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 .
Formal Matters
Claims 1-13 were originally presented on 09/06/2022. The preliminary amendments to the claims filed 02/28/2023 have been received and entered. Claims 1-13 were cancelled and claims 14-33 newly added.
Claims 14-33 are pending and under examination.
Priority
This application is a national-stage application under 35 U.S.C. § 371 of International Application No. PCT/EP2021/055504, filed March 4, 2021, which International Application claims benefit of priority to Great British Patent Application No. 2003240.5, filed March 5, 2020.
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
Applicant’s Information Disclosure Statement filed 12/05/2022 has been received and entered into the present application. As reflected by the attached, completed copy of form PTO-1449, the Examiner has considered the cited references to the extent that they comply with the provisions of 37 C.F.R. §1.97, §1.98 and MPEP §609.
Claim Rejections - 35 USC § 112(b)
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.
"The primary purpose of this requirement of definiteness of claim language is to ensure that the scope of the claims is clear so the public is informed of the boundaries of what constitutes infringement of the patent. A secondary purpose is to provide a clear measure of what applicants regard as the invention so that it can be determined whether the claimed invention meets all the criteria for patentability and whether the specification meets the criteria of 35 U.S.C. 112, first paragraph with respect to the claimed invention.", (see MPEP § 2173).
Claims 14-28 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.
For variable substituent Z the claim recites “(hetero)aryl”, which renders the claims unclear whether the parenthetical information “hetero” is a claim limitation. In this case, Applicants do not define the term “(hetero)aryl” which renders the scope of this term subjective, i.e., whether it is limited to a heteroaryl or if “hetero” is optional.
The Examiner suggests amending the claim to remove recitation of the parentheses if it is Applicants’ intent that Z is limited to a heteroaryl group. If Z is intended to be a heteroaryl group OR an aryl group, these claim terms should be separately recited, i.e., “…an unsubstituted heteroaryl group or an unsubstituted aryl group…”.
Claim Rejections - 35 USC § 112(a) (Enablement)
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 14-28 and 32-33 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 different salts of myramistin (i.e., replacing the chloride anion with other anions) and derivatives of myramistin wherein the unsubstituted benzyl group is replaced with substituted benzyl groups, 2-naphthyl, ethylphenyl, or a thiophene group, does not reasonably provide enablement for other compounds of formula (I). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
To be enabling, the specification of the patent application 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 that:
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 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).1
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 (CAFC 1988) at 1404 wherein, citing Ex parte Forman, 230 USPQ 546 (Bd. Apls. 1986) at 547 the court recited eight factors:
1) the quantity of experimentation necessary,
2) the amount of direction or guidance provided,
3) the presence or absence of working examples,
4) the nature of the invention,
5) the state of the prior art,
6) the relative skill of those in the art,
7) the predictability of the art, and
8) the breadth of the claims.
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 and breadth of the claims
The invention is drawn to a method for treatment of infections caused by an enveloped virus in a subject, the method comprising administering to the subject a therapeutically effective amount of a compound of formula (I):
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See Claim 14.
The claims thus encompass the treatment of infections caused by any and all enveloped viruses, e.g., influenza, HPV, HIV, adenoviruses, and coronaviruses, comprising the administration of any and all compounds falling within the broad scope of the claimed formula (I). The genus of formula (I) is immense, likely encompassing hundreds of thousands of structurally diverse species.
The state and predictability of the art, and relative skill of those in the art
The only compound of formula (I) known in the art to have activity against enveloped viruses is myramistin, which is the species that Applicants expressly exclude from their claims. As such, the structure/activity relationship for compounds of formula (I) has not been established in the art for antiviral activity. A person of ordinary skill in the art would therefore not be able to predict with any reasonable certainty whether any given compound of formula (I) other than myramistin would be expected to antiviral activity against enveloped viruses. Indeed, the 13 species tested by Applicants, including myramistin, had minimal antiviral activity against an undescribed virus in vitro (Specification at p.37). For example, the L-lactate salt of myramistin had 0% inhibition at 14 mM and only 18.5% inhibition at 29 mM, concentrations unlikely to be achieved in a subject. Confusingly, while n-propyl, 2-napthyl, and 3-methyl derivatives of myramistin showed some antiviral activity at 14 mM (21.4%, 45.4%, and 20.3%, respectively), they showed 0% inhibition at a higher concentration (29 mM).
The closest prior art is RU 2234313 C1, which disclosed the use of myramistin (myristamidopropyldimethylbenzyl ammonium chloride) in the treatment of diseases of respiratory ways caused by coronaviruses. This species is excluded from Applicants’ claims. Applicants made and tested four different salts of myramistin and substituted benzyl derivatives thereof.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification 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, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed most recently in Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v. Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008). See also In re Cortright, 49 USPQ2d 1464, 1466 and Bristol-Myers Squibb Co. v. Rhone-Poulenc Rorer Inc., 49 USPQ2d 1370.
Here, relative to the scope of the claimed invention, the specification does not teach those skilled in the art to make and use the full scope of the invention without undue experimentation. As will be discussed in more detail below, Applicants teach simple anion replacements of myramistin, e.g., chloride to L-lactate salt, and making different substituted benzyl derivatives of myramistin. Applicants do not, however, teach how to make other species falling within the vast genus claimed.
The amount of direction or guidance provided and the presence or absence of working examples
The specification provides direction or guidance only for making and using different salts of myramistin, an ester derivative of myramistin, and substituted benzyl derivatives thereof. The compounds made and tested by Applicants comprise compounds of formula (I) wherein L1 is a C11 alkyl, X is NH, L2 is a C2 alkyl, X1 is CH2, L3 is a C2 alkyl, each R is methyl, L4 is CH2, and Z is a substituted or unsubstituted benzyl, 2-naphthyl, or thiophene. Such compounds are very narrow in scope and nowhere to commensurate in scope with the claimed genus of formula (I). The following are representative of the scope of compounds actually made and tested by Applicants:
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In distinct contrast, the claimed formula (I) encompasses innumerable compounds that are in fact not structurally closely related to myramistin.
Working examples are limited to testing the inhibitory activity of 4 different salts of myramistin and 7 derivatives of myramistin having substituted benzyl groups or the benzyl group of myramistin replaced with a 2-naphthyl, ethylphenyl, or thiophene group. These groups are not at all representative of the claimed substituted or unsubstituted “(hetero)aryl” group. Even here, the 13 species tested by Applicants, including myramistin, had minimal antiviral activity against an undescribed virus in vitro (Specification at p.37). For example, the L-lactate salt of myramistin had 0% inhibition at 14 mM and only 18.5% inhibition at 29 mM, concentrations unlikely to be achieved in a subject. Confusingly, while n-propyl, 2-napthyl, and 3-methyl derivatives of myramistin showed some antiviral activity at 14 mM (21.4%, 45.4%, and 20.3%, respectively), they showed 0% inhibition at a higher concentration (29 mM).
There is not a single working example demonstrating that any compound of formula (I) is effective in treating an infection caused by any enveloped virus in a subject as now claimed.
The quantity of experimentation necessary
Because of the known unpredictability of the art (as discussed supra) and in the absence of experimental evidence commensurate in scope with the claims, the skilled artisan would not accept the assertion that the instantly claimed genus of compounds could be predictably used as a treatment for all infections caused by all enveloped viruses in a subject as inferred in the claims and contemplated by the specification.
Genentech Inc. vs. Nova Nordisk states, "[A] patent is not a hunting license. It is not a reward for a search but a compensation for its successful conclusion and ‘patent protection’ is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable” (42 USPQ 2d 1001, Fed. Circuit 1997).
In the instant case, Applicants have presented a general idea that because myramistin is taught in the prior art to have activity in inhibiting coronaviruses then the instantly claimed compounds of formula (I) must therefore, a priori, be useful in the treatment of infections caused by all enveloped viruses in a subject. However, the claims encompass innumerable compounds having a plethora of chemically and biologically distinct substituents. Applicants synthesized numerous different salts of myramistin, i.e., replacing the chloride anion of myramistin with different anions, and a limited number of derivatives of myramistin wherein the unsubstituted benzyl group is replaced with substituted benzyl groups, 2-naphthyl, ethylphenyl, or a thiophene group.
It is evident that a very small percentage of the claimed compounds were actually synthesized and tested by Applicants and all of the synthesized compounds were closely related in structure, i.e., different salts of myramistin or derivatives of myramistin having different groups substituted for the benzyl group of myramistin. The fact remains that all compounds made by Applicants contained the general structure of myramistin, differing only in the anion or the benzyl group of myramistin.
Given the extremely diverse compounds encompassed by the claims and the limited examples provided in the specification, the skilled artisan cannot predict what structural features (other than those of the compounds actually synthesized) are important for enveloped virus inhibition. In other words, the structure activity relationship demonstrated in the examples is limited to a very small sub-genus of compounds.
Determining if any particular claimed compound would treat any particular cancerous disease state would require synthesis of the compound, formulation into a suitable dosage form, and subjecting it to clinical trials or to testing in an assay known to correlate to clinical efficacy of such treatment. This is undue experimentation given the limited guidance and direction provided by Applicants. As noted supra, even in vitro and in vivo assays do not always correlate to efficacy in humans and are not generally predictive of clinical efficacy.
Accordingly, the instant claims do not comply with the enablement requirement of 35 U.S.C. § 112, first paragraph, since to practice the claimed invention a person of ordinary skill in the art would have to engage in undue experimentation, with no assurance of success.
Allowable Subject Matter
Claims 29-31 are allowed.
Conclusion
Applicant is requested to specifically point out the support for any amendments made to the disclosure in response to this Office action, including the claims (M.P.E.P. §§ 714.02 and 2163.06). In doing so, applicant is requested to refer to pages and line (or paragraph) numbers (if available) in the as-filed specification, not the published application. Due to the procedure outlined in M.P.E.P. § 2163.06 for interpreting claims, other art may be applicable under 35 U.S.C. § 102 or 35 U.S.C. § 103(a) once the aforementioned issue(s) is/are addressed.
Applicant is reminded that MPEP §2001.06(b) clearly states that “[t]he individuals covered by 37 C.F.R. 1.56 have a duty to bring to the attention of the examiner, or other Office official involved with the examination of a particular application, information within their knowledge as to other copending United States applications which are "material to patentability" of the application in question." See Armour & Co. v. Swift & Co., 466 F.2d 767, 779, 175 USPQ 70, 79 (7th Cir. 1972). MPEP §2001.06(b) clearly indicates that “if a particular inventor has different applications pending in which similar subject matter but patentably indistinct claims are present that fact must be disclosed to the examiner of each of the involved applications.” See Dayco Prod. Inc. v. Total Containment, Inc., 329 F.3d 1358, 1365-69, 66 USPQ2d 1801, 1806-08 (Fed. Cir. 2003).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAMES D ANDERSON whose telephone number is (571)272-9038. The examiner can normally be reached on Monday-Friday, 8:30 am - 5:00 pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Lundgren can be reached on 571-272-5541. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/James D. Anderson/Primary Examiner, Art Unit 1629
UNITED STATES PATENT AND TRADEMARK OFFICE
400 Dulany Street
Alexandria, VA 22314-5774
Tel. No.: (571) 272-9038
1 As pointed out by the court in In re Angstadt, 537 F.2d 498 at 504 (CCPA 1976), the key word is “undue”, not “experimentation”.