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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 October 23, 2025 and Supplemental Response dated November 7, 2025 have been entered. By way of these submissions, Applicant has amended claim 1 and introduced new claims 21-23.
Claims 1-3, 9, 16-17, and 21-23 are pending in the application. Claim 16 remains withdrawn from consideration, pursuant to the Restriction Requirement mailed May 3, 2021.
Claims 1-3, 9, 17, and 21-23 are therefore under examination before the Office.
The rejections of record can be found in the previous Office action, dated August 7, 2025.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on September 25, 2025 was filed after the mailing date of the first Office action on the merits on November 19, 2021. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-3, 9 and 17 were previously rejected under 35 U.S.C. 103 as being unpatentable over Essen-Moller (WO2015187087A2) in view of Pociot (Lancet. 2016 Jun 4;387(10035):2331-2339).
Applicant argues that it would not be obvious in view of the teaching of Pociot that some individuals with type 1 diabetes have both a homozygous HLA-DR3-DQ2 haplotype and GAD autoantibodies, to then treat those individuals with GAD-alum, and that Figure 3A of Pociot shows that at early ages, it is the insulin autoantibodies (IAA), not GADA, that are more prevalent in heterozygous individuals. Applicant argues that there are well-known failures of using GAD-alum as a therapy, and one of ordinary skill would not be motivated to pursue this therapy.
Applicant's arguments in view of the amendments to the claims have not addressed this issue fully. In the interest of compacting prosecution, the above rejection is withdrawn, and the following new grounds of rejection is issued:
Claims 1-3, 9, 17, and 21-23 rejected under 35 U.S.C. 103 as being unpatentable over Lernmark (Trends Immunol. 2005 Nov;26(11):608-12, cited previously) in view of Krischer (Diabetologia. 2015 May;58(5):980-7, cited in IDS), Alshiekh (Textbook of Diabetes, 5th Edition), and Morales (Immunotherapy. 2011 Mar;3(3):323-32, cited previously).
Lernmark teaches treating patients with latent autoimmune diabetes (LADA) with GAD65 formulated in alum (page 610, right column, third paragraph and Box 1), which is pertinent to claims 1 and 3.
Lernmark further teaches that patients with LADA have autoantibodies against GAD65 (page 610, left column, second paragraph), which is pertinent to claim 2.
Lernmark further teaches subcutaneous injection of GAD65 in alum for treatment of LADA (page 610, right column, third paragraph), which is pertinent to claim 9.
Lernmark further teaches that it is useful to assess (i.e. identify) subjects for diabetes treatments based on HLA haplotype to predict the possible effects of autoantigens, such as alum-formulated GAD65, as GAD65 autoantibodies are associated with a DR3 haplotype (page 610, right column, third and fourth paragraphs).
However, Lernmark does not teach identifying the individual as having an at least one copy of an HLA DR3-DQ2 haplotype.
Krischer teaches that GAD autoantibodies are associated with the HLA-DR3 haplotype (page 986, left column, first paragraph: "Our observations that the appearance of IAA only tends to be associated with the HLA-DR4 haplotype while GADA only was associated with the HLA-DR3 haplotype is of considerable interest. ... The strong association between HLA and the seroconversion to a specific islet autoantibody therefore underscores prior observations that the association between HLA and type 1 diabetes at the time of clinical diagnosis are secondary to a primary association between HLA and an autoimmune response to either IAA only or GADA only.")
Krischer further teaches that GAD autoantibodies are present in HLA-DR3/3 children (page 981, left column, second paragraph), which is pertinent to claim 17.
Alshiekh teaches that GAD autoantibodies as a first islet autoantibody is associated with HLA-DR3-DQ2 (page 145, right column, second paragraph, page 147, left column, second paragraph, and Figure 10.2).
Morales teaches that GAD-alum modulates the general memory immune responses to GAD65, thereby promoting the preservation of beta-cells in patients with LADA (page 325, left column, first paragraph and Executive summary). Since beta cell functionality is preserved, the patient must have some beta cell activity prior to treatment, which is pertinent to claim 22.
Morales also teaches that GAD-alum moderates levels of C-peptide both fasting and after a meal (page 326, second paragraph). Since C-peptide activity is moderated, the patient must have some C-peptide activity prior to treatment, which is pertinent to claim 23.
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Lernmark, Krischer, Alshiekh, and Morales to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since Lernmark, Krischer, Alshiekh, and Morales are all concerned with treatment of type 1 diabetes. Starting with the treatment method of Lernmark, which states that GAD65 formulated in alum is useful to treat type 1 diabetes, as well as suggesting that HLA haplotype may be relevant to inform treatment, the skilled artisan could apply the teachings of Krischer and Alshiekh to connect the HLA DR3-DQ2 haplotype to the presence of GAD autoantibodies. The mechanism of action is taught by Morales, which teaches that GAD-alum causes proliferation of GAD65-specific regulatory T cells, which downregulate antigen-specific killer T cells, preventing their attack on pancreatic beta cells. Each component of the combination would perform its known, usual function, and the combination would yield nothing more than predictable results.
In response to Applicant's arguments, Essen-Moller and Pociot are no longer relied upon in this rejection. Lernmark and Morales both teach the use of GAD-alum for the treatment of LADA. Applicant's specification at page 1 also clearly concedes that GAD-alum can preserve beta-cell function in patients with recent-onset type 1 diabetes.
Figure 10-2(a) and (d) of Alshiekh clearly indicate that patients with the HLA-DR3-DQ2 haplotype are much more likely to express GAD autoantibodies. The mechanism of using GAD65 antigen in patients with GAD autoantibodies is also taught by Morales. The application of a known solution to a known problem is prima facie obvious.
Conclusion
No claim is allowed.
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/PETER JOHANSEN/Examiner, Art Unit 1644