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 .
Election/Restrictions
Applicant’s election without traverse of Group I (i.e., claims 4, 7-9, 11-12, 14-15, 21-24, and 61-67 drawn to an HLA class II molecule) in the reply filed on May 22, 2025, is acknowledged. Additionally, Applicant’s election without traverse of Species A (i.e., a single and specific HLA class II molecule as comprising a DP beta chain of SEQ ID NO: 3 where the amino acid at position 141 is Met and the amino acid at position 112 is Trp, and a DP alpha chain of SEQ ID NO: 6, where the HLA class II molecule is a DP1 allele, and where the DP beta chain is bound to a membrane of a cell and comprises an extracellular domain of a full length DP beta chain); and Species B (i.e., a single and specific complex of Species A as a single and specific HLA class II molecule and SEQ ID NO: 56 as a single and specific peptide) in the reply filed on May 22, 2025, is acknowledged.
Please note that in light of Applicant’s search, Species B is hereby withdrawn.
Additionally, please note that Species A is hereby withdrawn as the claimed invention is free of the prior art as further articulated below.
Status of Claims
Claims 1-61 were originally filed on January 31, 2022.
The amendment received on December 23, 2022, canceled claims 1-3, 5, 10, 13, 16-18, 20, 25-41, 43-44, 47-50, and 53-60; and amended claims 6-9, 11-12, 14-15, 19, 21, 23-24, 45-46, 51-52, and 61. The amendment received on May 22, 2025, canceled claims 42, 46, and 51-52; amended claim 4; and added new claims 62-67. The amendment received on 12/11/25, canceled claims 7-9, 11-12, 14, 62 and 67; and amended claims 4, 15, 61, 63, and 65-66.
Claims 4, 15, 19, 21-24, 61, and 63-66 are currently pending and are under consideration.
Priority
The present application claims status as a 371 (National Stage) of PCT/IB2020/057175 filed July 29, 2020, and claims priority under 119(e) to U.S. Provisional Application Nos. 62/880,496 filed on July 30, 2019, and 63/029,111 filed May 22, 2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on December 11, 2025, is being considered by the examiner.
Sequence Interpretation
For claim 4, please note that the Examiner is interpreting the scope as open-ended requiring 100% identity to SEQ ID NO: 3 with any N- and/or C-terminal additions. It is noted that SEQ ID NO: 3 has a Trp residue at position 112 and a Met residue at position 141.
For claim 15, please note that the Examiner is interpreting the scope as open-ended requiring 100% identity to SEQ ID NO: 4 with any N- and/or C-terminal additions.
For claims 21 and 63, please note that the Examiner is interpreting the scope as open-ended requiring at least about 80% identity to SEQ ID NO: 6 or 8 with any N- and/or C-terminal additions. “About” is defined as encompassing +/- 10% (See instant, [0066]). As such, the scope of claim 21 encompasses at least 70% identity to SEQ ID NO: 6 or 8. It is noted that SEQ ID NO: 6 contains 192 amino acids thereby encompassing up to 57 amino acid modifications such as deletions and/or substitutions. It is noted that SEQ ID NO: 8 contains 269 amino acids thereby encompassing up to 80 amino acid modifications such as deletions and/or substitutions.
For claim 22, please note that the Examiner is interpreting the scope as open-ended requiring 100% identity to SEQ ID NO: 6 or 8 with any N- and/or C-terminal additions.
For claim 61, please note that the Examiner is interpreting the scope as open-ended requiring two components; namely, an HLA class II molecule of claim 4, and one or more peptides comprising an amino acid sequence that requires 100% identity to one or more of SEQ ID NOs: 32-237 with any N- and/or C-terminal additions.
For claim 64, please note that the Examiner is interpreting the scope as open-ended requiring 100% identity to SEQ ID NO: 6 or 8 with any N- and/or C-terminal additions.
Response to Arguments
Applicant’s arguments, see Response, filed 12/11/25, with respect to claim objections have been fully considered and are persuasive. The objections of claims 4, 7-9, 11-12, 14-15, 19, 21-24, 61-65, and 67 have been withdrawn.
Applicant’s arguments, see Response, filed 12/11/25, with respect to the objection to the specification have been fully considered and are persuasive. The objection of the specification has been withdrawn.
Applicant’s arguments, see Response, filed 12/11/25, with respect to the 112(a), written description, rejection have been fully considered and are persuasive. The rejection of claims 4, 7-9, 11-12, 14, 19, 21-24, and 61-65 as failing to comply with the written description requirement has been withdrawn.
Applicant’s arguments, see Response, filed 12/11/25, with respect to the 112(b) rejection have been fully considered and are persuasive. The rejection of claims 4, 7-9, 11-12, 14, 19, 21-24, and 61-65 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 has been withdrawn.
Applicant’s arguments, see Response, filed 12/11/25, with respect to the 112(b) rejection have been fully considered and are persuasive. The rejection of claims 4, 7-9, 11-12, 14, 19, 21-24, and 61-65 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 has been withdrawn.
Applicant’s arguments, see Response, filed 12/11/25, with respect to the 112(d) rejection have been fully considered and are persuasive. The rejection of claim 15 as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends has been withdrawn.
Applicant’s arguments, see Response, filed 12/11/25, with respect to the 101 rejection have been fully considered and are persuasive. The rejection of claims 4, 7-9, 11-12, 19, and 23-24 as being directed to a product of nature without significantly more has been withdrawn.
Applicant’s arguments, see Response, filed 12/11/25, with respect to the 102(a)(1) rejection have been fully considered and are persuasive. The rejection of claims 4, 7, and 23-24 as being anticipated by GenBank Accession number XP_023576849 (HLA class II histocompatibility antigen, DP beta 1 chain-like [Octodon degus], 24 January 2018) has been withdrawn.
Applicant’s arguments, see Response, filed 12/11/25, with respect to the 103(a) rejection have been fully considered and are persuasive. The rejection of claims 4, 7-9, 11-12, and 23-24 as being unpatentable over Anderson et al. US Publication No. 2018/0244759 A1 published on August 30, 2018 in view of UniProt Accession No. P04440, DPB1_Human, (first available 1987), and UniProt Accession No. P04440, DPB1_Human, variant viewer (P04440 first available 1987, variant viewer for V170M last updated 2015), alone or as evidenced by UniProt Accession No. A0A0D6K9C3, MHC class II antigen, DPB1 (2015) has been withdrawn.
Applicant’s arguments, see Response, filed 12/11/25, with respect to the 103(a) rejection have been fully considered and are persuasive. The rejection of claims 4, 19, and 21 as being unpatentable over Anderson et al. US Publication No. 2018/0244759 A1 published on August 30, 2018 in view of UniProt Accession No. P04440, DPB1_Human, (first available 1987), UniProt Accession No. P04440, DPB1_Human, variant viewer (P04440 first available 1987, variant viewer for V170M last updated 2015), alone or as evidenced by UniProt Accession No. A0A0D6K9C3, MHC class II antigen, DPB1 (2015), as applied to claim 4 above, and further in view of UniProt Accession No. P20036, DPA1_Human, (first available 1991), and Cruz-Tapias et al., Major histocompatibility complex: Antigen processing and presentation. In: Anaya JM, Shoenfeld Y, Rojas-Villarraga A, et al., editors. Autoimmunity: From Bench to Bedside [Internet]. Bogota (Colombia): El Rosario University Press; 2013 Jul 18. Chapter 10. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459467/ has been withdrawn.
Applicant’s arguments, see Response, filed 12/11/25, with respect to the obviousness-type double patenting rejection have been fully considered and are persuasive. The rejection of Claims 4, 7-9, 11-12, 14, 19, 21-22, 24, and 61-64 as being unpatentable over claims 1, 7, 13, 57, 59, 63, 79, 84, 85, and 94 of copending Application No. 17/631,824 (Hirano et al. US Publication No. 2022/0281949 A1) in view of UniProt Accession No. P20036, DPA1_Human, (first available 1991) has been withdrawn.
Applicant’s arguments, see Response, filed 12/11/25, with respect to the obviousness-type double patenting rejection have been fully considered and are persuasive. The rejection of claims 4, 7-9, 11-12, 14, 19, 21-22, 24, and 61-64 as being unpatentable over claims of copending Application No. 17/631,821 (Hirano et al. US Publication No. 2022/0275051 A1) in view of UniProt Accession No. P20036, DPA1_Human, (first available 1991) has been withdrawn.
New Objections
Claim Objections
Applicant is advised that should claim 23 be found allowable, claim 65 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
New Rejections Not Necessitated by Amendment
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.
Claims 21 and 63 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Dependent claims 21 and 63 include a “DP alpha chain that comprises an amino acid sequence having at least about 80% identity to SEQ ID NOs: 6 or 8”. As discussed in the “Sequence Interpretation” section supra, “about 80%” encompasses +/- 10%, i.e., “about” is defined in the specification as encompassing +/- 10% (See instant [0066]) thereby encompassing a sequence identity of at least 70% to one of SEQ ID NOs: 6 or 8. As such, at least 70% of SEQ ID NO: 6 encompasses up to 57 amino acid modifications, and at least 70% of SEQ ID NO: 8 encompasses up to 80 amino acid modifications. Amino acid modifications include a vast array of structural modifications such as conservative substitutions, non-conservative substitutions, deletions, and/or insertions without a core structure or sequence. Therefore, the DP alpha chain amino acid sequence of claims 21 and 63 encompass a vast array of structural modifications without a core structure or sequence. In addition to the broad structure encompassed by the claimed invention, the instant specification defines a typical MHC Class II molecule as comprising two protein chains: an alpha chain and a beta chain (See instant, [0071]). A HLA class II molecule binds with an antigenic peptide in a peptide-binding groove of the molecule that is found between the alpha-1 and beta-1 domains where such binding results in the presentation of the antigenic peptide extracellularly to CD4+ cells (See instant, [0075]). Both the alpha- and beta-chains fold into two separate domains; the alpha-1 and alpha-2 for the alpha polypeptide, and the beta-1 and beta-2 for the beta polypeptide (See instant, [0075]). The open-ended peptide-binding groove which holds the presented antigen is found between the alpha-1 and beta-1 domains (See instant, [0075]). As such, the alpha chain including the DP alpha chain is essential for proper binding of a HLA class II molecule to an antigenic peptide, presentation of the antigenic peptide once bound to the molecule, and binding of the molecule to a CD4+ T cell. Thus, in light of the specification, the claimed HLA class II molecule comprising a DP alpha chain amino acid sequence must exhibit the function of binding to an antigenic peptide, presenting the antigenic peptide extracellularly, and binding to a CD4+ T cell.
The written description requirement may be met by provided a representative number of species of the genus and/or in light of the state of the art. With regard to the state of the art, Diaz et al. teaches that molecules encoded within the class II region of the MHC are polymorphic, non-covalently associated αβ heterodimers whose function is to bind peptide antigens derived from extracellular proteins and display them on the cell surface for interaction with CD4+ T lymphocytes (See Diaz et al., Intl. Immunol. 15:565-576 (2003) at pg. 565, col. 1, last paragraph to col. 2, 1st paragraph) (See also: Lauterbach et al., Molec. Immunol. 59:19-29 (2014) at pg. 19, col. 1, last paragraph). Characterization of MHC class II peptide binding and T cell recognition, at the molecular level, is essential to understand a central event of the immune response that could have important applications in clinical practice (See Diaz, pg. 565, col. 2, last paragraph to pg. 566, col. 1, 1st paragraph). DP is one of three isotypes of human MHC class II molecules (See Diaz, pg. 566, col. 1, 2nd paragraph) (See also: Lauterbach, pg. 19, col. 1, last paragraph). Diaz et al. examined polymorphisms in the DP beta chain 1 (See Diaz, pg. 566, col. 2, 2nd paragraph; pg. 573, col. 1, 2nd paragraph) whereas Lauterbach et al. also examined polymorphisms in the DP alpha chain on CD4+ T cell alloreactivity (See Lauterbach, pg. 20, col. 1, last paragraph to col. 2, 1st paragraph). The HLA-DP alpha chain shows limited polymorphism compared to the beta chain, but still the DPA1 alleles encode 19 different cell surface proteins (See Lauterbach, pg. 20, col. 1, 3rd paragraph). Lauterbach et al. examined amino acid polymorphism encoded by exon 2 of DPA1 alleles at positions 11, 18, 28, 31, 50, 72-73, and 83 (See Lauterbach, Table 4). Lauterbach et al. found that CD4+ T cell allorecognition of HLA-DP is significantly affected by DPA1 polymorphism (See Lauterbach, pg. 24, last paragraph). In particular, Lauterbach et al. found significant differences in allorecognition for a specific T cell effectors when specific DPB1 alleles are combined with different DPA1 alleles (See Lauterbach, pg. 25, col. 2, 1st paragraph). Further, Lauterbach et al. found that DPA1 residues 11, 31, 50, and 72-73 as potentially relevant for T cell allorecognition (See Lauterbach, pg. 26, col. 2, 1st paragraph; Figure 5). Plus, Lauterbach et al. identified a polymorphic residue at position 11 located inside the peptide binding groove as a position that could influence peptide binding (See Lauterbach, pg. 26, col. 2, 1st paragraph; Figure 5). Similarly, the model structure proposes the amino acid residues at position 31 inside the groove and at position 50 outside the groove as potentially able to affect peptide binding and TCR recognition (See Lauterbach, pg. 26, col. 2, 4th paragraph). Lauterbach et al. then concludes that all targets tested with deviating DPA1 background but identical DPB1 alleles resulted in a lower recognition by the effector T cells thereby affecting immunogenicity (See Lauterbach, pg. 26, col. 2, last paragraph; pg. 27, 3rd paragraph). Thus, although Lauterbach teaches several residues critical to a MHC class II molecule to function properly, Lauterbach demonstrates that even one substitution within a specific full length DP chain allele amino acid sequence can have a serious impact on the functionality of a MHC class II molecule. Therefore, the claims are directed to MHC class II molecules comprising varied DP alpha chain amino acid sequences with a certain function but no correlated structure associated with that function. Without such structure, the specification does not convey possession of the breadth of the claimed genus.
Alternatively, the written description requirement may be met by providing a representative number of species of the genus. In this, the specification teaches a limited number of species within the claimed genus. More specifically, the specification teaches that the alpha chain is a wild-type alpha chain or a naturally occurring allele (See instant, [0022], [0131]-[0132]). Moreover, the specification uses the wild-type DPA1*01:03 (DPα) gene (i.e., instant SEQ ID NO: 6) expressed with a mutant DPB1*04:01 (DP4β) gene with four substitutions, i.e., L112W, V114M, V141M, and M158I (See instant, Example 2, [0042]; [0202]). Although this mutant MHC class II molecule exhibited enhanced binding to soluble CD4+ T cells compared to the wild-type DP4 molecules the L112W and V141M substitutions were critical for enhanced binding to CD4 (See instant, Example 2, [0202]; Figure 1G), the enhanced binding is the result of the DPB1 modifications. However, the specification does not identify any critical amino acid positions in the DP alpha chain necessary for the MHC class II molecule to function properly. Nor does the specification teach any DP alpha chain with specific substitutions at specific positions. As such, the specification does not constitute a representative number of species given the breadth of the claimed genus discussed supra. Thus, the specification is not sufficient for the skilled artisan to envisage which DP alpha chain amino acid sequences that are at least 80% identical to SEQ ID NOs: 6 or 8 will preserve function.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, what is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of polypeptides which preserve the required function, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. Therefore, claims 21 and 63 do not meet the written description requirement.
New Rejections Necessitated by Amendment
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 23 and 65 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claims 23 and 65 are directed to where the HLA class II molecule is a DP1, DP2, DP3, DP4, DP5, DP6, DP8, or DP9 allele. However, claims 23 and 65 are dependent upon claim 4, which now requires the HLA class II molecule to comprise 100% identity to SEQ ID NO: 3. As depicted in Table 1 in the instant specification, SEQ ID NO: 3 represents DPB1*04:01 (See instant, Table 1). As such, the HLA class II molecule of claim 4 is already limited to a DP4 allele, and cannot be one of the other recited alleles. Thus, the scope of claims 23 and 65 broaden the scope of claim 4. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim 24 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 24 is directed to where the DP beta chain comprises an extracellular domain of a full length DP beta chain (i.e., option (c)). However, claim 24 is dependent upon claim 4, which now requires the HLA class II molecule to comprise 100% identity to SEQ ID NO: 3. As depicted in Table 1 in the instant specification, SEQ ID NO: 3 already contains a full length beta chain. As such, the scope of claim 24 encompasses an embodiment that does not further limit the scope of claim 4. It is noted that options (a)-(b) and (d)-(g) properly further limit. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Maintained/Modified Rejections in light of Applicants’ Amendments
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 4, 15, 19, 21-24, 61, and 63-66 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 6-7, 10, 14-16, 24, 27-28, 48, 53-55, 80, 83, 89, 93, and 98 of copending Application No. 17/631,818 (Hirano et al. US Publication No. 2022/0291215 A1). Although the claims at issue are not identical, they are not patentably distinct from each other because ‘818 claims:
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(See ‘818 claims 1-2, 10, 14-16, 83, and 89). As such, the ‘818 claimed method constitutes a method of using the instant HLA class II molecule and instant complex where the HLA class II molecule comprises a DP1 beta chain comprising a Trp substitution at a position corresponding to L112 and a Met substitution at a position corresponding to V141 of instant SEQ ID NO: 1 thereby constituting 100% identity to instant SEQ ID NO: 3 and a DP alpha 1 chain having 100% identity to instant SEQ ID NO: 6 (i.e., HLA-DPA*01 allele comprises instant SEQ ID NO: 6). Thus, the ‘818 claimed invention anticipates instant claims 4, 15, 19, 21-23, 63-65. Moreover, since ‘818 uses the instant HLA class II molecule, the ‘818 HLA class II molecule would inherently exhibit an increased affinity for a CD4 protein compared to a HLA class II molecule comprising a DP beta chain comprising instant SEQ ID NO: 1 as recited in instant claim 66. Plus, ‘818 claiming that the MHC class II molecule is expressed on the surface of an APC constitutes where the DP beta chain is bound to a membrane of a cell as recited in instant claim 24. Although ‘818 does not specify the peptide amino acid sequence complexed with the HLA class II molecule, an ordinary skilled artisan would be motivated with a reasonable expectation of success to utilize instant SEQ ID NO: 228 (i.e., human CLIP amino acid sequence) since it is well-known that the CLIP invariant fragment is complexed with the MHC class II molecule before the molecule binds to an antigenic peptide. Therefore, the ‘818 claimed invention is not patentably distinct from the instantly claimed invention.
Applicants’ Arguments
Applicant’s contend that since instant claim 51 was restricted as being independent and distinct from the product claims elected, the obviousness-type double patenting rejection over the 818 co-pending application would similarly be patentably distinct (See Applicant’s Response received on 12/11/25, pg. 13).
Response to Arguments
Applicant's arguments filed 12/11/25 have been fully considered but they are not persuasive for the following reasons.
In response to Applicant’s argument, i.e., since instant claim 51 was restricted as being independent and distinct from the product claims elected, the obviousness-type double patenting rejection over the ‘818 co-pending application would similarly be patentably distinct, it is found unpersuasive. The consideration for restriction purposes is distinct from the consideration of obviousness-type double patenting purposes. As stated in the Restriction mailed on 11/22/24, the consideration for restriction was based on whether the shared technical feature lacks unity of invention in light of the prior art. Thus, patentable distinction and independence are not a criteria for election/restriction purposes under 35 USC §121 and 35 USC § 372. Rather, unity of invention pursuant to 37 C.F.R. §1.475 governs.
Regarding consideration for obviousness-type double patenting purposes, MPEP 804 states that nonstatutory double patenting includes rejections based on anticipation, a one-way determination of "obviousness," or a two-way determination of "obviousness." It is important to note that the "obviousness" analysis for "obviousness-type" double-patenting is "similar to, but not necessarily the same as, that undertaken under 35 U.S.C. 103." In re Braat, 937 F.2d 589, 592-93, 19 USPQ2d 1289, 1292 (Fed. Cir. 1991) (citing In re Longi, 759 F.2d 887, 892 n.4, 225 USPQ 645, 648 n.4 (Fed. Cir. 1985)); Geneva Pharmaceuticals, 349 F.3d 1373, 1378 n.1, 68 USPQ2d 1865, 1869 n.1 (Fed. Cir. 2003). MPEP 804(II)(B) states that the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate. To decide the question above, the examiner should first construe the claim(s) in the application under examination and the claim(s) in the reference application or patent to determine what are the differences. Then the examiner should determine whether those differences render the claims patentably distinct using an anticipation analysis and/or an obviousness analysis. See Pfizer, Inc. v. Teva Pharms. USA, Inc., 518 F.3d 1353, 1363, 86 USPQ2d 1001, 1008 (Fed. Cir. 2008). In the instant case, the question to ask is whether the ‘818 claimed invention anticipates or renders obvious the instant invention. The Examiner maintains the answer is yes. As discussed in the rejection supra, the ‘818 claimed method uses the instant HLA class II molecule. Thus, the ‘818 claimed invention anticipates instant claims 4, 15, 19, 21-23, and 63-66, and renders obvious instant claim 61 by utilizing the one-way test for obviousness.
Accordingly, the rejection of claims 4, 15, 19, 21-23, and 63-66 is maintained as Applicants’ arguments are found unpersuasive.
Examiner Comment
Notwithstanding the 112(b) and obviousness-type double patenting rejections, it is noted that the claimed invention is free of the prior art as there is no teaching or suggestion for a DP beta chain comprising 100% identity with any N- and/or C-terminal additions to SEQ ID NO: 3. The closest prior art is Anderson et al. US Publication No. 2018/0244759 A1 published on August 30, 2018 (cited in the Action mailed on 8/11/25). Anderson et al. teaches a method of generating an immune response including enhancing the generation of antibodies by using a protein’s “peptidogenic potential” via altering the conformational dynamics of a starting protein while maintaining that protein’s 3D conformation (See Anderson, [0032]). A “peptidogenic protein” refers to a mutated protein that has been modified in its amino acid sequence to alter its conformational dynamics as compared to the starting protein sequence while maintaining a similar conformation to the starting protein (See Anderson, [0042]). An exemplary peptidogenic protein includes SEQ ID NO: 185, which is human HLA class II histocompatibility antigen, DP beta 1 chain as a specific protein target (See Anderson, Table 5, SEQ ID NO: 185). Anderson’s SEQ ID NO: 185 encompasses up to 30 amino acids that can be substituted (See Anderson, Table 5, SEQ ID NO: 185). One of the exemplified sites of mutation to generate peptidogenic proteins is L141 (See Anderson, Table 5, SEQ ID NO: 185). It is noted that L141 corresponds to instant position L112 when the signal peptide is included in the amino acid sequence. Anderson et al. teaches that L141 can be substituted with Ala, Val, Gly or Ile (See Anderson, Table 5, SEQ ID NO: 185). However, Anderson does not teach or suggest where instant L112 is substituted to L112W or where instant V141 is substituted to V141M. Thus, the claimed invention is free of the prior art.
Conclusion
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/THEA D' AMBROSIO/Primary Examiner, Art Unit 1654