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 .
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.
Priority
Acknowledgment is made of the present application as a proper National Stage (371) entry of PCT Application No. PCT/US2020/067190, filed 12/28/2020, which claims benefit under 35 U.S.C. 119(e) to provisional application No. 62/955,220, filed 12/30/2019.
Status of the Claims
Claims 1, 6-11, 13-15, 17, 18, 21-23 and 27-32 are pending; claims 1, 7-11, 14, 17, 18, 21, 27 and 29 are amended; claims 30-32 are newly recited; claim 2-5, 12, 16, 19-20 and 24-26 are canceled. Claims 1, 6-11, 13-15, 17, 18, 21-23 and 27-32 are examined below.
Information Disclosure Statement
The information disclosure statement (IDS) filed 01/14/2026 is considered, initialed and is attached hereto.
Drawings
The drawings are objected to because Figures 3 and 11 appear to be provided upside down (not merely as a scanning error, but filed upside down relative to the header).
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the 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.
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.
Enablement
Claims 1, 6-11, 13-15, 17-18, 21-23 and 27-29 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification does not reasonably provide enablement for “detecting presence of one or more autoantibody associated with (APS1)”, wherein the autoantibody associated with APS1 is an anti-PLIN1 antibody (Applicant’s elected species). 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 or use the invention commensurate in scope with these claims.
The factors considered when determining if the disclosure satisfies the enablement requirement and whether any necessary experimentation is "undue" include, but are not limited to: 1) nature of the invention, 2) state of the prior art, 3) relative skill of those in the art, 4) level of predictability in the art, 5) existence of working examples, 6) breadth of claims, 7) amount of direction or guidance by the inventor, and 8) quantity of experimentation needed to make or use the invention. In re Wands, 858 F.2d 731,737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988).
Regarding the nature of the invention, the invention is directed to methods of detecting autoantibodies associated with APS1 (claims 1 and 21), and further treating subjects having APS1 based on the presence of those autoantibodies (claim 21). Applicant’s elected species of invention (see as noted previously above) is PLIN1 (autoantibodies that bind this autoantigen).
However, regarding the prior art, little is known in the prior art regarding a association between APS-1 and PLIN1 autoantibodies, or PLIN1 recognized as antigen for autoantibodies related to APS1. While autoantibodies to PLIN1 are known and detectable in those with a specific form of lipodystrophy known as AGL (acquire generalized lipodystrophy, also known as Lawrence syndrome, see Corvillo et al., Autoantibodies Against Perilipin 1 as a Cause of Acquired Generalized Lipodystrophy, Frontiers in Immunology, 9, (2018), 13 pages (IDS entered 09/27/2022)), the prior art is silent as to the correlation or association of APS-1 and these autoantibodies to PLIN1. While there appears to be many prior art recognized autoantibodies that correlate with a diagnosis of APS-1, autoantibodies to PLIN1 does not appear to be one of them.
Further, while the art does recognize that AGL and APS-1 can be diagnostically concurrent, an association between anti-PLIN1 autoantibodies and APS-1 does not appear to be known, see for example Akinci et al. Lipodystrophy Syndromes: Presentation and Treatment. [Updated 2024 Aug 21]. In: Feingold KR, Ahmed SF, Anawalt B, et al., editors. Endotext [Internet]. South Dartmouth (MA): MDText.com, Inc.; 2000-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK513130/ (provided is abstract and relevant pages 14-15). Akinci et al., specifically teach “Interestingly, one of the AGL patients with perilipin-1 antibody also had a mutation in the AIRE gene that causes autoimmune polyendocrine syndrome type 1(APS1) (88). Considering these studies, whether perilipin-1 antibodies can be a potential biomarker in AGL patients and the relationship between APS1 and lipodystrophy are still curious.” (page 14, end of first paragraph). This reference (Akinci et al.) supports that although detectable in those with APS-1, it is not readily predictable that these autoantibodies (Applicant’s elected species PLIN1) are necessarily associated with APS-1 such that they would be able to used in order to achieve a diagnosis and subsequently apply treatment.
See also Savage, Periplipin 1 Antibodies in Patients with Acquired Generalized Lipodystrophy, Diabetes, 72, (2023), p. 16-18. Savage suggests perilipin 1 antibodies manifest in those subjects who also exhibit other autoimmune disorders, Savage speculates a correlation between anti-PLIN1 autoantibodies in those with a predisposition to generating autoantibodies (see page 17, col. 1, para 1). Other than those with AGL, Savage does report “a few patients with APS1”, as those having these autoantibodies, however, importantly see Savage specifically states “Careful follow-up of APS1 cases where lipodystrophy has not been reported would be helpful, as if patients do progress to manifest lipodystrophy, this would at least be consistent with the idea that the antibodies might be involved in causing lipodystrophy rather than simply reflecting is presence”. Savage appears to be suggesting these autoantibodies are still related to/correlate with lipodystrophy, rather than APS1, which some patients with APS1 develop lipodystrophy. Savage’s suggestion for more follow up further supports the unpredictability of this autoantibody to PLIN1 as an autoantibody specifically associated with APS1, as claimed.
The level of skill in the relevant art is high, and one having ordinary skill, based on the evidence that supports unpredictability (cited above), would not readily be able to correlate/associate detection of anti-PLIN1 autoantibodies with APS-1, or a need for treatment of APS1.
Considering that little is known in the art regarding the association of anti-PLIN1 autoantibodies and a diagnosis APS-1, it is necessary to turn the originally filed specification.
Applicant’s Examples 11-14 are relevant to Applicant’s elected species of PLIN1. Example 11 (para [0160]-[0162]) describes the phage-display and immunoprecipitation protocols and validation of PLIN1 antibodies using 293T expression system, further see para [0163] describes indirect immunofluorescence performed on enteric tissue from mice, and para [0165], radioligand binding assay protocol used.
At Example 12 Applicant reports autoantibodies to PLIN1 in murine knockout of the AIRE gene, Table 6 identifies the peptides contributing to signal (peptides fragments of PLIN1, SEQ ID Nos. 42-46). Applicant, at para [0165], regarding Example 12, indicates that autoantibodies to PLIN1 were identified by screening sera from the murine knockout model, and that idiopathic antigens in previously banked sera were investigated using PhIP-Seq (a proteome wide antigen discovery method). It is acknowledged that the prior art recognizes that is has been suggested in the prior art that mutations in AIRE gene may result in autoimmune condition observed in APS1, the art suggests this diagnosis is characterized by spontaneous multi-organ failure and chronic mucocutaneous candidiasis due to immune cell destruction and dysfunction (see Nalwade et al., Aire is not essential for regulating neuroinflammatory disease in mice transgenic for human autoimmune diseases associated MHC class II genes HLA-DR2b and HLA-DR4, Cell Immunol., 331, (2018), p.38-48, at page 2, introduction paragraph 2), and that Aire-deficient mice show loss of T-cell tolerance, mimicking the phenotype of human APS1 (also paragraph 2). However, the prior art also acknowledges that flaws remain in relying on AIRE-deficient mouse models, since these models only recapitulate limited aspects of human pathology of this disease and its clinical features, and further have not been used to translate therapeutic drug candidates to the clinic (see Besnard et al., AIRE deficiency, from preclinical models to human APECED disease, Disease Models & Mechanisms, 14, (2021) (16 pages), particularly at page 1, second column, second paragraph).
Regarding the human data, see Applicant’s example 14 (para [0167]), the data presented represent one single patient (see referred to as Case report 1). This one patient, known to have APS1 (AIRE gene mutation confirmed), was tested for autoantibodies (see serum was tested, see Figure 15). Figure 15 shows increased anti-PLIN1 for this one singular patient with APS1 and lipodystrophy (the type of lipodystrophy not specified), while levels for those with just APS1 (not diagnosis for lipodystrophy) were the same as the healthy control population. Considering that those having APS1 only were the same as healthy controls, this further supports the Office’s position that autoantibodies are not considered necessarily “associated” with or particularly diagnostic for APS1.
Also, regarding those with lipodystrophy, as noted the working example in the originally filed specification does not specify which type of lipodystrophy. See Cleveland Clinic. “Overview: Lipodystrophy”. (2022), https://my.clevelandclinic.org/health/diseases/23441-lipodystrophy 16/, 18 pages. [Accessed 10/09/2025], for example. Cleveland Clinic indicates that “lipodystrophy” is a general term for a group of conditions characterized by a completed (generalized) or partial loss of fat tissue in certain areas of the body and/or abnormal fat tissue distribution (see page 1). See end of page 2-3, there are several known types of lipodystrophy recognized in the art, the types organized into two main categories (genetic and acquired), see Cleveland Clinic report the known types as familial partial lipodystrophy, acquired generalized lipodystrophy, acquired partial lipodystrophy and localized lipodystrophy.
Based on the one single human case report in Applicant’s examples, the one subject having unspecified lipodystrophy, it is also not predictable that even if the antibodies are a result of APS1 with lipodystrophy, that this would extend to all types of comorbid APS1 lipodystrophy.
Regarding the breadth of the claims, the independent claims (as noted above) are directed to detection of “autoantibody associated with …APS1”, although Applicant’s elected species for examination purposes at this time is PLIN1, the claims broadly encompass antigenic polypeptides “with at least 90% sequence identity to at least one of SEQ ID Nos. 31-46”. Seq ID Nos. 42-46 were indicated by Applicant’s attorney during an interview on 01/23/2026 to correspond to PLIN1 peptides (see as supported by Applicant’s sequence listing as well as the originally filed specification at Table 6). The claims broadly encompass detection of binding to “the antigenic polypeptides”, however, as noted in reference to Applicant’s working examples above, the working examples only support limited known polypeptide fragments (see for example, only those PLIN1 sequences as at Table 6), not any and all fragments with “at least 90% sequence identity” (see new grounds of rejection set forth in presently regarding written description, which would encompass sequences having variants such as additions, deletions and substitutions). There is no evidence to support that any and all fragments of PLIN1 are autoantigens/antigenic for anti-PLIN1 autoantibodies, and further that said autoantibodies are associated with any and all forms of lipodystrophy.
Based on the unpredictability in the art regarding what little is known about anti-PLIN1 autoantibodies and APS1 and regarding the unpredictability of the AIR deficient mouse model in clearly correlating the presence of the autoantibodies with a definitive diagnosis and subsequent treatment of APS1, the limited data provided by the single human patient case report, breadth of the claims (which is not merely limited to detecting autoantibodies to PL1N1 peptides in subjects with APS1, but rather is detecting “presence of at least one APS1 associated autoantibody” and “treating a subject” having APS1 based on said detection, and further, as amended encompasses peptides in addition to those PLIN1 peptides shown at Table 6), there is insufficient detail that would allow one of ordinary skill to make or use the claimed invention, namely which would allow one having ordinary skill in the art to detect the presence of an autoantibody associated with APS1 (specifically to indicate the autoantibodies are APS1 associated autoantibodies), and further to treat a subject having APS1 based on APS1 associated autoantibodies.
Written Description
Claims 1, 6-11, 13-15, 17, 18, 21-23 and 27-32 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.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed, and correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art. See MPEP 2163.
Claim 1 recites “contacting the biological sample with one or more antigenic polypeptides with at least 90% sequence identity to at least one of SEQ ID NOs 31-46” (claims 1 and 21), as noted Applicant’s elected species is PLIN1 (SEQ ID Nos. 42-46, see claim 30).
Regarding claims 1 and 21 (and the claims that depend from these independent claims), the claimed methods encompass a genus of polypeptides for detecting the presence of one or more autoantibodies associated with APS1. Claim 30 is broader in scope, and encompasses a genus of antibodies capable of binding antibodies in a sample. Although claim 31 recites “the one or more polypeptide comprise at least one polypeptide with a sequence of one of SEQ ID No: 42-46, this language still encompasses combinations of more than one were some species have at least 90% identity (i.e., still encompasses a genus of polypeptides).
Regarding structure of the claimed polypeptides, the language “at least 90% identity” may appear somewhat limited, however, the number of amino acid sequences comprising a deletion, substitution and/or addition of is actually enormous. For example, regarding Applicant’s elected species (SEQ ID Nos. 42-46), each of these sequences is 49 amino acid residues in length, and the claimed genus includes changes at any given position in these sequences, there is no disclosure of a minimum sequence/epitope that must be retained in order to achieve binding (i.e., to still bind and detect the presence of “autoantibodies associated with APS1”.
In addition to the above discussed structural requirements of the claimed limitations, with regarding to independent claims 1 and 21, the polypeptide must also meet certain structural requirements, namely be capable of binding and detecting one or more autoantibodies present in a sample associated with the disease APS1.
Although with the aid of a computer it may be possible to determine the amino acid sequences of the proteins that meet the structural requirements of the claim (i.e. substitutions, deletions or additions relative to SEQ ID Nos. 41-46 of PLIN1), it is not readily apparent from the claims or the specification which of these sequences that meet the claimed sequence identity are also actually capable of binding with autoantibodies present in vivo and associated with APS1.
Other than those species at Table 6, namely SEQ ID Nos. 42-46, Applicant has not disclosed any particular variants of these PLIN1 polypeptides that meet both the structural and functional requirements of the claims. Applicant has fails to indicate any particular structure, specific to all the species encompassed by the claimed genus that would correlate with the required functional ability, for example there is no indication what residues are necessary/must be retained in order to bind/detect autoantibodies associated with APS1.
As discussed above the claim scope is potentially enormous depending on how many of the sequences that meet the structural requirements also achieve the required functional ability, however, in comparison, the scope of the description is much more narrow than that which is claimed (and further, as noted in detail above regarding the enablement rejection, Example 12, the indicated peptides of Table 6, namely SEQ ID Nos. 42-46, was relevant to Aire -/- mice, Table 6 refers to the peptides contributing to the PhIP-Seq signal).
Regarding predictability in the prior art, it was known that even small changes in an antigen structure can profoundly affect antibody-antigen interactions.
For example, Harlow et al. (Harlow, E. and Lane, D., Antibodies: A Laboratory Manual (1988) Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY, pages 23-26), who teach that the loss of a single hydrogen bond can dramatically affect the ability of an antibody to recognize a cognate antigen (see especially page 26, first full paragraph).
Lederman et al. ("A single amino acid substitution in a common African allele of the CD4 molecule ablates binding of the monoclonal antibody, OKT4" Mol Immunol. 1991 Nov;28(11):1171-81) (IDS entered 01/14/2026) found that a single amino acid substitution on the antigen CD4 ablated binding of a monoclonal antibody (see title and abstract).
Similarly, Colman et al. (Research in Immunology, 1994; 145(1): 33-36 (IDS entered 01/14/2026)) teach that amino acid changes in an antigen can effectively abolish antibody antigen binding entirely (see entire document, particularly pages 33-34).
Moreover, at the time of the invention, it was recognized that analysis of a given amino acid sequence only provides rough guides as to whether the sequence will bind to antibody. See Lesniewski et al. (U.S. 6,596,476 B1) at column 5, lines 40-47, who further teach that there is no invariably predictable way to ensure whether a sequence has immunological activity short of preparing the sequence and testing it in an assay.
As such, it cannot be predicted what polypeptides having at least 90% identity to SEQ ID NOs: 42-46 (elected species) would actually be recognized by autoantibodies in patient samples.
These various references provide evidence of unpredictability due to the knowledge in the prior art regarding the nature of antibody binding.
As noted previously above, the specification provides no examples of variants of the claimed sequences wherein amino acids were modified but nonetheless achieved binding as claimed (that bound antibodies, or even further autoantibodies associated with APS1). There is no disclosure of particular regions within the claimed polypeptides responsible for binding the targeted antibodies/autoantibodies. As a result, there is no disclosed correlation between structure and function.
For all of these reasons, the claim fails to provide sufficient written description such to support that applicant was in possession of the entire genus of polypeptides as presently encompassed by the recited language.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 30-32 are rejected under 35 U.S.C. 103 as being unpatentable over Corvillo et al., Autoantibodies Against Perilipin 1 as a Cause of Acquired Generalized Lipodystrophy, Frontiers in Immunology, 9, Article 2142, (2018), 13 pages in view of Mahler et al., Advances in B-cell epitope analysis of autoantigens in connective tissue diseases, Clinical Immunology, 107, (2003), p. 65-79, as evidenced by “Perilipin-1 (PLIN1)”, Product datasheet for TP306292. Origine Technologies, Inc., (2025) (2 pages), https://www.origene.com/catalog/proteins/recombinant-proteins/tp306292-perilipin-1-plin1-nm-002666-human-recombinant-protein, [Accessed: 04/2026] (referred to herein as Origene).
Corvillo et al. teach methods of detecting one or more autoantibodies in a sample, comprising the steps of contacting sample with PLIN1, detecting the presence of binding to antibodies in the sample (see for example, ELISA described at page 4, col. 2, para 1, referring to the PLIN1 variant 1 obtained from Origene (see Origine cited above, as evidence of the sequence used in Corvillo, which is the full length protein).
Corvillo et al. fails to teach detecting binding using a smaller sequence, namely a polypeptide comprising at least one of SEQ ID NO. 42-46 (Applicant’s elected species).
However, Corvillo et al. does teach that the autoantibodies detected are autoantibodies that bind the C-terminal region of the protein (page 11, col. 1, para 1). Corvillo et al. teach further experiments are scheduled for production of fragments in order to map the epitopes recognized by anti-PLIN1 autoantibodies.
Mahler et al. teach epitope mapping of autoantigens is of interest not only for basic research but also for diagnostic and therapeutic applications, that determination of epitopes of autoantigens can facilitate development of immunoassays in which synthetic antigens may be used as substrates for autoantibody detection (see page 65, col. 1, para 1). Also, at para 1 Mahler et al. teach such diagnostically relevant structures represent ideal antigenic substrates, particularly if they can be used as short-length peptides, that peptides can be synthetized in large quantities of high purity and their small size significantly reduces the possibility of non-specific interactions with other serum components, allowing for highly sensitive specific and reproducible assays See also page 65, col. 2, para 1, Mahler teach in addition, clinically relevant peptides have been proposed as potentially useful in the treatment of autoimmune patients via the use of immobilized peptides to remove pathogenic autoantibodies.
It would have been prima facie obvious to one having ordinary skill in the art before the effective filing date of the claimed invention, to have modified Covillo’s assay in order to produce shorter C-terminal region containing peptides, for example, to have arrived at for example the peptide of SEQ ID NO. 42 by performing epitope mapping as suggested by Corvillo. In particular, one have ordinary skill in the art would have been motivated to have performed epitope mapping, as suggested by Corvillo, in an effort to produce shorter fragments because it is known in the prior art that mapping autoantigens for epitopes of interest has diagnostic and therapeutic value (Mahler). In particular, one would be motivated to modify Corvillo to determine and use shorter fragments for assay purpose for detection of the autoantibodies in order to reduce non-specific interactions, thereby producing highly sensitive specific and reproducible assays.
Even further, regarding claims 30 and 31, it would have been further prima facie obvious to have arrived at fragments (such as SEQ ID NO. 42) by epitope mapping because it was known that the autoantibodies (Corvillo) bind the C-terminal region of the full length protein (SEQ ID NO. 42 is a C-terminal region of the protein), in mapping the epitopes of PLIN1 autoantigen, one would expect to arrive at sequences including SEQ ID NO. 42 (put another way, shorter C-terminal fragments such as SEQ ID NO. 42, would have been obvious over the combined prior art). It would have been obvious to one having ordinary skill, upon determining the epitope through mapping as taught above, to have optimized fragments in order to produce peptide fragments exhibiting the least amount to non-specific interactions with other components in the sample (based on Mahler). Further because it was known (Corvillo) that the autoantibodies bind the C-terminal region, one would have a reasonable expectation of success.
Regarding claim 32, Corvillo et al. is teaching biological samples (see e.g., page 2, col. 2, para 2).
Response to Arguments
Applicant's arguments filed 01/14/2026 have been fully considered but they are not persuasive for the following reasons:
Regarding the previous rejection of claims under 35 U.S.C. 112(a), over enablement, Applicant indicates amendments to the claims in order to overcome the rejection, specifically at remarks pages 7-8 Applicant refers to the amendments to the claims to recite the SEQ ID Nos. rather than the claim referencing the tables in the specification. Applicant refers to Example 12 as supporting enablement.
See the amended grounds of rejection as set forth in detail above, the amendments to the claims do not appear to overcome the rejection to the claims.
Applicant further refers to Devoss et al. as supporting that AIRE-deficient mice were recognized as an animal model for APS1, Applicant argues this example is a working example. In response to this argument (referring to arguments at page 8), is it not disputed that Applicant’s example 12 is a working example, however, it is maintained that this example is not sufficient to support enablement for the claimed method. The example, while demonstrating that this mouse model exhibits antibodies that bind, is not sufficient to support that APS1 can be diagnosed/indicated based on the presence of autoantibodies “associated with APS1”, further that the autoantibodies are themselves specifically “associated with APS1”. The data does not clearly demonstrate that the antibodies are APS1 specific or that these autoantibodies alone are capable of achieving a positive diagnosis. See also the amended grounds of rejection detail above, specifically referring to Besnard et al., the prior art also acknowledges that flaws remain in relying on AIRE-deficient mouse models, since these models only recapitulate limited aspects of human pathology of this disease and its clinical features, and further have not been used to translate therapeutic drug candidates to the clinic.
See also new grounds of rejection set forth in response to Applicant’s amendments ot the claims.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ELLEN J MARCSISIN whose telephone number is (571)272-6001. The examiner can normally be reached M-F 8:00am-4:30pm.
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/ELLEN J MARCSISIN/Primary Examiner, Art Unit 1677
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