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 .
DETAILED ACTION
1. Applicant’s amendment and response filed 2/17/2026 is acknowledged and has been entered.
2. Applicant is reminded of Applicant's election without traverse of Group I and species of:
soluble composition, HLA-DQ2, a Jun/Fos zipper at the C-termini of the alpha chain or the portion thereof and the beta chain or the portion thereof and a linker at the N-terminus of the beta chain or the portion thereof connected to the MHC ligand peptide, a peptide linker comprises the first cysteine and the second cysteine is a substitution for a natural non-cysteine amino acid residue in the MHC II alpha chain or the portion thereof (i.e., R101C), an MHC II alpha chain sequence lacking a cysteine present in the corresponding wild type MHC II molecule consists of amino acid residues 24-216 of SEQ ID NO: 54, wherein the elimination of an unpaired cysteine (i.e., C70A) is the substituent amino acid residue. (Note that SEQ ID NO: 49 corresponds to the HLA-DQ alpha 1 can (UniProt Acc. No. P01909-1, while SEQ ID NO: 54 corresponds to Applicant’s elected species of HLA-DQ2 alpha chain having R101C, C70A substituent amino acid residues in SEQ ID NO: 49).
in Applicant’s amendment and response filed 10/17/25.
Claims 1-3, 5, 7-13, 16, 34, 41, 45, 52 and 53 read upon the elected species.
Applicant’s amendment filed 2/17/26 has necessitated that search and examination be extended to previously withdrawn claim 4 (species comprising TM and cytoplasmic domains) and the species of membrane-anchored composition recited in instant claim 5 in part.
Claims 1-5, 7-13, 16, 34, 41, 44, 45, 52 and 53 are presently being examined as they read upon the elected species and the species enunciated above. Claim 1 is an independent claim.
3. Applicant’s amendment filed 2/17/26 has overcome the prior rejection of claims 1-3, 5, 7-13, 16, 34, 36, 38, 39, 41, 43-45, 48-50 and 52-56 under 35 USC 112(a) or 35 USC 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement.
Applicant has amended the claims to recite that the molecule is an HLA-DQ2 molecule and the location of the second cysteine in the MHC class II alpha chain when aligned with SEQ ID NO: 49 (the first is comprised in the peptide linker), as well as to recite the lack of a naturally present cysteine in the said alpha chain when aligned with SEQ ID NO: 49. Although the HLA-DQ2 alpha chain sequences are polymorphic, they are known in the art. In addition Applicant has canceled claims 36, 38, 43, 48-50 and 54-56.
4. Applicant’s amendment and response has overcome the prior rejection of record of claims 11 and 45 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.
Applicant has amended claim 11 to delete the recitation of “an MHC-Jun linker” and “an MHC-Fos linker” and has stated on the record with regard to claim 45 and the recitation of a pan-DR-binding epitope (PADRE) that the epitope refers to a mouse MHC II binding sequence as described in Alexander et al. (J. Immunol., 2000, 164(3)” 1625-1633, IDS reference) and points to paragraph [00127] of the specification. Therefore, the recitation of a pan-DR-binding epitope is not a broad recitation followed by a narrower recitation (i.e., there are other pan-DR binding/promiscuous epitopes known in the art besides PADRE).
5. 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.
6. Applicant’s amendment filed 2/17/26 has overcome the prior rejection of record of claims 1-3, 5, 7, 13, 16, 34, 36, 44, 45, 48-50 under 35 U.S.C. 102(a)(i) as being anticipated by WO2019/051126 A1 (IDS reference).
The art reference does not teach the new claim limitations that comprise an HLA-DQ2 molecule comprising an alpha chain with the recited cysteine substituent amino acid residue at a position corresponding to position 101 in the sequence set forth in SEQ ID NO: 49 when the MHC class II alpha chain is optimally aligned with SEQ ID NO: 49. In addition, Applicant has canceled claims 36 and 48-50.
7. Applicant’s amendment filed 2/17/26 has overcome the prior rejection of record of claims 1-3, 5, 7-10, 13, 16, 34, 36, 44, 45 and 48-50 under 35 U.S.C. 102(a)(i) as being anticipated by WO2018/087597 A1 (IDS reference).
The art reference does not teach the new claim limitations that comprise an HLA-DQ2 molecule comprising an alpha chain with the recited cysteine substituent amino acid residue at a position corresponding to position 101 in the sequence set forth in SEQ ID NO: 49 when the MHC class II alpha chain is optimally aligned with SEQ ID NO: 49. In addition, Applicant has canceled claims 36 and 48-50.
8. Applicant’s amendment filed 2/17/26 has overcome the prior rejection of record of claims 1-3, 5, 7-13, 16, 34, 36, 44, 45, 48-50, 52 and 53 under 35 U.S.C. 103 as being unpatentable over WO2019/051126 A1 (IDS reference) in view of WO 2010/037397 A1 (IDS reference) and Ruiz et al. (Mol. Immunol., 2007, 44: 2205-2212) because the references do not teach the presently recited claim limitations, as discussed above for the primary art reference in this prior rejection of record.
9. Applicant’s amendment filed 2/17/26 has overcome the prior rejection of record of claims 1-3, 5, 7-10, 12, 13, 16, 34, 36, 44, 45, 48-50, 52 and 53 under 35 U.S.C. 103 as being unpatentable over WO2018/087597 A1 in view of WO 2010/037397 A1 (IDS reference) and Ruiz et al. (Mol. Immunol., 2007, 44: 2205-2212) because the references do not teach the presently recited claim limitations, as discussed above for the primary art reference in this prior rejection of record.
10. 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.
11. Claims 4 and 5 (in part) 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 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.
Applicant’s amendment filed 2/17/2026 has necessitated the following new ground of rejection.
“To be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without ‘undue experimentation.’” Genentech, Inc. v. Novo Nordisk, A/S, 108F.3d 1361, 1365, 42 USPQ2d 1001, 1004 (Fed. Cir. 1997) (quoting In re Wright, 999F2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)). In In re Wands 8 USPQ2d 1400 (CAFC 1988), a number of factors are set forth which a court may consider in determining whether a disclosure would require undue experimentation. These factors were set forth as follows: (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. All the factors need not be reviewed when determining whether a disclosure is enabling. Amgen, Inc. v. Chugai Pharm. Co., Ltd., 927F2.d 1200, 1213, 18 USPQ2d 1016, 1027 (Fed. Cir. 1991) (noting that the Wands factors “are illustrative, not mandatory. What is relevant depends upon the facts.”).
The specification does not disclose how to make and/or use the instant invention recited in claim 4: a composition comprising the MHC class II molecule recited in claim 2 and ultimately in instant base claim 1, wherein the MHC class II alpha chain comprises the alpha 1 domain, an alpha 2 domain, a TM (transmembrane) domain, and a cytoplasmic domain, and the MHC class II beta chain comprises the beta 1 domain, a beta 2 domain, a TM domain, and a cytoplasmic domain. The specification does not disclose how to make and/or use the instant invention recited in claim 5 in part (i.e., “the composition of claim 1, “wherein the composition is membrane-anchored” and wherein the MHC class II molecule is missing critical component(s) such as TM and cytoplasmic domains for cell membrane anchoring and signaling in the absence of a definition for “cell membrane anchored” in the specification).
The specification has not enabled the breadth of the claimed invention because: (1) claim 4 encompasses a polypeptide composition comprising a hydrophobic TM domain and also a cytoplasmic domain that is not anchored in a cell or a cell membrane, wherein it is unpredictable that the composition can be made and/or used; and (2) claim 5 in part encompasses a polypeptide that must be membrane anchored such as in the membrane of a cell but is missing critical portions required for such anchoring, wherein it is unpredictable that the composition can be made and/or used.
As is evidenced below, artificial membranes were known in the art for anchoring MHC class II molecules lacking a hydrophobic TM domain and a cytoplasmic domain; however, the MHC class II molecules were anchored for example, via a tag rather than through a TM domain. Alternatively, the art also recognizes that polypeptides that are anchored in the membrane of an intact cell require at least a TM region for the anchoring and a cytoplasmic domain in the case of MHC class II molecules in order to signal. The specification does not disclose a limiting definition for “membrane-anchored”, but does discuss species of MHC class II molecules that are naturally membrane anchored [in an intact cell] (e.g., [0069], [0082]). The specification does not disclose artificial membrane anchoring of MHC class II molecules.
The specification discloses that the term “MHC” encompasses “HLA” or human MHC molecules [0052], but does not limit the term to only human MHC molecules. The scope of the claim therefore encompasses over 10,000 different human MHC class II molecules and those MHC class II molecules that are present in other non-human vertebrates. Evidentiary reference HLA Nomenclature (2023, 2 pages) teaches that there are over 10,000 different human MHC class II molecules alone. The state of the art evidences that although the overall structure and antigen-presenting functions of human and non-human MHC class II molecules are conserved, potential differences in amino acid composition, especially in hydrophobic regions, can affect stability and folding during recombinant production.
As pertains to unpredictability in making the recited MHC class II molecule, evidentiary reference Hu et al (Protein Science, 2007, 16: 2153-2165) teaches that transmembrane domains have a highly hydrophobic amino acid composition and because of the near absence of water in the transmembrane environment, the whole balance of molecular interactions that stabilizes protein structure is altered (paragraph spanning pages 2153-2154, first paragraph of the Discussion section). Hu et al teach that proteins and their domains are significantly influenced by their environment, and the expression, purification, and sample preparation for these constructs can be challenging (first paragraph on page 2153). (See entire reference.) It is therefore unpredictable that such a molecule can be made; even if it could, it is equally unpredictable that it can be used since it comprises a TM and a cytoplasmic domain, with the TM domain being highly hydrophobic.
Evidentiary reference Ma et al. (Micr. Res. Techn., 2011, 74: 1174-1185) teaches that a peptide/MHC class II molecule (one having extracellular domains of MHC class II alpha and beta chains with no TM domain and no cytoplasmic domain) was made with a fused C-terminal 6xHis tag and attached to an artificial membrane via reaction of the 6xHis tag with a DOGS-NTA moiety on the artificial membrane (see entire reference). However, this construct taught by Ma et al. did not comprise TM and cytoplasmic domains (unlike the polypeptide recited in the instant claim).
The specification does not disclose any working examples of making isolated MHC class II molecules comprising the extracellular domain (i.e., the alpha 1 and 2 and beta 1 and 2 domains), the TM, and a cytoplasmic domain as a polypeptide construct, nor of membrane-anchored MHC class II molecules that lack a TM domain and a cytoplasmic domain.
There is insufficient guidance in the specification as to how to make and/or use the instant invention. Undue experimentation would be required of one skilled in the art to practice the instant invention. See In re Wands 8 USPQ2d 1400 (CAFC 1988).
Applicant may potentially obviate this rejection in part as pertains to claim 4 by amending the claim 4 to recite a cell comprising the MHC class II molecule as an independent claim incorporating the limitations of its base claims.
12. Claims 1-3, 7-13, 16, 34, 41, 44, 45, 52 and 53 are allowed. Claims 4 and 5 are rejected. Claims 57-61 are withdrawn.
13. 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.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIANNE DIBRINO whose telephone number is (571)272-0842. The examiner can normally be reached on M, T, Th, F.
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/Marianne DiBrino/
Marianne DiBrino, Ph.D.
Patent Examiner
Group 1640
Technology Center 1600
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
Prosecution Insights