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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 1/21/2026 has been entered.
DETAILED ACTION
Claims 18, 20, 23, 25-28, and 30 are pending and under examination on their merits. Claims 1-17, 19, 21-22, 24, and 29 are cancelled.
Response to Arguments
Applicant’s arguments filed 1/21/2026 are moot because the previous rejections under 35 U.S.C. §101 and 35 U.S.C. §103 are withdrawn.
Claim Objections
Claims 18 and 20 are objected to because of the following informalities: antigen, antibody, and anti- are unnecessarily italicized.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 18, 20, 23, 25-28, and 30 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.
Claim 18 recites both an anti-Malassezia antibody and an anti-Malassezia antigen antibody. The term “antigen antibody” is not an art-recognized term and there is no special definition provided within the specification. It is unclear whether the anti- Malassezia antigen antibody differs in scope from the anti-Malassezia antibody and whether there is a structural difference between these two claim limitations.
Claims 20, 23, 25-28, and 30 are rejected for depending from a rejected base claim and not rectifying the source of indefiniteness discussed above.
Claim 20 is indefinite because the claim recites “comprises” (open transitional phrase) in each of the wherein clauses. Claim 20 depends from claim 18, which recites a method “consisting of” (closed transitional phrase). Therefore, it is unclear whether the claimed method includes additional unrecited steps.
Claim 27 recites an amino acid substitution, S12N, without a reference SEQ ID NO. Although the claim recites rs4077515, this is an NIH reference SNP report, which is subject to change. See rs4077515 (2024, website), “History” section, which shows multiple updates.
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 18, 20, 23, 25-28, and 30 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. This is a new matte rejection.
Claim 18 recites measuring an elevated level of anti-Malassezia antigen antibody. Claim 20 requires that detecting the presence of anti-Malassezia antigen antibody comprises contacting an antibody capable of specifically binding to anti-Malassezia antigen antibody to form a binding complex.
The term “anti-Malassezia antigen antibody” is not disclosed in the specification and the specification does not define the term. There is no art-recognized definition for an “antigen antibody.” Therefore, this term introduces new matter. Claims 23, 25-28, and 30 depend from claim 18, which recites the new matter, so they are rejected here as well.
Claims 18, 20, 23, 25-28, and 30 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.
Claim 18 is drawn to a method of measuring an elevated level of Malassezia, Malassezia antigen, anti-Malassezia antibody, anti-Malassezia antigen antibody or Malassezia lipase. Claim 20 further limits the step of measuring an elevated level of Malassezia, Malassezia antigen, anti-Malassezia antibody, anti-Malassezia antigen antibody or Malassezia lipase. Claim 20 recites a genus of antibodies capable of specifically binding to a Malassezia antigen, antibodies capable of specifically binding to an anti-Malassezia antibody or an anti-Malassezia antigen antibody, and antibodies capable of specifically binding to Malassezia lipase. Claim 20 requires an antibody that is described solely by the antigen to which it binds – Malassezia, a Malassezia antigen, an anti-Malassezia antibody, or a Malassezia lipase. In one embodiment, the claims are generic to any antigen of Malassezia, which encompasses all bacterial components, including intracellular and secreted proteins. The claims are not limited to any particular species of Malassezia.
The person of ordinary skill in the art would not have recognized that the inventors had possession of the claimed genus of antibodies capable of specifically binding to a Malassezia antigen, antibodies capable of specifically binding to an anti-Malassezia antibody or an anti-Malassezia antigen antibody, or antibodies capable of specifically binding to Malassezia lipase.
The specification discloses in [0213] that the antibody comprises a monoclonal antibody, a chimeric antibody, a CDR-grafted antibody, a humanized antibody, a Fab, a Fab', a F(ab')2, a Fv, a disulfide linked Fv, a scFv, a single domain antibody, a diabody, a multispecific antibody, a dual specific antibody, an anti-idiotypic antibody, a bispecific antibody, an IgG antibody, an IgM antibody and/or an IgE antibody. However, the specification does not disclose the antibody structure with claimed antigen-binding functions. Fig. 25A of the specification illustrates higher levels of anti-M. restricta IgG and anti-M. restricta IgA in patients with high ASCA IgA and ASCA IgG. The specification also discloses that ASCA+ sera reveals the presence of anti-Malassezia Lip1-specific IgA when the patients are homozygous for the CARD9S12N (Fig. 25D). Similar results are found for anti-Lip1 IgG and Lip1 from M. globosa ([0335]). In other words, the specification detects the presence of antibodies using the recombinant lipase antigen but never discloses the structure of the antibodies that actually bind to the antigen. The specification never discloses the structure of any species of antibody capable of specifically binding to Malassezia antigen, any species of antibody capable of specifically binding to an anti-Malassezia antibody or an anti-Malassezia antigen antibody, or species of antibody capable of specifically binding to Malassezia lipase.
The state of the art indicates that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences that maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites. MacCallum et al. (Psychological methods 1.2 (1996): 130) teaches that although no single residue is in contact with the antigen in all structures, the CDR3 of the heavy and light chain dominate (MacCallum pg. 733, paragraph bridging columns). MacCallum teaches that contacts are more common at CDR residues which are located centrally within the combining site and non-contacting residues within the CDRs are important in defining "canonical" conformations (MacCallum Abstract).
De Pascalis et al. (the Journal of Immunology 169.6 (2002): 3076-3084) engineers a less immunogenic humanized monoclonal antibody by grafting CDRs onto the frameworks of the variable light and variable heavy regions of human monoclonal antibodies (Abstract). Although abbreviated CDR residues are used in the constructs, some residues in all 6 CDRs are used for the constructs (see De Pascalis page 3080, left column, paragraph 2).
Casset et al. (Biochemical and biophysical research communications 307.1 (2003): 198-205.) demonstrates the fact that not just one CDR is essential for antigen binding or maintaining the conformation of the antigen binding site: Casset constructs a peptide mimetic of an anti-CD4 monoclonal antibody binding site by rational design (Casset Abstract). Casset’s peptide mimetic is formed by 27 residues from 5 CDRs (Casset Abstract). Casset also teaches that although CDR H3 is at the center of most, if not all, antigen interactions, clearly other CDRs play an important role in the recognition process (Casset page 199, left column, paragraph 2) Casset uses all CDRs except L2 and additionally uses a framework residue located just before the H3 (Casset see page 202, left column, paragraph 1).
Vajdos et al. (Journal of molecular biology 320.2 (2002): 415-428) teaches that antigen binding is primarily mediated by the CDRs and that the more highly conserved framework segments that connect the CDRs are mainly involved in supporting the CDR loop conformations (page 416, left column, bottom paragraph). However, in some cases framework residues also contact the antigen (page 416, left column, bottom paragraph).
Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function. Rudikoff et al. (Proceedings of the National Academy of Sciences 79.6 (1982): 1979-1983. 1982) teaches that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function (Abstract).
The above references demonstrate that an antibody must comprise all 6 CDRs in order to maintain the antigen binding specificity and affinity which is characteristic of the immunoglobulin.
The instant claims fail to meet the requirements for disclosure because the antibody is described solely by the antigen to which it binds (a Malassezia antigen, an anti-Malassezia antibody, or a Malassezia lipase). The specification does not disclose all 6 CDRs for any antibody; therefore, it does not teach the structure associated with the claimed function for the antibody.
There is an absence of structurally-characterized species of the claimed genus of antibodies against Malassezia antigens in the prior art as well. Hiragun et al. (Allergology International 63.1 (2014): 83-93; cited in the Non-Final Action mailed on 4/9/2024) teaches detecting antibodies against MGL_1304 (secreted by Malassezia globosa; see Abstract Background): serum from 20 patients with atopic dermatitis (AD) is pooled (page 84, right column, Establishment of ELISA systems for measurement of MGL_1304-specific immunoglobins, first paragraph), 96 well plates are coated with purified MGL_1304 (page 84, right column, Establishment of ELISA systems for measurement of MGL_1304-specific immunoglobins, second paragraph), and the wells are incubated with patient sera (bottom line of right column on page 84 through first paragraph on left column page 85). However, Hiragun does not teach the structure of the anti-MGL_1304 antibodies.
Based on the above analysis, the person of ordinary skill in the art would not have recognized that the inventors had possession of the claimed invention at the time the application was filed.
Applicant may consider amending claim 18 as follows in order to obviate the rejections of claim 18 under 35 U.S.C. 112(b) and under 35 U.S.C. 112(a) written description and new matter.
18. A method of measuring an elevated level of Malassezia or Malassezia lipase in a human subject suspected of having inflammatory bowel disease (IBD) or having IBD, consisting of:
obtaining a biological sample from the subject;
assaying the biological samples to detect Malassezia or Malassezia lipase in the biological sample;
measuring the elevated level of Malassezia or Malassezia lipase as compared to each respective control level;
diagnosing the human subject as having IBD; and
administering an anti-fungal therapy to the human subject to treat IBD, wherein the antifungal therapy is selected from the group consisting of posaconazole, triazole, imidazole, clotrimazole, ketoconazole, itraconazole, terconazole, oxiconazole, miconazole, econazole, tioconazole, voriconazole, fluconazole, isavuconazole, itraconazole, pramiconazole, ravuconazole, amphotericin B, nystatin, natamycin, caspofungin, anidulafungin, micafungin, naftifine, terbinafine and combinations thereof.
Conclusion
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/LOUISE W HUMPHREY/Supervisory Patent Examiner, Art Unit 1657
/CANDICE LEE SWIFT/Examiner, Art Unit 1657