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 .
The response filed 6-10-2026 has been entered into the record. Claims 1-9 and 17-20 are pending.
Priority
Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Sequences in the Figures
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-8 in the reply filed on 6-10-2026 is acknowledged.
Claims 9 and 17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 6-10-2026.
Information Disclosure Statement
The information disclosure statements have been considered. Initialed copies are enclosed.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
New corrected drawings in compliance with 37 CFR 1.121(d) are required in this application because Figures 1a-1c are illegible. The corrected drawings are required in reply to the Office action to avoid abandonment of the application. The requirement for corrected drawings will not be held in abeyance.
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.
Claims 1-8 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
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 a composition or a vaccine composition comprising H. contorus recombinant antigens (i) enolase (EN);(ii) arginine kinase (AK); and(iii) ornithine decarboxylase (ODC), or antigenic fragments thereof and further comprising one or more of recombinant H. contortus antigens selected from the group consisting of:(iv) seryl tRNA synthetase (SRS-2);(v) macrophage migration inhibitory factor 2 (MIF-2);(vi) fatty acid synthetase (FASN-1);(vii) NAD (P)H-dependent oxidoreductase (F36A2-3);(viii) glutamyl tRNA synthetase (ERS-2);(ix) aspartyl tRNA synthetase (DRS-1);(x) transcriptional co-activator (CBP-1);;(xi) vacuolar ATPase (VHA-12); and(xii) serum-glucocorticoid-inducible kinase (SGK-1) or antigenic fragments thereof. The antigens are described functionally as enzymes and structurally by SEQ ID NOS:1-12 in Table 2 of the specification. The specification contemplates homologs and sequence variants (see specification page 13, first paragraph; page 13, 70-99% sequence identity at the last paragraph). and antigenic fragments (page 12, last paragraph).
Knowledge of the prior art
The specification teaches that the H. contortus recombinant antigens that recombinant vaccines against parasitic nematodes have met with limited success and to date there are no commercial recombinant vaccine available for any nematode parasites (specification page 1, last paragraph). The dictionary definition of vaccine is "A prophylactic or therapeutic material containing antigens derived from one or more pathogenic organisms which, on administration to man or animal, will stimulate active immunity and protect against infection with these or related organism (i.e. produce protective immunity)." (The Dictionary of Immunology, Herbert et al eds, Academic Press, 1995). Vaccines by definition trigger an immunoprotective response in the host vaccinated and mere antigenic response is insufficient. It is well recognized in the vaccine art, that it is unclear whether an antigen(s) derived from a pathogen will elicit protective immunity. Ellis, R.W. (Chapter 29 of "VACCINES" [Plotkin, S.A. et al. (eds) published by W. B. Saunders company (Philadelphia) in 1988, especially page 571, 2nd full paragraph] exemplifies this problem in the recitation that "The key to the problem (of vaccine development) is the identification of that protein component of a virus or microbial pathogen that itself can elicit the production of protective antibodies.... and thus protect the host against attack by the pathogen".
The specification fails to teach variants or fragments of SEQ ID NOS:1-12 that in fact confer protection from infection, reduce worm burden, reduced fecal egg count, increase in expulsion of larvae or adult nematode worms, as is requisite of a vaccine composition in this field of endeavor. None of the art recognized homologs listed in Table 1, have been demonstrated to have vaccine properties with the heterologous species H. contortus nematode or against the homologous nematode. Variants have protective activity have not been described. Similarly, the antigenic fragments of the claimed recombinant antigens that provide for a protective immune response are unknown and cannot be derived from mere homologous/percent identical features/areas, without more. The art is replete with evidence that the ability to produce an antibody (immunogenicity) is insufficient to correlate with protection from infection. See for example Feng et al (Infection and Immunity, 64(1):363-365, 1996) that teaches that P55, is an immunogenic but nonprotective 55-kilodalton Borrelia burdorferi protein in murine lyme disease. Chandrashekar et al (US Patent 6,248,329) teach that “Although many investigators have tried to develop vaccines based on specific antigens, it is well understood that the ability of an antigen to simulated antibody productions does not necessarily correlate with the ability of the antigen to stimulate an immune response capable of protecting an animal from infection…” (column 1, lines 35-41). The specification does not teach any homologs or variants or fragments that provide protection as described. The ability to raise an immune response does not necessarily correlate with a protective immune response for reasons set forth supra. The specification fails to disclose a single protective antigenic fragment for any of SEQ ID NOS:1-12, homologs and percent identical variants. The courts have held that it is the specification, not the knowledge of one skilled in the art, that must supply the novel aspects of an invention in order to constitute adequate enablement. (Genentech Inc. v. Novo Nordisk A/S Ltd., 42 USPQ2d 1001). Moreover, the specification must have been enabling at the time the invention was made and developments after the time of filing are of no consequence to what one skilled in the art would have believed at the time of filing (In re Wright, 27 USPQ2d 1510).
The immunological equivalent variants/vaccines related by identity or enzyme homologs and antigenic fragments are not enabled because it is well established in the art that the retention of the specificity of antibodies following one or more amino acid substitutions in a polypeptide is a factor that has been shown to be unpredictable in the art. For instance, McGuinness et al. (Mol. Microbiol. 7: 505-514, Feb 1993) taught that “[a] single amino acid change within an epitope, or an amino acid deletion outside an epitope, were both associated with loss of subtype specificity resulting from a change in the predicted conformation at the apex of the loop structure” in case of a meningococcal polypeptide (see abstract). Similarly, McGuinness et al. (Lancet 337: 514-517, March 1991) taught that a point mutation generating a single amino acid change in a P1.16-specific epitope in the VR2 region of the porA gene of a strain of Neisseria meningitidis of subtype P1.7,16 resulted in “striking changes in the structural and immunological properties of the class 1 protein” of this isolate (see abstract and page 514). Additionally, Houghten et al. (New Approaches to Immunization, Vaccines86, Cold Spring Harbor Laboratory, p. 21-25, 1986) taught the criticality of individual amino acid residues and their positions in peptide antigen-antibody interactions. Houghten et al. state (see page 24): "One could expect point mutations in the protein antigen to cause varying degrees of loss of protection, depending on the relative importance of the binding interaction of the altered residue. A protein having multiple antigenic sites, multiple point mutations, or accumulated point mutations at key residues could create a new antigen that is precipitously or progressively unrecognizable by any of the antibodies in the polyclonal pool." The specification does not teach variations or antigenic fragments of SEQ ID NOS:1-12 that function as vaccines for H. contortus or any other nematode.
Guidance provided by inventor/working examples
The specification teaches that vaccine compositions comprising at least 75 ug of each antigen of SEQ ID NOS:1-12 formulated in an adjuvant QuilA in a Solgel formulation three different formulations 3AgV, 7AgV and 11AgV provided for decreased worm burden and reduced fecal egg count. No variants, homologs or antigenic fragments were produced and shown to have protection as set forth in the specification.
Level or degree of predictability
The level of unpredictability is high, given that no recombinant antigens or fragments thereof have been of limited success and no commercial recombinant vaccines exist for comparison. However, 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.
Quantity of experimentation
The quantity of experimentation is enormous, and the art is highly unpredictable. 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 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 as written are prima facie non-enabled.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-7 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter.
The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because the claimed invention is directed to a natural product without significantly more. The claims recite a combination of H. contortus enzymes/antigens or antigenic fragments thereof with a veterinary acceptable carrier or diluent and adjuvant. This judicial exception is not integrated into a practical application because the antigens are not integrated into a practical application. The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because each of the enzymes/antigens have no structural differences from those found in nature. Even though the claims recite “recombinant” polypeptides or antigen fragments thereof they appear to be the same as the naturally occurring polypeptides and they are not markedly different. Eligibility requires more than the hand of man, to be eligible the claimed product must be both non-naturally occurring and markedly different from naturally occurring products (see page 1, third full paragraph). In the instant case, the claimed enzymes/antigens or antigenic polypeptide fragments does not markedly structurally differ from that found in nature whose sequences comprise the claimed fragments or enzymes/antigens. The removal of the isolated fragment from the intact naturally occurring polypeptide does not provide a marked structural difference of the fragment from that which is naturally occurring. The isolation of the polypeptide fragment does not confer a marked difference on the polypeptide per se. As such, the claimed product is not patent eligible see analogous rationale in Association for Molecular Pathology v Myriad Genetics, Inc., 569 U.S. 576, 589-91, 106 USPQ2d 1972, 1978-79 (2013)) set forth for isolated nucleic acids. The claimed compositions comprising the isolated polypeptides/enzymes/antigens and antigenic fragments do not meet the criteria as it merely combines the isolated polypeptide fragment with naturally occurring carriers/diluents and adjuvants such as CpG, cytokines and lipopolysaccharides. The term “recombinant” also does not confer a structural difference with respect to the naturally occurring polypeptide/enzyme/antigen as the means of producing the polypeptide does not appear to confer a marked structural difference from the naturally occurring structure/sequence. The claimed compositions comprising protein/enzymes are not markedly different from the naturally occurring counterparts found in the intact nematode H. contortus or distinguish from the nematode per se. With respect to the elements recited in addition to the judicial exception of a naturally occurring polypeptide or antigenic fragment thereof, the following is found: (1) it recited at a high level of generality such that substantially all practical applications of the judicial exception is covered and/or (2) it recites an element that is well understood, purely conventional or routine in the field of biotechnology. The claimed composition is also merely a combination of natural products or antigenic fragments with naturally occurring carriers and diluents and (2) an generic adjuvant. Funk Brothers Seed Co. v. Kalo Inoculant Co., 33 U.S. 127 (1948).
For the foregoing reason, the compositions are not patentable under 35 USC 101.
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 1-5 and 7 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Molina et al (Veterinary Parasitology, 188:53-59, 2012; of record).
The claims are drawn to compositions or vaccines comprising various H. contortus recombinant enzymes in combination with veterinary acceptable diluents, carriers or adjuvants. Molina teaches adult H. contortus worms homogenized in phosphate buffered saline (see page 54, column 2, second full paragraph). The H.contortus antigens are inherently present in the composition and phosphate buffered saline is a veterinary acceptable carrier and diluent. The term recombinant does not structurally distinguish between the naturally produced and the recombinantly produced antigens. Furthermore, the term “vaccine” in the preamble of the claims represents the intended use of the composition and does not distinguish the structure of the claimed composition from that inherently in the prior art.
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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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Patricia Duffy/Primary Examiner, Art Unit 1645
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