza virus would be extrapolated to all RNA virus diseases.
The breadth of the claims – is incommensurate in scope with the disclosure because a fair reading of the specification fails to support a finding that PD-0184264 may treat or prevent all RNA viral diseases in a patient.
The quantity of experimentation necessary – generally speaking, the amount of experimentation to transform a molecule into medicine is vast and the success thereof is low. Recent statistics indicate that the attrition rates during drug development remain high. Schafer et al. Drug Discovery Today 2008, 13 (21/22), 913-916. The article makes clear that there are many steps necessary to promote a new molecular entity toward its clinical use, any one of which is cumbersome.
For instance, Schafer et al. discloses: "proof of concept trials have failed when the decision to enter clinical development was based on preclinical experiments using the wrong compound, the wrong experimental model, or the wrong endpoint.” It can be gleaned from this article that a plethora of experimentation is needed to identify the lead compound (i.e. one among many in a Markush-type claim), to establish which preclinical tests are predictive of clinical success, and to establish which diseases are the best to target for each lead compound.
There is generally a vast amount of experimentation to take a drug from bench to the clinic. See e.g., Horig et al. Journal of Translational Medicine 2004, 2(44) (“Successful drug development requires satisfying a matrix of domains from relevance to the disease and the drug-ability of the target through feasibility and convenience of drug delivery, demonstration of favorable benefit-risk profile in order to achieve a drug label that reflects physician and patent acceptance.") The Examiner finds that one of ordinary skill in the art would agree with the statements in these articles; that is, the amount of experimentation required to enable a pharmaceutical drug is extensive.
The level of skill in the art - the level of ordinary skill in the art may be found by inquiring into: (1) the type of problems encountered in the art; (2) prior art solutions to those problems; (3) the rapidity with which innovations are made; (4) the sophistication of the technology; and (5) the education level of active workers in the field. Custom Accessories, Inc. v. Jeffrey-Allan Industries, Inc., 807 F.2d 855, 962 (Fed. Cir. 1986). All of those factors may not be present in every case, and one or more of them may predominate. Envtl. Designs, Ltd. v. Union Oil Co., 713 F.2d 693, 696 (Fed. Cir. 1983).
Based on the typical education level of the active workers in the field of pharmaceuticals and/or medicine, as well as the high degree of sophistication required to solve problems encountered in the art, the Examiner finds that a person of ordinary skill in the art would have at least a college degree in a field related to medicine and/or the pharmaceutical art and at least four years of work experience, i.e. a masters or doctorate level scientist/clinician.
Therefore, claims 1-14 are rejected because the Examiner finds that the Wands factors suggest a conclusion that the skilled artisan would not be able to make and use the instant invention without undue experimentation, although the level of skill for an ordinary person in the art is high. That is, due to the breadth of the claims, the unpredictability of the art, the lack of guidance or direction from the disclosure, the lack of any working examples, and the amount of experimentation needed illustrate that a person having ordinary skill in the art would not be able to treat or prevent all RNA viral diseases and/or their co-infection with a bacterial infection.
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 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.
Claim(s) 1-3 and 8-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pleschka et al. (WO2014056894A1) in view of LoRusso et al. (J. Clinical Oncology.2005;23(23):5281-5293).
Regarding claim 1, Pleschka discloses a method of treating a viral disease comprising administering a MEK inhibitor (claim 1).
Pleschka does not teach PD-0184264 as a MEK inhibitor, however Pleschka teaches CI-1040.
LoRusso teaches that PD-0184264 is the active metabolite of CI-1040, with most of CI-1040 quickly converting to PD-0184264 demonstrated by the significantly higher plasma concentrations of PD-0184264 (page 5287 or Tables 3 and 4).
It would be prima facie obvious to one of ordinary skill in the art that the active metabolite of a known MEK inhibitor taught to treat viral infections would also treat the same viral infections. The pharmacokinetic profile presented by LoRusso would guide the skilled artisan to administering just the active metabolite PD-0184264.
Regarding claim 2, Pleschka discloses the method of treating a negative strand RNA virus (claim 2).
Regarding claim 3, Pleschka discloses the method of treating any viral disease, which would include positive strand RNA viruses (claim 1).
Regarding claim 8, Pleschka discloses the method of treating a viral disease comprising administering a MEK inhibitor and a neuraminidase inhibitor (claim 5).
Regarding claim 9, Pleschka discloses the neuraminidase inhibitor is selected from oseltamivir, oseltamivir phosphate, zanamivir or peramivir (claim 7).
Regarding claim 10, Pleschka discloses the method where the subject is human (paragraph [0042]).
Regarding claim 11, Pleschka discloses the method where the MEK inhibitor is administered orally (paragraph [0043]).
Regarding claims 11 and 12, Pleschka discloses the dose of 25 mg/kg (paragraph [00172]).
Regarding claim 14, Pleschka discloses administering two MEK inhibitors (paragraph [00172]).
Regarding claim 15, Pleschka discloses the pharmaceutical composition comprising a MEK inhibitor (paragraph [0044]).
Regarding claim 16, Pleschka discloses the composition can be administered orally, intravenously, intrapleurally, intramuscularly, topically or via inhalation (paragraph [0043]).
Regarding claim 17, Pleschka discloses the composition may be formulated as a tablet, capsule, chewing gum, wafer (paragraph [00125]), nasal spray or suppository (paragraph [0058]).
Regarding claim 18, Pleschka discloses the composition formulation can be a sterile injectable preparation, suspension, sterile injectable aqueous preparation (paragraph [0058]), or an elixir (paragraph [00125]).
Regarding claim 19, Pleschka discloses the dose of 25 mg/kg (paragraph [00172]).
Regarding claim 20, Pleschka discloses the dose of the MEK inhibitor can be 0.1 mg to 2000 mg (paragraph [00127]).
Claim(s) 1-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pleschka et al. (WO2014056894A1) in view of LoRusso et al. (J. Clinical Oncology.2005;23(23):5281-5293) and in further view of Ehrhardt et al. (WO2015173788A1).
The teachings of Pleschka and LoRusso are disclosed above and incorporated by reference herein.
Regarding claim 4, the combined teaching of Pleschka and LoRusso does not teach a method of treating or preventing a co-infection in a subject where the co-infection is a bacterial infection and an RNA virus infection.
Ehrhardt discloses a method of administering a MEK inhibitor for the prophylaxis and/or treatment of a co-infection comprising a bacterial infection and an influenza virus infection (claim 1). Additionally Erhardt discloses CI-1040 as the MEK inhibitor (claim 6).
In KSR International Vo. V. Teleflex Inc., 82 USPQ2d (U.S. 2007), the Supreme Court particularly emphasized “the need for caution in granting a patent based on a combination of elements found in the prior art,” (Id. At 1395) and discussed circumstances in which a patent might be determined to be obvious.
In this case at least prong A of KSR applies – combining prior art elements. It would be prima facie obvious to one of ordinary skill in the art to combine the teaching of Pleschka, LoRusso, and Erhardt and arrive at the instant invention. Pleschka teaches CI-1040 in the treatment of viral infections. Erhardt teaches CI-1040 in the treatment of bacterial and influenza co-infections. LoRusso teaches PD-0184264 as the active metabolite of CI-1040. Substitution of the method taught by Erhardt, for that taught by Pleschka is obvious as they use the MEK inhibitor, CI-1040, for the treatment of an RNA virus. LoRusso then guides the skilled artisan to the substitution of PD-0184264 for CI-1040 as it is demonstrated CI-1040 is quickly metabolized to PD-0184264.
Thus, all of the elements of claims were known to one of ordinary skill in the art at the time the invention was made and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art at the time of invention. Therefore, the claimed invention, as a whole, would have been obvious to one of ordinary skill in that art at the time the invention was made.
Regarding claim 5, Erhardt discloses the bacteria is selected from the group Staphylococcaceae, Streptococcaceae, Legionellaceae, Pseudomonadaceae, Chlamydiaceae, Mycoplasmataceae, Enterobacteriaceae, Pseudomonadales and/or Pasteurellaceae (claim 3).
Regarding claim 6, Erhardt teaches the negative RNA strand virus, influenza (claim 1).
Regarding claim 7, Pleschka discloses the method of treating any viral disease, which would include positive strand RNA viruses (claim 1).
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.
Claims 1-2, 4-6, and 8-13 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3, 6-11, 15, and 18 of U.S. Patent No. US11903917B2. Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 1 and 2, the patent discloses a method of treating influenza virus, a negative strand RNA virus, infection comprising administering an effective amount of PD-0184264 (claim 3).
Regarding claim 4, the patent discloses a method of treating a co-infection where the subject is infected with a bacterial infection and an influenza virus infection comprising administering an effective amount of PD-0184264 (claim 15).
Regarding claim 5, the patent discloses the method where the bacterial infection is mediated by Staphylococcaceae, Streptococcaceae, Legionellaceae, Pseudomonadaceae, Chlamydiaceae, Mycoplasmataceae, Enterobacteriaceae, Pseudomonadales and/or Pasteurellaceae (claim 18).
Regarding claim 6, the patent discloses a negative strand RNA virus (claim 15).
Regarding claim 8, the patent discloses the method of co-administering PD-0184264 and a neuraminidase inhibitor (claim 6).
Regarding claim 9, the patent discloses the method where the neuraminidase inhibitor is oseltamivir, oseltamivir phosphate, zanamivir, laninamivir or peramivir or a pharmaceutically acceptable salt thereof (claim 7).
Regarding claim 10, the patent discloses the method where the subject is human (claim 8).
Regarding claim 11, the patent discloses where PD-0184264 is administered orally (claim 9).
Regarding claim 12, the patent discloses the method where PD-0184264 is administered orally at a dose of 10 to 100 mg/kg (claim 11).
Regarding claim 13, the patent discloses the method where PD-0184264 is administered orally in a dosage of 2.8 mg/kg or greater (claim 10).
Claims 1-2 and 10-11 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, and 10 of U.S. Application No. 17/767,186, of which a notice of allowance has been issued but a U.S. Patent No. has not been assigned. Although the claims at issue are not identical, they are not patentably distinct from each other as the patent is a narrower scope of the instant invention. The reference claims are from the 03 February 2026 claim set.
Regarding claim 1, the patent discloses the method of treating or preventing hantavirus comprising administering PD-0184264 (claim 1).
Regarding claim 2, the patent discloses the method of treating or preventing hantavirus, a negative strand RNA virus infection (claim 1).
Regarding claim 10, the patent discloses the subject is human (claim 4).
Regarding claim 11, the patent discloses the oral administration of PD-0184264 (claim 10).
Conclusion
Claims 1-20 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jerica K Wilson whose telephone number is (703)756-4690. The examiner can normally be reached Monday-Friday 9:00-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Clinton Brooks can be reached at (571)270-7682. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.K.W./Examiner, Art Unit 1621
/CLINTON A BROOKS/Supervisory Patent Examiner, Art Unit 1621