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 .
Election/Restrictions
Applicants’ election without traverse of Group I, claims 31-35 in the reply filed on 4/9/26 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 36-50 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 4/9/26.
Applicant’s election without traverse for the SPECIES in the reply filed on 4/9/26 is acknowledged, this election stated as “(1) caspofungin derivative having an azide moiety comprising 3-azide propylamine (e.g., as in claim 33)”. A caspofungin derivative of claim 33 depending from claims 32 and 31 requires that such elected caspofungin derivative a) comprises a modified phenol, b) has anti-fungal activity, and c) wherein the modified phenol comprises an azide moiety that comprises the so-elected 3-azide propylamine. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
As understood by the examiner, 3-azide propylamine corresponds to CAS Number 88192-19-2 and has the chemical structure:
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. This is not found in any of the compounds specifically set forth in claim 34.
Claim 34 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 4/9/26.
Claim Status
Claims 31-50 are pending.
Claims 1-30 are cancelled.
Claims 36-50 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 4/9/26.
Claim 34 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 4/9/26.
Claims 31-33 and 35 are pending and under examination.
Claims 31-33 and 35 are rejected.
Priority
The instant application, filed 02/06/2023 is a Continuation of PCT/IL2021/050990 , filed 08/15/2021
18106009 Claims Priority from Provisional Application 63066407 , filed 08/17/2020.
Information Disclosure Statement
The Examiner has considered the reference(s) provided in the 3/8/23 Information Disclosure Statement, and provides a signed and dated copy of such herewith.
Specification
The disclosure is objected to because of the following informalities: the line quality of Compounds is too faint for the compounds depicted after paras 83, 87, 90, 91.
Appropriate correction is required.1
Claim Interpretation
The claim limitations are given their broadest reasonable interpretation (BRI) consistent with the specification, MPEP 2111, and under the BRI, words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification, MPEP 2111.01.
The transitional term “comprising” is inclusive or open-ended and does not exclude additional, unrecited elements. See MPEP 2111.03.
Neither “Derivative”, especially of caspofungin given its relevance to the breadth of the claims, nor “caspofungin derivative” are defined in the application as filed.
“Derivative” in the chemical arts is defined as
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, see screen shot of Merriam-Webster online dictionary, provided.
Based on such definition, which includes parts a and b, a “caspofungin derivative” encompasses any compound that can be made from it. Claim 31 however requires that such caspofungin derivative comprises a modified phenol and that such caspofungin derivative has anti-fungal activity, which is interrupted broadly so that any amount of anti-fungal activity against any one fungus species satisfies this limitation.
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 31-33 and 35 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) 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, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Regarding claims 32 and 33:
The transitional term “comprising” is defined above with regard to claim usage. However, further to the basic usage of “comprising”, the specific component, article, moiety set forth in the claim that the claim states after “comprising” must be present in what is claimed. From the examiner’s analysis this is not the case for azide moiety, nor particularly the elected 3-azide propylamine.
Figure 1 and accompanying text in the specification bear this out. Per para 122, after confirming the structure of Compound 1a (which comprises a propargyl reactive group), “Finally, azide functionalized tetramethylrhodamine (TMR) and nitrobenzoxadiazole (NBD) dyes (FIG. 1A) were coupled with Compound 1a under the click reaction conditions to produce fluorescent caspofungin probes 1 (61% isolated yield; absorption-550 nm and emmision-585 nm) and 2 (68% isolated yield; absorption-470 nm and emmision-540 nm), respectively.” Regardless of whether or not either or both of the azide functionalized dyes comprised 3-azide propylamine, the resultant Compounds 1 and 2 did not. There is no other example or basis for possession of what is claimed that truly, after reaction, comprises 3-azide propylamine.
Nor, expanding to the broader limitation of azide moiety in claim 32, is there any support for a final product caspofungin derivative described and/or depicted in the application as filed to comprise an azide moiety. The examiner notes that a 1,2,3-triazole ring resulting from a Click Chemistry reaction does not comprise an azide.
Based on the above, claims 32 and 33 are rejected based on lack of possession for what is claimed therein.
Additionally, and further with regard to directly bonding to the tyrosine hydroxyl group, it is the examiner’s understanding that this is not favored, at least for 3-azido propylamine, because the unmodified phenolic oxygen is an inefficient nucleophile. The examiner has not identified language or syntheses regarding adding linkers, which would be one approach to indirectly reacting 3-azido propylamine with the hydroxyl of the phenol.
Claims 31-33 and 35 separately are rejected based on lack of possession of the claimed genera of the respective claims.
The importance of sufficient representative species or structure/function correlations has been highlighted by the courts (Abbvie Deutschland v. Janssen Biotech and Centorcor Biologics, App. No. 2013-1338, -1346 (Fed. Cir. , July 1, 2014)). The Abbvie case involved antibodies and written description. The court stated: “We have held that “a sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Id. at 1350 (quoting Eli Lilly, 119 F.3d at 1568– 69).”. The courts then further stated: “With the written description of a genus, however, merely drawing a fence around a perceived genus is not a description of the genus. One needs to show that one has truly invented the genus, i.e., that one has conceived and described sufficient representative species encompassing the breadth of the genus. Otherwise, one has only a research plan, leaving it to others to explore the unknown contours of the claimed genus.” (emphasis added) and then state: " Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Ariad, 598 F.3d at 1351 (“[T]he level of detail required to satisfy the written description requirement varies depending on the nature and scope of the claims and on the complexity and predictability of the relevant technology.”); see also Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341, 1352 (Fed. Cir. 2011).
Applicant has not set forth which modifications across the genus of possible structures would retain the property of possessing anti-fungal activity.
Separately from structure/function correlations disclosed in an application, written description for a genus can be achieved by a representative number of species within a broad generic claim. It is unquestionable that claims 31-33 and 35 are broad and generic, with respect to all possible derivatives and modifications (from modified phenol) by the claims. Here, with 3 examples constructed and evaluated, the specification lacks sufficient variety of species to reflect this variance in the genus. The specification does not provide sufficient descriptive support for the myriad of diverse species embraced by the claims.
More specifically to this point, Applicant depicts and teaches 3 compounds – 1a (which also can be considered a reactive substrate or intermediate, reacting upon combining with an azide-comprising moiety of a second compound), and 1 and 2, each having a dye molecule attached via a “Click Chemistry-reacted” portion comprising a 1,2,3-triazole ring). Given the breadth of “derivative”, and also the multiple locations on the benzene to which any of a wide range of diverse modifications can be made, these falling within the claims’ “modified phenol” – see for example the multiple moieties attached in Black et al., Bioorganic & Medicinal Chemistry, Letters, Vol. 7, No. 22, pp. 2879-2884, 1997, see Tables 1 and 2, dealing with moieties mostly (all but compound 3a) only at one position on the benzyl ring (and these moieties themselves not representative of type of molecules that can be added to modify the phenol), and the application as filed lacking sufficient guidance, structure/function relationships, or other examples sufficient for the breadth of what is encompassed by claim 31 and claims 32, 33 and 35 under examination, the examiner concludes that there are insufficient species representative of the respective genera of these claims to indicate possession of the invention. The examiner notes that Black, page 2883, states that “Severe steric bulk around the phenol is not well tolerated,” this reasonably related to the requirement for the phenolic hydroxyl to bind into a pocket of the fungal enzyme 1,3-B-(D) glucan synthase, the enzyme blocked by this class of compounds (see also Introduction, page 2879). In the instant case, applicant has not provided teachings, examples, structure/function correlations, or other support for showing possession of a genus of compounds comprising a modified phenol of a caspofungin derivative that retains anti-fungal activity, this is at least because one of ordinary skill in the art could not visualize or recognize a sufficient number of species representative of the claimed genus – that genus inclusive of diverse modifying moieties, at any of one or more positions of the phenol, that would still possess the claimed anti-fungal activity.
The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals Appellant hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention of claims 31-33 and 35.
Claim Rejections - 35 USC § 102
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 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(s) 31 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Black et al., Bioorganic & Medicinal Chemistry, Letters, Vol. 7, No. 22, pp. 2879-2884, 1997 (“Black”).
For compact prosecution, this rejection expands beyond the elected species.
Black teaches modifications of the phenol, mostly at the 3’ position, of two closely related cyclic hexapeptides – pneumocandin B0 and its dideoxy analog, having similarities in structure with caspofungin, so absent evidence to the contrary each of these is a chemical compound that can be made from caspofungin (as can all of the evaluated variants in Black), so these are encompassed by the term “caspofungin derivative”.
Most of the phenol-modified variants/derivatives demonstrate anti-fungal activities for at least one species, so meet the claim 31 requirement for having anti-fungal activity, see Tables 1 and 2.
Accordingly, claim 31 is anticipated by Black’s species that both comprise a modified phenol and demonstrate anti-fungal activity (all in Table 1 except compounds 6, 16b and 16c, and all in Table 2).
Claim(s) 31 and 35 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US Patent No. 6384013, Burkhardt et al., issued 5/7/2002 (Burkhardt)
For compact prosecution, this rejection expands beyond the elected species.
Burkhardt teaches multiple chemical structures that have structural similarities to caspofungin, see Formula (1) and claims 1-6, so absent evidence to the contrary these are chemical compounds that can be made from caspofungin, so these are encompassed by the term “caspofungin derivative”.
Burhardt teaches a modified phenol on one of its claimed compounds, claim 6, see also columns 53-60.
Burkhardt teaches that its acylated cyclic hexapeptides having unique side chain acyl groups which, inter alia impart enhanced antifungal and antiparasitic potency e.g. against pathogenic strains of Candida albicans, para 5, so the resultant compound(s) with the modified phenol have anti-fungal property at that is interpreted.
Accordingly, Burkhardt anticipates claim 31.
Burkhardt also anticipates claim 35 based on its teachings of combining a compound of formula 1 (which encompasses the species set forth in the specification and claims) with a physiologically acceptable diluent such as deionized water, physiological saline, 5% dextrose and other commonly used diluents, for parenteral administration formulation (clearly a pharmaceutical composition), as well as with excipients, such as in a sterile vial with an antifungal, and for tablets, para 170, so anticipates claim 35.
Prior Art Made of Record
The prior art made of record and not relied upon in instant rejections is considered pertinent to applicant's disclosure. US 20170355730 A1, Pei and Qian, published 12/14/2017, para 348, teaches labeling a bicyclic peptide on each bead with tetramethylrhodamine (TMR) azide at the Pra residue (this is L-propargylglycine) and releasing from the bead by treatment with a NaOH solution. BroadPharm web page, 2022 (so not prior art, but supportive, evidentiary), depicts a linker of TAMRA azide, 5-isomer (which the examiner understands is synonymous for a tetramethylrhodamine (TMR) azide), and teaches that this “is a linker of TAMRA which is a xanthine dye with orange emission. The addition of the azide groups allows for it to be reactive with alkynes, DBCO and BCN for copper-catalyzed Click Chemistry.” The structure of TAMRA azide, 5-isomer:
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comprises HN(CH2)3N3, a bonded form of 3-azide propylamine, which resembles the azide moiety applicant claims in claim 33, which however does not remain in such form after reaction with a group such as a propargyl group (instead forming a ring per Click Chemistry).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH FISCHER whose telephone number is (571)270-7925, and whose direct facsimile number is (571)270-8925. The examiner can normally be reached on Monday to Friday, 9:00 AM to 5:00 PM, however noting that the examiner will not normally be working on Monday/Tuesday and on Wednesday-Friday on alternating weeks, but will promptly answer messages upon his return to work.
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, Melissa Fisher can be reached on 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JOSEPH FISCHER/Primary Examiner, Art Unit 1658
1 As a courtesy, although claim 34 is not under examination, the examiner points out that the lines of the compounds depicted in that claim also are too light and would be objected to if under examination. Applicant may consider this when also correcting the lines of the compounds in the specification. See line representations of Figure 1A as indicative of clear, not faint, lines and letters.
Prosecution Insights