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 3/30/26 is acknowledged and has been entered.
2. Applicant is reminded of Applicant's election without traverse of the species of SEQ ID NO: 3 in Applicant’s amendment and response filed 6/24/25.
Claims 1, 7, 80, 83, 89, 93, 98 and newly added claims 101-106 read upon the elected species. Upon consideration of the prior art, search and examination is presently being extended to include the species of SEQ ID NO: 13 and 21, SEQ ID NO: 1 with 112W/141M, SEQ ID NO: 11 with 114W/143M/110Q/116V/118H/146Q, SEQ ID NO: 19 with 114W/143M/139T/157I and further variant with any of 139T, 146Q, 163M or 164T.
Claims 1, 7, 80, 83, 89, 93, 98 and 101-106 are presently being examined. Claims 1, 102 and 104 are independent claims.
3. Applicant is reminded that the disclosure is objected to because of the following informality: The last page of the specification still contains the abstract.
Appropriate correction is required.
Applicant has stated that the abstract has been provided on a separate page (see Applicant’s response filed 3/30/26 on page 10). However, the abstract is on the last numbered page of the specification and the page is labeled as the specification.
4. Applicant’s amendment filed 3/30/26 has overcome the prior rejection of record of claims 1, 2, 6, 7, 10, 14-16, 80, 83, 89, 93 and 98 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.
Applicant has canceled claims 2, 6, 7, 10, 14-16 and has amended instant base claim 1 to recite specific HLA-DP alpha chain and a specific HLA-DP beta chain having 112W and 141M substituent amino acid residues therein.
5. Applicant’s amendment filed 3/30/26 has overcome the prior rejection of record of claims 6 and 7 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 canceled claim 6 and has amended both base claim 1 and instant dependent claim 7.
6. 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.
7. Claims 89, 98 and 103 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.
This is a new ground of rejection necessitated by Applicant’s amendment filed 3/30/26.
a) Claim 89 at part “(iv)” (and also therefore at part “(v)”) is indefinite in the recitation of “the MHC class II molecule has an affinity for CD4 that is at least about 2-fold higher than the binding affinity of a naturally occurring MHC class II molecule to CD4” because it is not clear what is meant, i.e., the HLA-DP molecule that is recited in the method of instant claim 89 has an HLA-DP alpha chain and an HLA-DP beta chain having two substituent amino acid residues, those of 112W and 141M; an HLA-DP4 L112W/V141M has a KD of binding to CD4 of 8.9 mM +/- 1.1 (see the specification at [0322]). The specification also discloses that prior studies have estimated that the KD value between CD4 and HLA class II is greater than 2 mM (ibid). The specification does not disclose a limiting definition of the term “about” (i.e., “The term “about” is used herein to mean approximately, roughly, around, or in the regions of. When the term “about” is used in conjunction with a numerical range, it modifies that range by extending the boundaries above and below the numerical values set forth. In general, the term “about” is used herein to modify a numerical value above and below the stated value by a variance of 10 percent, up or down (higher or lower).”). A KD of 8.9 mM is more than a 10% variance from 2 mM. In the latter case, the limitation at part (iv)” of claim 89 lacks antecedent basis in the base claim for HLA-DP with the recited variant amino acid residues in the beta chain. There is no evidence of record that a different HLA-DP beta chain with the substitutions 112W/141M (such as the ones recited in dependent claim 7) would bind CD4 at the recited affinity.
b) Claim 98 is indefinite in the recitation of “wherein the MHC class II molecule binds CD4 with a KD of less than about 100 uM” because it is not clear what is meant for the same reasons as are stated above at part “a)”.
c) Claim 103 recites “the method of claim 102, wherein the beta chain comprises the amino acid sequence set forth in SEQ ID NO: 13”. This limitation lacks antecedent basis in instant base claim 102 because claim 102 recites at part “(vi)” that there is a glutamine at a position corresponding to amino acid residue 146 of SEQ ID NO: 11, whereas SEQ ID NO: 13 has an asparagine at that said position.
d) Claim 106 recites “the method of claim 104, wherein the beta chain comprises the amino acid sequence set forth in SEQ ID NO: 21. This limitation lacks antecedent basis in instant base claim 104 because claim 104 recites at part “(iii)” “a threonine at a position corresponding to amino acid residue 139 of SEQ ID NO: 19”, whereas SEQ ID NO: 21 has a lysine at position 139.
8. 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.
9. This is a new ground of rejection necessitated by Applicant’s amendment filed 3/30/26.
Claim 105 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 1 recites “The method of claim 104, wherein the beta chain further comprises…” and lists the substituent amino acids and their positions as alternatives at parts “(v)”-(“viii)”. In the instant case, “a threonine at a position corresponding to amino acid residue 139 of SEQ ID NO: 19” recited at part “(v)” of dependent claim 105 is a duplication of that recited at part “(iii)” in base claim 104.
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.
10. Applicant’s amendment filed 3/30/26 has overcome the prior rejection of record of claims 6, 7, 10 and 14-16 on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984).
Applicant has canceled claims 6, 7, 10 and 14-16.
11. 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.
12. Applicant’s amendment filed 3/30/26 has overcome the prior rejection of record of claims 1, 80, 83, 89, 93 and 98 under 35 U.S.C. 103 as being unpatentable over Novak et. al. (JCI, 1999, 104(12): R63-R67) in view of GenBank CQR91450.1 (7/21/2017), and Castelli et. al. (J. Immunol. 2002, 169(12): 6928-6934), as evidenced by Emboss needle I20251219-162402-0853-9904998 (2025).
Applicant has amended the claims to recite a 112W/141M beta chain HLA-DP variant that is not taught by the art references.
13. 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.
14. This is a new ground of rejection necessitated by Applicant’s amendment filed 3/30/26. Applicant has amended the claims and has added new claim 101.
Court rulings have been quite clear that ONLY DIVISIONAL applications are entitled to the shield from double patenting under 35 USC 121. Indeed, in AMGEN INC v. HOFFMANN LA ROCHE LTD GMBH LA (Nos. 2009-1020, 2009-1096) the court discusses this issue at length and states:
Turning to the legislative history, the court observed that a House Report also referred specifically to “divisional application[s].” Id. Notably absent from the legislative history, in the court's view, was a suggestion “that the safe-harbor provision was, or needed to be, directed at anything but divisional applications.” Id. at 1361. From there, the court “conclude^] that the protection afforded by section 121 to applications (or patents issued therefrom) filed as a result of a restriction requirement is limited to divisional applications.” Id. at 1362. Accordingly, the court decided that the § 121 safe harbor did not apply to the patent before it, which issued from a continuation-in-part application. Id.
We are persuaded by the reasoning in Pfizer that the § 121 safe harbor provision does not protect continuation applications or patents descending from only continuation applications. The statute on its face applies only to divisional applications, and a continuation application, like a continuation-in-part application, is not a divisional application.
Given that Applicant chose to file the 17/631,820 case as a separate unrelated application, not as a DIV of the instant application, the instant rejection has been set forth.
Claims 1, 7, 80, 83, 89, 93, 98 and 101 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4, 15, 19, 21-24, 61 and 63-66 of copending Application No. 17/631,820 in view of Novak et al. (JCI, 1999, 104(12):R63-R67, of record) and Castelli et al. (J. Immunol. 2002, 169(12): 6928-6934, of record).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The claims of 17/631,820 are drawn to an HLA-DP molecule comprising a beta chain having the sequence of SEQ ID NO: 3 (identical to instantly recited SEQ ID NO: 3, Applicant’s elected species) and wherein the HLA-DP molecule comprises a peptide, wherein the molecule has an increased affinity for a CD4 protein as compared to a reference HLA class II molecule. The first sequence depicted below is instantly recited SEQ ID NO: 3, whereas the second sequence is SEQ ID NO: 3 from 17/631,820. They are 100% identical.
Aligned_sequences: 2
# 1: EMBOSS_001
# 2: EMBOSS_001
# Matrix: EBLOSUM62
# Gap_penalty: 10.0
# Extend_penalty: 0.5
#
# Length: 196
# Identity: 196/196 (100.0%)
# Similarity: 196/196 (100.0%)
# Gaps: 0/196 ( 0.0%)
# Score: 1063.0
EMBOSS_001 1 RATPENYLFQGRQECYAFNGTQRFLERYIYNREEFARFDSDVGEFRAVTE 50
EMBOSS_001 1 RATPENYLFQGRQECYAFNGTQRFLERYIYNREEFARFDSDVGEFRAVTE 50
EMBOSS_001 51 LGRPAAEYWNSQKDILEEKRAVPDRMCRHNYELGGPMTLQRRVQPRVNVS
EMBOSS_001 51 LGRPAAEYWNSQKDILEEKRAVPDRMCRHNYELGGPMTLQRRVQPRVNVS
EMBOSS_001 101 PSKKGPLQHHNWLVCHVTDFYPGSIQVRWFLNGQEETAGVMSTNLIRNGD
EMBOSS_001 101 PSKKGPLQHHNWLVCHVTDFYPGSIQVRWFLNGQEETAGVMSTNLIRNGD
EMBOSS_001 151 WTFQILVMLEMTPQQGDVYTCQVEHTSLDSPVTVEWKAQSDSARSK 196
EMBOSS_001 151 WTFQILVMLEMTPQQGDVYTCQVEHTSLDSPVTVEWKAQSDSARSK 196
The claims of 17/631,820 do not teach wherein the complex is used in a method of identifying an MHC class II specific TCR comprising contacting a T cell with a complex comprising the MHC class II molecule and a peptide.
Novak et al. teach that soluble tetramerized class II HLA molecule loaded with an antigenic peptide and fluorescently labeled can be used to directly identify antigen-specific T cells from peripheral blood by contacting the HLA class II tetramers with the T cells and analyzing them by flow cytometry (i.e., selecting the T cells comprising a TCR, or “identifying an MHC class II specific TCR” on a T cell (e.g., abstract, Figure 3 and legend). Novak et. al. teach that such a direct method advantageously avoids the need for limiting dilution analysis and permits simultaneous phenotypic analysis of the antigen-specific T cells using flow cytometry, and providing a means for understanding the immune response against infectious agents and in autoimmune disease (last paragraph of reference). See entire reference.
Castelli et al. teach that it was within the purview of one of ordinary skill in the art to discover and make recombinant versions of peptides that bind to HLA-DP molecules (see entire reference).
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have used the HLA-DP molecule as a tetramer of an HLA-DP/peptide complex having an HLA-DP alpha chain and an HLA-DP beta chain comprising the sequence of SEQ ID NO: 3 and a peptide bound thereto, the beta chain having the recited increased affinity of binding to CD4, to identify T cells having a cognate antigen-specific TCR as per the teaching of Novak et. al.
One of ordinary skill in the art would have been motivated to do this, and with a reasonable expectation of success in doing so, in order to identify cognate T cells for a different HLA class II molecule, and particularly in view of the recitation of increased affinity binding to CD4 [on T cells].
Instant claim 83 is included in this rejection because an exemplary HLA class II binding peptide taught by Novak et al. is 12 amino acid residues in length, while it was known in the art that HLA class II to be from 9 to about 18 amino acid residues in length (see for example Castelli et. al.) and the definition of “about” in the instant specification allows for 10% variance (i.e., 9 to 11 amino acid residues) while the recitation of “at least” preceding “about” in the claim establishes a lower limit of 9 to 10 amino acid residues. Instant claim 3 is included in this rejection because flow cytometry is used to “select” the T cell bound by the MHC class II molecule. Although the claims of 17/631,820 do not recite that the HLA-DP molecule binds to CD4 with the affinity recited in dependent claim 98 or in claim 89 at part “(iv)”, the instant specification discloses that the SEQ ID NO: 3 variant (i.e., the HLA-DP4L112W/V141M variant) that is identical to that recited in the claims of 17/631,820 bound to CD4 with a KD of 8.9 uM +/- 1.1 which represents an at least 200-fold improvement in the binding affinity (see the specification at [0322].
Instant dependent claim 7 is also included in this rejection because evidentiary reference PIR Acc. No. A02229, 2004 teaches that instantly recited SEQ ID NO: 3 is identical to residues 30-225 of HLA-DP4 beta chain except for the 112W and 141M substituent amino acid residues, indicating that the MHC class II molecule comprises a DP4 allele (recited in instant dependent claim 7), reproduced below:
PIR/GenCore
HLHUPB
MHC class II histocompatibility antigen HLA-DP beta 1 chain (allele DPB4.1) precursor - human
C;Species: Homo sapiens (man)
C;Date: 17-Mar-1987 #sequence_revision 17-Mar-1987 #text_change 09-Jul-2004
C;Accession: A02229; B29313; A29973; A30536; I68752; I54472; S04656
R;Kelly, A.; Trowsdale, J.
Nucleic Acids Res. 13, 1607-1621, 1985
A;Title: Complete nucleotide sequence of a functional HLA-DPbeta gene and the region between the DPbeta1 and DPalpha1 genes: comparison of the 5' ends of HLA class II genes.
A;Reference number: A02229; MUID:85215568; PMID:2987832
A;Accession: A02229
A;Molecule type: DNA
A;Residues: 1-258 <KEL>
A;Cross-references: UNIPROT:P04440; UNIPARC:UPI000004494C; GB:X02228; NID:g32194; PIDN:CAA26147.1; PID:g296648
A;Note: the authors translated the codon TAC for residue 36 as Thr
R;Gustafsson, K.; Widmark, E.; Jonsson, A.K.; Servenius, B.; Sachs, D.H.; Larhammar, D.; Rask, L.; Peterson, P.A.
J. Biol. Chem. 262, 8778-8786, 1987
A;Title: Class II genes of the human major histocompatibility complex. Evolution of the DP region as deduced from nucleotide sequences of the four genes.
A;Reference number: A92652; MUID:87250502; PMID:3036829
A;Accession: B29313
A;Molecule type: DNA
A;Residues: 1-258 <GUS>
A;Cross-references: UNIPARC:UPI000004494C; GB:M23908; GB:J02738; GB:M15447; NID:g188417
R;Compagnone-Post, P.; Turco, E.; Robinson, C.; Trucco, M.
Genomics 2, 8-13, 1988
A;Title: The beta-chains of DP4 molecules from different haplotypes are encoded by the same gene.
A;Reference number: A29973; MUID:88256155; PMID:2838415
A;Accession: A29973
A;Molecule type: mRNA
A;Residues: 1-258 <COM>
A;Cross-references: UNIPARC:UPI000004494C; GB:J03041; NID:g184192; PIDN:AAA35993.1; PID:g306858
A;Experimental source: allele DP4
A;Note: the authors translated the codon GAG for residue 86 as Asp
R;Bugawan, T.L.; Horn, G.T.; Long, C.M.; Mickelson, E.; Hansen, J.A.; Ferrara, G.B.; Angelini, G.; Erlich, H.A.
J. Immunol. 141, 4024-4030, 1988
A;Title: Analysis of HLA-DP allelic sequence polymorphism using the in vitro enzymatic DNA amplification of DP-alpha and DP-beta loci.
A;Reference number: A92825; MUID:89035547; PMID:2460556
A;Accession: A30536
A;Molecule type: DNA
A;Residues: 35-121 <BUG1>
A;Cross-references: UNIPARC:UPI000008A59E; GB:M23675; NID:g188060; PIDN:AAA59740.1; PID:g553561
A;Experimental source: allele DPB4.1
R;Bugawan, T.L.; Angelini, G.; Larrick, J.; Auricchio, S.; Ferrara, G.B.; Erlich, H.A.
Nature 339, 470-473, 1989
A;Title: A combination of a particular HLA-DP beta allele and an HLA-DQ heterodimer confers susceptibility to coeliac disease.
A;Reference number: S04656; MUID:89262087; PMID:2498667
A;Contents: annotation
R;Lee, J.S.; Sartoris, S.; Briata, P.; Choi, E.; Cullen, C.; Lepaslier, D.; Yunis, I.
Immunogenetics 29, 346-349, 1989
A;Title: Sequence polymorphism of HLA-DP beta chains.
A;Reference number: I54458; MUID:89233301; PMID:2714855
A;Accession: I68752
A;Status: preliminary; translated from GB/EMBL/DDBJ
A;Molecule type: mRNA
A;Residues: 9-258 <LEE>
A;Cross-references: UNIPARC:UPI000008A66E; GB:M28202; NID:g575497; PIDN:AAA53197.1; PID:g575498
R;Bugawan, T.L.; Begovich, A.B.; Erlich, H.A.
Immunogenetics 32, 231-241, 1990
A;Title: Rapid HLA-DPB typing using enzymatically amplified DNA and nonradioactive sequence-specific oligonucleotide probes.
A;Reference number: I54472; MUID:91055805; PMID:2242906
A;Accession: I54472
A;Status: translated from GB/EMBL/DDBJ
A;Molecule type: DNA
A;Residues: 35-121 <BUG2>
A;Cross-references: UNIPARC:UPI000008A59E; GB:M62326; NID:g188012; PIDN:AAA59719.1; PID:g553542
C;Genetics:
A;Gene: GDB:HLA-DPB1; HLA-DP1B
A;Cross-references: GDB:120636; OMIM:142858
A;Map position: 6p21.3-6p21.3
A;Introns: 34/1; 122/1; 216/1; 253/1
A;Note: DPB1 is the only expressed DP beta gene
C;Superfamily: class II histocompatibility antigen; immunoglobulin homology
C;Keywords: glycoprotein; heterodimer; transmembrane protein
F;1-29/Domain: signal sequence #status predicted <SIG>
F;30-258/Product: class II histocompatibility antigen HLA-DP beta 1 chain #status predicted <MAT>
F;30-225/Domain: extracellular #status predicted <EXT>
F;30-121/Domain: beta-1 #status predicted <EX1>
F;137-202/Domain: immunoglobulin homology <IMM>
F;226-246/Domain: transmembrane #status predicted <TMM>
F;247-258/Domain: intracellular #status predicted <INT>
F;44-106,144-200/Disulfide bonds: #status predicted
F;48/Binding site: carbohydrate (Asn) (covalent) #status predicted
Query Match 98.4%; Score 1046; Length 258;
Best Local Similarity 99.0%;
Matches 194; Conservative 1; Mismatches 1; Indels 0; Gaps 0;
“Qy” is instantly recited SEQ ID NO: 3, while “Db” is the HLA-DP4 beta chain, position 112 and 141 amino acid residues are bolded and underlined.
Qy 1 RATPENYLFQGRQECYAFNGTQRFLERYIYNREEFARFDSDVGEFRAVTELGRPAAEYWN 60
Db 30 RATPENYLFQGRQECYAFNGTQRFLERYIYNREEFARFDSDVGEFRAVTELGRPAAEYWN 89
Qy 61 SQKDILEEKRAVPDRMCRHNYELGGPMTLQRRVQPRVNVSPSKKGPLQHHNWLVCHVTDF 120
Db 90 SQKDILEEKRAVPDRMCRHNYELGGPMTLQRRVQPRVNVSPSKKGPLQHHNLLVCHVTDF 149
Qy 121 YPGSIQVRWFLNGQEETAGVMSTNLIRNGDWTFQILVMLEMTPQQGDVYTCQVEHTSLDS 180
Db 150 YPGSIQVRWFLNGQEETAGVVSTNLIRNGDWTFQILVMLEMTPQQGDVYTCQVEHTSLDS 209
Qy 181 PVTVEWKAQSDSARSK 196
Db 210 PVTVEWKAQSDSARSK 225
Claims 1, 7, 80, 83, 89, 93, 98 and 101 are directed to an invention not patentably distinct from claims 4, 15, 19, 21-24, 61 and 63-66 of commonly assigned 17/631,820.
The U.S. Patent and Trademark Office may not institute a derivation proceeding in the absence of a timely filed petition. The USPTO normally will not institute a derivation proceeding between applications or a patent and an application having common ownership (see 37 CFR 42.411). Commonly assigned17/631,820, discussed above, may form the basis for a rejection of the noted claims under 35 U.S.C. 102 or 103 if the commonly assigned case qualifies as prior art under 35 U.S.C. 102(a)(2) and the patentably indistinct inventions were not commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention.
In order for the Examiner to resolve this issue the applicant or patent owner can provide a statement under 35 U.S.C. 102(b)(2)(C) and 37 CFR 1.104(c)(4)(i) to the effect that the subject matter and the claimed invention, not later than the effective filing date of the claimed invention, were owned by the same person or subject to an obligation of assignment to the same person. Alternatively, the applicant or patent owner can provide a statement under 35 U.S.C. 102(c) and 37 CFR 1.104(c)(4)(ii) to the effect that the subject matter was developed and the claimed invention was made by or on behalf of one or more parties to a joint research agreement that was in effect on or before the effective filing date of the claimed invention, and the claimed invention was made as a result of activities undertaken within the scope of the joint research agreement; the application must also be amended to disclose the names of the parties to the joint research agreement.
A showing that the inventions were commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention will preclude a rejection under 35 U.S.C. 102 or 103 based upon the commonly assigned case. Alternatively, applicant may take action to amend or cancel claims such that the applications, or the patent and the application, no longer contain claims directed to patentably indistinct inventions.
15. This is a new ground of rejection necessitated by Applicant’s amendment filed 3/30/26. Applicant has amended the claims and has added new claim 103.
Court rulings have been quite clear that ONLY DIVISIONAL applications are entitled to the shield from double patenting under 35 USC 121. Indeed, in AMGEN INC v. HOFFMANN LA ROCHE LTD GMBH LA (Nos. 2009-1020, 2009-1096) the court discusses this issue at length and states:
Turning to the legislative history, the court observed that a House Report also referred specifically to “divisional application[s].” Id. Notably absent from the legislative history, in the court's view, was a suggestion “that the safe-harbor provision was, or needed to be, directed at anything but divisional applications.” Id. at 1361. From there, the court “conclude^] that the protection afforded by section 121 to applications (or patents issued therefrom) filed as a result of a restriction requirement is limited to divisional applications.” Id. at 1362. Accordingly, the court decided that the § 121 safe harbor did not apply to the patent before it, which issued from a continuation-in-part application. Id.
We are persuaded by the reasoning in Pfizer that the § 121 safe harbor provision does not protect continuation applications or patents descending from only continuation applications. The statute on its face applies only to divisional applications, and a continuation application, like a continuation-in-part application, is not a divisional application.
Given that Applicant chose to file the 17/631,821 case that issued as US 12,590,139 as a separate unrelated application, not as a DIV of the instant application, the instant rejection has been set forth.
Claim 103 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 12,590,139 in view of Novak et al. (JCI, 1999, 104(12):R63-R67, of record).
The claims of US 12,590,139 are drawn to an HLA-DQ beta chain comprising an amino acid sequence with at least 80% identity to the amino acid sequence of SEQ ID NO: 3 (of US 12,590,139) and has 114W, 143M, 110Q, 116V, 118H and 146N relative to the position corresponding to the same amino acid position in SEQ ID NO: 3, an HLA class II molecule comprising the said DQ beta chain and a DQ alpha chain, nucleic acid molecule encoding the alpha or beta chain, cell comprising the HLA class II molecule, a complex comprising the HLA class II molecule and a peptide, or a DQ beta chain comprising the amino acid sequence set forth in SEQ ID NO: 4.
Note that SEQ ID NO: 3 recited in the claims of ‘139 is identical to instantly recited SEQ ID NO: 13 (instant claim 103 lacks antecedent basis in its base claim due to the presence of an asparagine (N) at position 146 rather than having glutamine at position 146 as is recited in the said base claim). Also note that SEQ ID NO: 4 recited in the claims of ‘139 also has the same substituent amino acid residues offset by the presence of a 17-mer signal sequence at the N-terminus of SEQ ID NO: 4 as opposed to SEQ ID NO: 3.
The claims of ‘139 do not recite wherein the HLA class II molecule comprising the said HLA-DQ alpha and beta chains and a cognate peptide are used in a method of identifying an MHC class II-specific TCR comprising contacting a CD4+ T cell with a complex comprising the MHC class II molecule and a peptide.
Novak et al. teach that soluble tetramerized class II HLA molecule loaded with an antigenic peptide and fluorescently labeled can be used to directly identify antigen-specific T cells from peripheral blood by contacting the HLA class II tetramers with the T cells and analyzing them by flow cytometry (i.e., selecting the T cells comprising a TCR, or “identifying an MHC class II specific TCR” on a T cell (e.g., abstract, Figure 3 and legend). Novak et al. teach that such a direct method advantageously avoids the need for limiting dilution analysis and permits simultaneous phenotypic analysis of the antigen-specific T cells using flow cytometry, and providing a means for understanding the immune response against infectious agents and in autoimmune disease (last paragraph of reference). See entire reference.
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have used the HLA-DQ/peptide complex that is recited in the claims of ‘139 as a tetramer to identify T cells having a cognate antigen-specific TCR as per the teaching of Novak et. al.
One of ordinary skill in the art would have been motivated to do this, and with a reasonable expectation of success in doing so, in order to identify cognate T cells for a different HLA class II molecule.
Claim 104 is are directed to an invention not patentably distinct from claims 1-14 of US 12,590,139. The U.S. Patent and Trademark Office may not institute a derivation proceeding in the absence of a timely filed petition. The USPTO normally will not institute a derivation proceeding between applications or a patent and an application having common ownership (see 37 CFR 42.411). Commonly assigned US 12,590,139, discussed above, may form the basis for a rejection of the noted claims under 35 U.S.C. 102 or 103 if the commonly assigned case qualifies as prior art under 35 U.S.C. 102(a)(2) and the patentably indistinct inventions were not commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention.
In order for the Examiner to resolve this issue the applicant or patent owner can provide a statement under 35 U.S.C. 102(b)(2)(C) and 37 CFR 1.104(c)(4)(i) to the effect that the subject matter and the claimed invention, not later than the effective filing date of the claimed invention, were owned by the same person or subject to an obligation of assignment to the same person. Alternatively, the applicant or patent owner can provide a statement under 35 U.S.C. 102(c) and 37 CFR 1.104(c)(4)(ii) to the effect that the subject matter was developed and the claimed invention was made by or on behalf of one or more parties to a joint research agreement that was in effect on or before the effective filing date of the claimed invention, and the claimed invention was made as a result of activities undertaken within the scope of the joint research agreement; the application must also be amended to disclose the names of the parties to the joint research agreement.
A showing that the inventions were commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention will preclude a rejection under 35 U.S.C. 102 or 103 based upon the commonly assigned case. Alternatively, applicant may take action to amend or cancel claims such that the applications, or the patent and the application, no longer contain claims directed to patentably indistinct inventions.
16. This is a new ground of rejection necessitated by Applicant’s amendment filed 3/30/26. Applicant has amended the claims and has added new claim 106.
Court rulings have been quite clear that ONLY DIVISIONAL applications are entitled to the shield from double patenting under 35 USC 121. Indeed, in AMGEN INC v. HOFFMANN LA ROCHE LTD GMBH LA (Nos. 2009-1020, 2009-1096) the court discusses this issue at length and states:
Turning to the legislative history, the court observed that a House Report also referred specifically to “divisional application[s].” Id. Notably absent from the legislative history, in the court's view, was a suggestion “that the safe-harbor provision was, or needed to be, directed at anything but divisional applications.” Id. at 1361. From there, the court “conclude^] that the protection afforded by section 121 to applications (or patents issued therefrom) filed as a result of a restriction requirement is limited to divisional applications.” Id. at 1362. Accordingly, the court decided that the § 121 safe harbor did not apply to the patent before it, which issued from a continuation-in-part application. Id.
We are persuaded by the reasoning in Pfizer that the § 121 safe harbor provision does not protect continuation applications or patents descending from only continuation applications. The statute on its face applies only to divisional applications, and a continuation application, like a continuation-in-part application, is not a divisional application.
Given that Applicant chose to file the 17/631,824 case as a separate unrelated application, not as a DIV of the instant application, the instant rejection has been set forth.
Claim 106 is provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 13, 45, 57, 59, 63, 79, 84, 85 and 94 of copending Application No. 17/631,824 in view of Novak et al. (JCI, 1999, 104(12):R63-R67, of record).
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The claims of 17/631,824 recite an HLA class II molecule comprising an HLA-DR beta chain comprising SEQ ID NO: 3 of ‘824 and further comprising an alpha chain, wherein the DR beta chain has an increased affinity for a CD4 protein as compared to a reference HLA class II molecule that comprises a DR beta chain comprising L114 and/or V143 of SEQ ID NO: 1 of ‘824; a cell comprising the HLA class II molecule, the molecule also comprising a peptide; a method of identifying a TCR capable of binding an epitope in an MHC class II complex comprising pulsing a cell comprising the HLA class II molecule complexed with a peptide epitope, and stimulating one or more CD4+ T cells with an APC, and a method of treating a disease or condition in a subject in need thereof, comprising administering the MHC class II/peptide complex comprising an epitope associated with a disease or condition is a cancer or an infection.
Note that SEQ ID NO: 3 recited in the claims of ‘824 is identical to instantly recited SEQ ID NO: 21 (instant dependent claim 106 lacks antecedent basis in its base claim 104 as it has 139K rather than 139T). Also note that SEQ ID NO: 4 recited in the claims of ‘824 is identical to instantly recited SEQ ID NO: 21 at amino acid residues 18-215 and thus meets the claim limitation recited in claim 106.
Novak et al. teach that soluble tetramerized class II HLA molecule loaded with an antigenic peptide and fluorescently labeled can be used to directly identify antigen-specific T cells from peripheral blood by contacting the HLA class II tetramers with the T cells and analyzing them by flow cytometry (i.e., selecting the T cells comprising a TCR, or “identifying an MHC class II specific TCR” on a T cell (e.g., abstract, Figure 3 and legend). Novak et. al. teach that such a direct method advantageously avoids the need for limiting dilution analysis and permits simultaneous phenotypic analysis of the antigen-specific T cells using flow cytometry, and providing a means for understanding the immune response against infectious agents and in autoimmune disease (last paragraph of reference). See entire reference.
It would have been prima facie obvious to one of ordinary skill in the art before the filing date of the claimed invention to have used the HLA-DR/peptide complex that is recited in the claims of ‘824 as a tetramer to identify T cells having a cognate antigen-specific TCR as per the teaching of Novak et al.
One of ordinary skill in the art would have been motivated to do this, and with a reasonable expectation of success in doing so, in order to identify cognate T cells for a different HLA class II molecule.
Claim 106 is are directed to an invention not patentably distinct from claims 1, 13, 45, 57, 59, 63, 79, 84, 85 and 94 of commonly assigned 17/631,824.
The U.S. Patent and Trademark Office may not institute a derivation proceeding in the absence of a timely filed petition. The USPTO normally will not institute a derivation proceeding between applications or a patent and an application having common ownership (see 37 CFR 42.411). Commonly assigned17/631,824, discussed above, may form the basis for a rejection of the noted claims under 35 U.S.C. 102 or 103 if the commonly assigned case qualifies as prior art under 35 U.S.C. 102(a)(2) and the patentably indistinct inventions were not commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention.
In order for the Examiner to resolve this issue the applicant or patent owner can provide a statement under 35 U.S.C. 102(b)(2)(C) and 37 CFR 1.104(c)(4)(i) to the effect that the subject matter and the claimed invention, not later than the effective filing date of the claimed invention, were owned by the same person or subject to an obligation of assignment to the same person. Alternatively, the applicant or patent owner can provide a statement under 35 U.S.C. 102(c) and 37 CFR 1.104(c)(4)(ii) to the effect that the subject matter was developed and the claimed invention was made by or on behalf of one or more parties to a joint research agreement that was in effect on or before the effective filing date of the claimed invention, and the claimed invention was made as a result of activities undertaken within the scope of the joint research agreement; the application must also be amended to disclose the names of the parties to the joint research agreement.
A showing that the inventions were commonly owned or deemed to be commonly owned not later than the effective filing date under 35 U.S.C. 100(i) of the claimed invention will preclude a rejection under 35 U.S.C. 102 or 103 based upon the commonly assigned case. Alternatively, applicant may take action to amend or cancel claims such that the applications, or the patent and the application, no longer contain claims directed to patentably indistinct inventions.
17. Claims 102 and 104 are allowed. Claims 1, 7, 80, 83, 89, 93, 98, 101, 103, 105 and 106 are rejected.
18. 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.
19. 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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the Examiner’s supervisor, MISOOK YU can be reached on 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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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