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 Claims
Claims 1-23 are pending.
Information Disclosure Statement
The information disclosure statement filed 12-31-2024 has been considered. An initialed copy is enclosed.
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 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.
Claims 1-23 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 a compound where R1 and R2 are acetyl and n is about 4 to about 20, compositions comprising such in an adjuvant, carrier, excipient or buffer and the composition comprising the compound in methods for raising an immune response or inhibiting the growth of pseudoaminic acid-bearing Acinetobacter spp.and Acinetobacter baumannii strains, it does not reasonably provide enablement for any method of use for the compound where R1 and R1 are independently formyl or ( R)-3-hydroxybutyryl where n is 0-3. 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.
The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: 1) scope or breadth of the claims; 2) nature of the invention; 3) relative level of skill possessed by one of ordinary skill in the art; 4) state of, or the amount of knowledge in, the prior art; 5) level or degree of predictability, or a lack thereof, in the art; 6) amount of guidance or direction provided by the inventor; 7) presence or absence of working examples; and 8) quantity of experimentation required to make and use the claimed invention based upon the content of the supporting disclosure. When the above factors are weighed, it is the Examiner’s position that one skilled in the art could not practice the invention without undue experimentation.
While all of the factors have been considered, only those deemed necessary to establish a prima facie case are set forth below.
Scope or breadth of the claims
The instant claims are broadly drawn to conjugate compounds where at least one pseudaminic acid (Pse) moiety is conjugated where the conjugate has the following structure
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where R1, R2 and n are undefined and in dependent claims R1 and R2 are independently defined as acetyl, formal and hydroxybutyryl and n is about 4 to about 20, compositions comprising the compound in an adjuvant, carrier, excipient or buffer and the composition comprising the compound in methods for raising an immune response or inhibiting the growth of Acinetobacter spp.and Acinetobacter baumannii strains bearing Pse. The compounds as disclosed are said to be useful as immunogens against Acinetobacter spp and Acinetobacter baumannii strains in particular that bear pseudaminic acid.
Knowledge of the prior art
The prior art teaches other glycoconjugate vaccines, their preparation and methods of use thereof, where the terminal pseudaminic acid induces antibodies that mediate the protective immune response of the conjugate (see Wu et al (US 2020/0179503, June 11, 2020)) abstract and claims. Wu et al teach that the Pse plays a critical role in antigenicity and that the specificity of the antibody recognition is attributed to the structural differences between Pse and sialic acid of the N-acetyl group on C7 and hydroxyl group on C9 (see page 12, Example 2, paragraph [0093]). The antibodies produced in response to the conjugate provided for bacterial cell killing (see Figure 2; pages 3-4; paragraph [0038]).
Guidance provided by inventor/working examples
The specification demonstrates that Formulas set forth in claim 15 provide for an immune response when administered with adjuvant and that the immune response inhibits the growth of Acinetobacter baumannii strains in particular that bear pseudaminic acid.
The specification and art do not demonstrate a similar immune response using substitutions of R1, R1 by the claimed formyl and hydroxybutyryl and the number of linked monomers has not been fully demonstrated for the scope. None of the other substituent variants have been tested for efficacy in generating an immune response that binds Acinetobacter spp that bear pseudaminic acid.
Level or degree of predictability
The structure that correlates with the immune response on the bacterium is the pseudaminic acid and such a correlation is known to the art (see Lee et al, (J. Am. Chem. Soc, 140:8639-8643, 2018; of record and Wu et al supra) which establishes that pseudaminic acid plays a critical role in recognition of glycoconjugate boosted serum (see paragraph bridging pages 8641-8642).
The cross-reactivity of antibodies raised against the other potential compounds (instantly claimed R1 and/or R2 with formyl or hydroxybutyryl with pseudaminic acid bearing spp has not been demonstrated. It is noted that the skilled artisan defines a cross-reacting antibody is an antibody capable of binding to an antigen which did not specifically stimulate its production. Depending on the presence and distribution of epitopes this cross reaction may not be as strong as the reaction of the antibody with its own antigen although in some cases it can be stronger (see Herbert et al, The Dictionary of Immunology, Fourth Edition, Academic Press Inc. ,page 49, 1995). Antibody cross-reactivity is inherently an unpredictable event and Applicant has not demonstrated that antibodies generated in response to non-acetyl variants of the claimed compound, bind to Pse-bearing Acinetobacter. Moreover, the ability of antibodies to discriminate between related structures is well established in the art. Berzofsky et al in Fundamental Immunology (Paul ed, Raven Press Inc,1989, pages 169-176; page 170 Table 1 and associated text) teach antibody binding demonstrates specificity even among highly related structures. The specification does not teach that antibodies raised to the formyl and hydroxybutryryl substituent R1 and R2 variants bind Acinetobacter spp that bear pseudaminic acid. Absent binding Acinetobacter spp that bear pseudaminic acid, the specification provides for no particular use for the claimed conjugates. Mere raising of an immune response is not a particular use that is specific to the structure and is merely an activity that can be imputed to any administered structure and does not demonstrate that the antibodies would have activity against Pse-bearing Acinetobacter spp and Acinetobacter baumannii in particular.
Quantity of experimentation
While the skill in the art is high, the skilled artisan would have to design a chemical synthesis for the structures, make the conjugates, purify the conjugates and perform in vitro and in vivo testing to determine if the immune response or antibodies produced therefrom are useful. Given the known specificity of antibodies for the Pse structure in the art, it is unpredictable that such variant structures would provide for binding. The courts have held that the disclosure is insufficient when testing is necessary to determine the actual use or possible lack of use (In re Kirk and Petrow 153 USPQ 48 (CCPA 1967). In applications directed to inventions in arts but where the results are unpredictable, the disclosure of a single species usually does not provide an adequate basis to support generic claims. In re Soll, 97 F.2d 623, 624, 38 USPQ 189, 191 (CCPA 1938). In cases involving unpredictable factors, such as most chemical reactions and physiological activity, more may be required. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970) (contrasting mechanical and electrical elements with chemical reactions and physiological activity). See also In re Wright, 999 F.2d 1557, 1562, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993); In re Vaeck, 947 F.2d 488, 496, 20 USPQ2d 1438, 1445 (Fed. Cir. 1991). This is because it is not obvious from the disclosure of one species, what other species will work.
In light of the foregoing factors, the evidence as a whole suggests that the specification, in light of the level of knowledge in the art, does not enable one of ordinary skill to make or use the invention over the full scope of the instant claims without undue experimentation. Consequently, the claims are prima facie non-enabled for their scope.
Claims 1-14 and 16-23 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
As to claim 1, the claim is prima facie indefinite in that it does not define variable substituents “R1”, “R2” and “n” such that the skilled artisan would be unable to understand the meets and bounds of the structure set forth in the claim. Since any one of dependent claims 2-14 and 16-23 do not define all three variables, they are likewise rejected.
As to claims 1-14 and 16-23, the claims are prima facie indefinite from the use of the term “about” with respect to chemical structures comprising specific number of atoms. The term about generally means latitude above and below the specific number, however atoms do not appear in fractions and as such, it is unclear what Applicant intends by “about” when representing the number of atoms in a chemical structure. Additionally with respect to “about O”, how do you get a structure with less than the number of atoms depicted in the chemical structure ? Correction is required.
As to claim 15, the claim is confusing using the fractional representation of ‘n’. “n” cannot be a fraction, either the glycol-linker-connector is present in the compound or not. “n” by definition should be a whole integer. The claims are drawn to compounds not compositions that may represent the average of different conjugates each having varying degrees of substitution. Thus, in a composition ‘n’ may represent the average number of the conjugated in the composition which may be a non-integer. However, this is not the case here.. a specific compound is being claimed. Correction is required.
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.
Claims 1-7 and 16-23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wu et al (US 2020/0179503, June 11, 2020).
Wu et al teach the conjugate
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The terminal Pse is circled (see abstract and page 1, Formula I). The remainder of the molecule
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Wu et al teach a glycoconjuge vaccine that is characterized in having homogenous microbial oligosaccharide fragments covalently linked to a carrier protein. Wu et al teach methods of use of the glycoconjugate for immunoprotection and treatment of bacterial infections (see page 5, paragraph [0049]) and Acinetobacter baumannii in particular (see paragraph [0073]). Wu et al teach the glycoconjugate formulated for administration with an adjuvant (paragraph [0072]) and that it may be combined with other therapeutics (paragraph [0076]). The remainder of the conjugate corresponds to the instantly claimed linker, connector, carrier protein comprising a linker moiety. Inasmuch as, the structure of the linker and connector and carrier protein are not explicitly defined by language in the instant claims, the glycoconjugagte, compositions and methods (claims 13-17) of the prior art anticipate the instantly claimed products and methods. Wu et al therefore anticipates the instantly claimed invention.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Patricia Duffy whose telephone number is (571)272-0855. The examiner can normally be reached 8:00 am - 4 pm.
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/Patricia Duffy/Primary Examiner, Art Unit 1645