DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Claims 32-41 are pending and are rejected.
Priority
This application is a CON of 16/613,061, filed 11/12/2019 (US 11,666,559), which is a 371 of PCT/IB2018/053357, filed 05/14/2018, which claims foreign priority to Portuguese application no. 110070, filed 05/12/2017. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120 as follows:
Applicant states that this application is a continuation application of the prior-filed application. A continuation application cannot include new matter. Applicant is required to delete the benefit claim or change the relationship (continuation application) to continuation-in-part because this application contains the following matter not disclosed in the prior-filed application:
Claim 35 recites the infectious diseases human influenza B virus and Respiratory Syncytial virus type A and B, which are not recited or inherently supported in the specification or in the prior filed applications.
Applicant may also delete the new matter from claim 35 to receive the benefit of an earlier filing date.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 8/14/2023 is in compliance with the provisions of 37 CFR 1.97 and 37 CFR 1.98. Accordingly, the IDS has been considered by the examiner and a signed copy is enclosed herewith.
Claim Objections
Claim 34 is objected to for a grammatical informality; namely, the recitation of “or” in the second line of the claim, after “hepatitis D”. This objection may be overcome by deleting the conjunction. Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
The following is a quotation 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.
(1 of 2) Claim 35 is rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor at the time the application was filed, had possession of the claimed invention.
The preliminary amendment filed 4/12/2023 introduced new matter into claim 35 with reciting human influenza B viruses and Respiratory Syncytial virus type A and B. These viruses are not disclosed in the application as filed and there are no blaze marks leading a PHOSITA to these viruses.
Applicant may overcome this rejection by deleting the new matter from claim 35.
(2 of 2) Claims 32, 33 and 40-41 are rejected under 35 U.S.C. 112(a) because the specification, while being enabling for treating the infectious diseases of claims 34 and 36:
acquired immunodeficiency syndrome, malaria, hepatitis A, hepatitis B, hepatitis C, hepatitis D, hepatitis E, herpes simplex infection, human papillomavirus infection, and respiratory infections caused by viruses, human immunodeficiency virus infection or Plasmodium infection,
does not reasonably provide enablement for treating all infectious diseases. 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 Wands Factors: According to MPEP § 2164.01(a), “[t]he determination that ‘undue experimentation’ would have been needed to make and use the claimed invention is not a single, simple factual determination. Rather, it is a conclusion reached by weighing all the above noted factual considerations. In re Wands, 858 F. 2d at 737, 8 USPQ2d at 1404.” “These factors include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure.”
Breadth of the Claims
“The more one claims, the more one must enable.” Amgen Inc. v. Sanofi, 598 U.S. 594, 610 (2023) (citing Incandescent Lamp, 159 U. S. 465, 475, 16 S. Ct. 75, 40 L. Ed. 221 (1895)). Claims 32, 33 and 40-41 recite a method of treating “infectious diseases” (claim 32), “caused by pathogenic agents selected from a virus, a protozoan, and mixtures thereof” (claim 33). The method comprises administering a composition comprising a spiro-lactam compound of claim 32, wherein the composition may further comprise:
“an additional active ingredient [] [that] is a HIV protease inhibitor (PI), a HIV nucleoside reverse transcriptase inhibitor (NRTI), a HIV nonnucleoside reverse transcriptase inhibitor (NNRTI), a HIV integrase inhibitor, a HIV entry inhibitor, or mixtures thereof” (claim 40), or
“an antiviral agent, an anti-malarial agent, an immunomodulator agent, an analgesic
agent, an anti-inflammatory agent, an antibiotic agent or a diuretic agent” (claim 41).
Since the claims embrace a massively wide and diverse scope of infectious diseases, the claims are extraordinarily broad.
Nature of the Invention and State of the Prior Art
The compositions administered require spiro-β-lactam compounds, such as
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, which are spiro-derivatives of penicillin,
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. Penicillin and its β-lactam derivatives are known in the art as antibiotics “that interrupt bacterial cell-wall formation as a result of covalent binding to essential penicillin-binding proteins (PBPs), enzymes that are involved in the terminal steps of peptidoglycan cross-linking in both Gram-negative and Gram-positive bacteria.” Bush et al. Cold Spring Harb. Perspect. Med. 2016;6:a025247 at p. 2. “PG is unique to the bacterial kingdom, and its synthesis is the
target of the most clinically important antibiotics ever discovered such as the beta-lactams (penicillin) and glycopeptides (vancomycin).” Bern et al. Anal. Bioanal. Chem. 2017, 409, 551-560 at 551 (right column).
Level of Predictability in the Art
“The ‘predictability or lack thereof’ in the art refers to the ability of one skilled in the art to extrapolate the disclosed or known results to the claimed invention” (MPEP § 2164.03). It is well-known that “[a]ntibiotics are ineffective against viral infections” and cannot be used to treat illnesses caused by viruses. Carlet et al., Antimicrob. Resist. Infect. Control 2012, 1:11 at p. 7.
The clinical failure of antibiotics extends to protozoan treatments as well. Beta-lactams, like penicillin, “specifically target[] bacteria, as eukaryotic cells lack both PGN [peptidoglycan] and the enzymes responsible for PGN synthesis.” Lobanovska, et al. Yale J. Biol. Med., 2017, 90, 135-145 at 138 (left column). Since protozoa are eukaryotic organisms, they inherently lack the biological targets of beta-lactams.
Because viruses and protozoans completely lack the peptidoglycan target that β-lactams are known to inhibit, treating viral or protozoan diseases using the claimed β-lactam compounds would be unpredictable if not unsuccessful.
Direction Provided by the Inventor and Working Examples
The specification states that the spiro-lactam compounds are “anti-HIV/AIDS and anti-malarial agents,” which is supported by IC50 data. Spec. ¶ 1 and Figures 3, 6, 7 and 8, for example. There is no data or guidance provided that supports using the compounds for other infectious diseases.
Quantity of Experimentation
To practice the full scope of treating all viral or protozoal infections with the claimed spiro-beta-lactams, a PHOSITA would test innumerable viral and protozoal diseases and compound combinations in search of an effective treatment combination. Therefore, considering the immense breadth of the viral and protozoal genera, the inherent lack of a shared peptidoglycan target for the claimed beta-lactams, and the highly unpredictable nature of the art, claims 32, 33, and 40-41 require a PHOSITA to engage in undue experimentation and fail to satisfy the enablement requirement of 35 U.S.C. § 112(a). This rejection may be overcome by limiting the diseases to those of claims 34, 35 and/or 36.
Claim Rejections - 35 USC § 102
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.
Claim 35 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bartolo, et al. ACS Infect. Dis. 2021, 7, 421-434.
Bartolo teaches spiro-lactams BSS-730A and BSS-722A are lead compounds that “exhibited potent activity against all HIV-1 and HIV-2 isolates (Figure 3B,C).” Bartolo 423 (right column). “Thus, these new spiro-β-lactams or variations thereof may be particularly useful to treat or prevent infections by HIV-1, HIV-2, and drug-resistant isolates that are emerging [].”
Bartolo 426 (right column).
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BSS-730A and BSS-722A also displayed antiplasmodial activity against P. berghei hepatic infection. BSS-730A further displayed activity against the human P. falciparum parasite. Bartolo 425 (right column). Bartolo concludes “BSS-730A is a promising candidate for development as a potential therapeutic and/or prophylactic agent against HIV and Plasmodium.” Bartolo 428 (left column).
Based on Bartolo’s teaching, a PHOSITA would at once envisage treating a human HIV- or Plasmodium-infected patient infected by administering a composition comprising BSS-730A or BSS-722A (the latter for HIV-1 and HIV-2 only). This anticipates the claimed treatment method of administering the compound
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(claim 32, line 7) or
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(claim 32, line 8), according to instant claim 35.
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 32-41 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11,666,559.
Although the claims at issue are not identical, they are not patentably distinct from each other because claims 1-11 of the ‘559 patent disclose the compounds
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,
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and
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(e.g., claim 1) in the form of a pharmaceutical composition (e.g., claim 5),
“wherein the compound exhibits inhibitory activity against human immunodeficiency
virus (HIV) and Plasmodium species”, such as HIV-2 group A (claims 2-3, which render obvious instant claims 32-38),
wherein the Plasmodium species is Plasmodium falciparum, for example (claim 4, rendering obvious instant claim 39), and
wherein the composition further comprises a carrier and a second active (claim 5), such as an antiviral agent (claim 6, rendering obvious instant claim 41), “wherein the antiviral agent is an anti-HIV agent” (claim 7), such as a HIV integrase inhibitor (claim 9, rendering obvious instant claim 40).
Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMANDA L AGUIRRE whose telephone number is (571)272-5592. The examiner can normally be reached 10 am-6 pm MST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, JEFFREY H MURRAY can be reached on 571-272-9023. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/AMANDA L. AGUIRRE/ Primary Examiner, Art Unit 1626
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