Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
DETAILED ACTION
1. Applicant’s amendment and response filed 6/20/25 is acknowledged and has been entered.
2. Applicant is reminded of Applicant's election of the species of bead carrier, HLA-A, carrier comprise b2m and HLA-A, peptide and encoding DNA for the peptide, and configuration of peptide-b2m-HLA-A in Applicant’s response filed 11/5/24.
Claims 13, 15 19-22, 24-28 and 31-34 read on the elected species.
Upon consideration of Applicant’s said amendment and the prior art, examination is being extended to the species recited in instant dependent claim 23.
Claims 13, 15, 19-28 and 31-34 are presently being examined.
3. Applicant’s amendment filed 6/20/25 has overcome the prior rejection of record of claims 13-22, 24-31, 33 and 34 under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Sepp et al (FEBS Lett. 2002, 532: 455-458, IDS reference) in view of Le Doussal et al (JIM, 2000, 241: 147-158, IDS reference), Brophy et al (J. Immunol. Meth. 2003, 272: 235-246, IDS reference), Luxembourg et al (Nature Biotechn. 1998, 16: 281-285, IDS reference), Ogg et al (AIDS, 1999, 13(14): 1991, IDS reference), and Brakmann, S (Angew. Chem. Int. Ed. 2004, 43: 5730-5734, IDS reference).
The art references do not teach the presently recited limitations. The primary art reference Sepp et al teaches only one gene (DNA)/bead, with multiple copies of the translated protein encoded by the DNA.
4. Applicant’s amendment filed 6/20/25 has overcome the prior rejection of record of claim 32 under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Sepp et al (FEBS Lett. 2002, 532: 455-458, IDS reference) in view of Le Doussal et al (JIM, 2000, 241: 147-158, IDS reference), Brophy et al (J. Immunol. Meth. 2003, 272: 235-246, IDS reference), Luxembourg et al (Nature Biotechn. 1998, 16: 281-285, IDS reference), Ogg et al (AIDS, 1999, 13(14): 1991, IDS reference), and Brakmann, S (Angew. Chem. Int. Ed. 2004, 43: 5730-5734, IDS reference) as applied to claims 13-22, 24-31, 33 and 34 above, and further in view of Stoeva et al (J. Am. Chem. Soc. 2006, 128: 8378-8379).
The art references do not teach the presently recited limitations. The primary art reference Sepp et al teaches only one gene (DNA)/bead, with multiple copies of the translated protein encoded by the DNA.
5. 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.
6. Claims 13, 15, 19-28 and 31-34 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 6/20/25.
a) Claim 13 is indefinite in the recitation of “exposing the peptide to a T-cell receptor in the presence of b2 microglobulin (b2m) and the MHC or MHC-like molecule” because it is not clear what is meant, i.e., the peptide, b2 microglobulin and the MHC or MHC-like molecule together with a tag are synthesized by IVTT as a single linked produce (i.e., as a single chain trimer with a tag) wherein the tag attaches the single linked product to the carrier. Consequently, the single chain timer with tag is already present.
b) Claim 21 is indefinite in the recitation of “wherein the T-cell receptor is expressed respectively by T cells” because it is not clear what is meant. The TCR alone is expressed by T cells.
c) Claim 23 is indefinite in the recitation of “wherein the MHC or MHC-like molecule is added exogenously to the peptide” because it is not clear what is meant, i.e., the MHC or MHC-like molecule is already present endogenously via its presence in a single chain trimer produced by IVTT.
d) Claim 29 is indefinite in the recitation of “exposing the peptide to a T-cell receptor in the presence of B2 microglobulin and the MHC or MHC-like molecule” because it is not clear what is meant, i.e., the peptide, B2 microglobulin and the MHC or MHC-like molecule together with a tag are synthesized by IVTT as a single linked produce (i.e., as a single chain trimer with a tag) wherein the tag attaches the single linked product to the carrier. Consequently, the single chain timer with tag is already present.
e) Claim 28 is indefinite in the recitation of “A method of identifying a peptide comprising detecting binding of the peptide to the T-cell receptor, wherein the bound peptide is identified by its encoding DNA” because it is not clear what is meant, i.e., the claim preamble states that the method is one of identifying a peptide, however, there is no active recited to identity the peptide, as the said “wherein” clause is not an active method step.
f) Claim 31 is indefinite in the recitation of “A method of identifying a peptide comprising…detecting binding of the peptide to the T-cell receptor, wherein the bound peptide is identified by its encoding DNA” because it is not clear what is meant, i.e., the claim preamble states that the method is one of identifying a peptide, however, there is no active recited to identity the peptide, as the said “wherein” clause is not an active method step.
g) Claim 13 is indefinite in the recitation of “A method to screen for a peptide which binds to a T-cell receptor and identify the peptide by its encoding DNA, the method comprising…recovering the encoding DNA of the peptide to identify the peptide” because it is not clear what is meant, i.e., the claim preamble recites that the method is one of identifying a peptide, however, there is no active step to identify the peptide, as “recovering the encoding DNA” dos not identify the peptide until a method step to identify it is recited.
7. 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.
8. The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
9. Claims 13, 15, 19-22, 24 and 25 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Nord et al (J. Biotechn., 2003, 106: 1-13) in view of Le Doussal et al (JIM, 2000, 241: 147-158, IDS reference), Diehl et al (Nature Protocols, 2006, 3(7): 551-559), and Luxembourg et al (Nature Biotechn. 1998, 16: 281-285, IDS reference).
This is a new ground of rejection necessitated by Applicant’s amendment filed 6/20/25.
Claim interpretation: As the instant specification discloses (e.g., at [0045] and [0046] that the peptide, MHC and/or b2m components of a MHC molecule may be connected via a peptide linker, the instant claims that recite that the component(s) is/are connected, are being interpreted as either connected via an interposed sequence or via fusion. The same is the case wherein the encoding DNA for the peptide is attached to the carrier, as the disclosure in the instant specification and the claims is intended to encompass direct or indirect attachment (see for example dependent claim 25 that recites “wherein the DNA comprises flanking nucleotide sequences that each bind to a forward primer and a reverse primer” as an example of indirect attachment to a carrier through an intervening sequence(s)). The specification does not provide a limiting or other definition for the limitation “recovering the encoding DNA of the peptide”. Nor does the specification provide a limiting definition for ‘identifying a peptide’ (although instances of the disclosure of identifying a peptide in the instant specification are followed by disclosure related to determining the sequence of DNA; for example, at [0022] the instant specification discloses that by identifying a peptide that is able to bind to a TCR the DNA which encodes the peptide can be readily recovered, amplified and sequenced and from said DNA sequence, the protein from which the peptide is derived may be deduced). Therefore, the limitation “identify the peptide” is being interpreted to encompass both recovering the encoding DNA of the peptide as a proxy for identifying the peptide or as alternatively, determining the sequence of the encoding DNA in order to identify the sequence of the peptide encoded by the DNA.
Nord et al teach use of um size beads as co-carriers of both genes and their corresponding protein products, with PCR product expression cassettes (DNA) (including biotinylated) immobilized onto beads (including streptavidin coated, streptavidin being a non-covalent binding partner for biotin) which are subsequently incubated with a [an in vitro] coupled cell-free transcription and translation extract (IVTT) to produce the corresponding protein. Nord et al teach that newly translated affinity-tagged protein become linked to the bead via bioaffinity principles through a cognate binding partner that has been pre-immobilized onto the bead which establishes a link between genotype (the DNA) and phenotype (the protein encoded by the DNA), with DNA sequencing identifying the particular phenotype attached to the bead. Nord et al teach that the beads can be incubated with a fluorescently-labeled target protein and analyzed and sorted by flow cytometry in a high-throughput manner. Nord et al teach that the bead format has already been extensively used in molecular biology applications for anchoring of nucleic acids or proteins by various means to preferentially paramagnetic beads. Nord et al teach another strategy for in vitro expression of microbead-anchored DNA expression cassettes for bioaffinity-mediated co-anchoring of encoded proteins based on the use of a water-in-oil emulsion to provide discrete compartments for cell-free transcription-translation reactions to reduce cross-binding effects. Nord et al teach that the cell-free system is advantageous over cell-based library methodologies in that a cell transformation step is not needed, introduction of genetic diversity into the library is facilitated, selections can be performed via flow cytometric sorting, including that ultrahigh-speed flow cytometric sortings are not detrimental to the physical integrity of the beads as opposed to cell-based library members with the result that very large libraries of beads can be screened and sorted in a reasonable time frame, and less stringent selection steps are facilitated in comparison to for example, use of yeast display libraries. (See entire reference, especially section 1 at the paragraph spanning columns 1-2 on page 2, Figure 1, last paragraph.)
Nord et al do not teach wherein the DNA encodes an MHC-binding peptide, that the corresponding tagged protein is a single chain trimer of the peptide, B2m and MHC heavy chain, nor wherein 1000 or more copies of the peptide and its encoding DNA are attached to the carrier.
Le Doussal et al teach engineering phage libraries comprising peptide-MHC complexes, wherein the library reflects different potential antigenic peptides that bind to the MHC, wherein the libraries are used to identify cognate membrane-bound or immobilized TCRs that bind to a particular peptide-MHC complex. Le Doussal et al exemplify a library comprising the murine H-2Kb class I MHC single chain molecule, in the following configuration: peptide-first amino acid linker sequence-MHC heavy chain-second amino acid linker sequence-2m. Le Doussal et al teach refolding strategy for MHC I/peptide complexes made in bacteria. Le Doussal et al teach that the use of phage display libraries comprising peptide-MHC complexes suffers from disadvantages, namely that the proportion of multimeric phages produced is not sufficient to allow direct detection of peptide-MHC complexes bound to [T] cells using flow cytometry, high density immobilized recombinant TCR must be used in screening (rather than T cells expressing a TCR), and phage display efficiency must be increased (see entire reference, especially abstract, introduction, and Fig. 1).
Diehl et al teach emulsion PCR for including beads comprising one PCR product bound thereto in a single compartment which after amplification by emulsion PCR, each compartment contains a bead that is coated with thousands of copies of the single DNA molecule originally present. Diehl et al teach that these beads can be recovered by magnet or by centrifugation, and that millions of beads can be analyzed within minutes using flow cytometry or optical canning instruments. Diehl et al teach that the DNA bound to such beads also provides excellent templates for high-throughput sequencing. Diehl et al teach that the DNA can comprise forward and reverse primers and that streptavidin-coated beads for example may attach biotin-tagged DNA. Diehl et al teach a variety of beads that may be used. (See entire reference, especially abstract, Figure 1 at the top).
Luxembourg et al teach that MHC class I molecules comprising a peptide epitope in the peptide binding site thereof can be attached via a tag to magnetic beads (i.e., non-covalently) and used to capture antigen-specific T cells, including low frequency T cells, as well as T cells with TCR of low affinity for the cognate antigen. Luxembourg et al teach that the T cells can be recovered and expanded after isolation on the MHC/bead constructs (see entire reference, especially abstract). Thus, Luxembourg et al teach that as early as 1998, it was possible to attach MHC class I/peptide complexes to beads via a tag, that these complexes were correctly folded and functioned to bind to cognate T cells. Luxembourg et al teach that they disposed the MCH complexes at high density to saturating amounts to achieve maximal T cell capture. See entire reference.
It would have been prima facie obvious to one of ordinary skill in the art before the time the invention was made to have comprised thousands of copies of one DNA PCR product comprising forward and reverse primers to the bead by emulsion PCR as is taught by Diehl et al in the method taught by the primary art reference Nord et al that comprises emulsion IVTT to produce the protein, and to have used encoding nucleic acid for single chain peptide/MHC I/2m with linkers disposed between the components thereof (i.e., it is a single chain trimer) as is taught by Le Doussal et al. It would have been prima facie obvious to one of ordinary skill in the art before the time the invention was made to have comprised the single chain MHC trimer at high density as is taught by Luxembourg et al. It would have been prima facie obvious to one of ordinary skill in the art before the time the invention was made to have used the beads to screen for T cells using flow cytometry and to have recovered the encoding DNA of the peptide on the bound beads and to have sequenced it as is taught by Nord et al for identifying the particular phenotype attached to the bead.
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 apply the cell-free system that links genotype to phenotype to an encoding DNA for a peptide and the phenotype comprising the peptide in the form of a single chain trimer construct of peptide/MHC/b2m for detecting a cognate TCR ligand on a T cell and identifying the sequence of the cognate peptide. One of ordinary skill in the art would have been motivated to do this in order to reap the advantages of the cell-free system taught by Nord et al versus the disadvantages of using a cell-based system (such as the phage display method taught by Luxembourg et al), e.g., a cell transformation step is not required, introduction of genetic diversity into the library is facilitated, selections can be performed via flow cytometric sorting (in contrast to the method taught by Luxembourg et al that employs high density of recombinant TCRs immobilized on a surface), selections can be performed via flow cytometric sorting, including that ultrahigh-speed flow cytometric sortings are not detrimental to the physical integrity of the beads as opposed to cell-based library members with the result that very large libraries of beads can be screened and sorted in a reasonable time frame, and less stringent selection steps are facilitated in comparison to for example, use of yeast display libraries. This is also the case in light of the teaching of Le Doussal et al that the use of phage display libraries comprising peptide-MHC complexes suffers from disadvantages, namely that the proportion of multimeric phages produced is not sufficient to allow direct detection of peptide-MHC complexes bound to [T] cells using flow cytometry, high density immobilized recombinant TCR must be used in screening (rather than T cells expressing a TCR), and phage display efficiency must be increased.
With regard to the limitation recited in instant base claim 13, “wherein 1000 or more copies of the peptide and its encoding DNA are attached to the carrier”, Diehl et al teach emulsion PCR for including beads comprising one PCR product bound thereto in a single compartment which after amplification by emulsion PCR, each compartment contains a bead that is coated with thousands of copies of the single DNA molecule originally present. Although the art references do not explicitly teach that 1000 or more copies of the peptide are present on the bead carrier, Luxembourg et al teach that it was possible to attach MHC class I/peptide complexes to beads at high density via a tag, and that these complexes were correctly folded and functioned to bind to cognate T cells; Luxembourg et al teach that they disposed the MCH complexes at high density to saturating amounts to achieve maximal T cell capture. Therefore, the claimed method appears to be similar to the method of the prior art absent a showing of unobvious differences. Since the Patent Office does not have the facilities for examining and comparing the method of the instant invention to those of the prior art, the burden is on Applicant to show an unobvious distinction between the method of the instant invention and that of the prior art. See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977).
Alternatively, it was well within the purview of one of ordinary skill in the art to determine saturating amounts of single chain peptide/MHC/b2m that are optimal to be disposed on different size bead carriers (i.e., this is a result effective variable).
Instant dependent claim 21 that recites “wherein the T-cell receptor is expressed…by T cells provided in a tissue sample”, is included in this rejection because T cells are isolated from blood which is a tissue.
10. Claims 26-28 and 31-34 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Nord et al (J. Biotechn., 2003, 106: 1-13) in view of Le Doussal et al (JIM, 2000, 241: 147-158, IDS reference), Diehl et al (Nature Protocols, 2006, 3(7): 551-559), and Luxembourg et al (Nature Biotechn. 1998, 16: 281-285, IDS reference) as applied to claims 15, 19-22, 24 and 25 above, and further in view of Brophy et al (J. Immunol. Meth. 2003, 272: 235-246, IDS reference) or Greten et al (J. Immun. Methods, 2002, 271: 125-135), and Stoeva et al (J. Am. Chem. Soc. 2006, 128: 8378-8379, of record).
This is a new ground of rejection necessitated by Applicant’s amendment filed 6/20/25.
The teachings and combination of Nord et al in view of Le Doussal et al, Diehl et al, and Luxembourg et al has been discussed above, hereafter referred to as the “combined references”.
The combined references do not teach wherein MHC is a human MHC comprising an HLA heavy chain that is HLA-A, HLA-B, or HLA-C, nor that the configuration of the single chain MHC molecules is peptide-linker-b2m-linker-MHC heavy chain.
Brophy et al teach using phage display comprising single chain MHC class I molecules from random or natural peptides for probing binding of cognate T cells. Brophy et al teach mouse such MHC class I complexes such as H-2Kb or human MHC class I complexes, wherein the three human MHC class I heavy chains are HLA-A (including HLA-A2), HLA-B and HLA-C allele products. Brophy et al teach several configurations of MHC constructs including the configurations recited in the instant claims: peptide-linker-2m-linker-heavy chain of MHC and peptide-linker-MHC heavy chain-linker-2m, and that these constructs can be used attached to yeast, for a yeast display technology to identify and isolate TCRs that bind to MHC/peptide complexes (i.e., they are able to interact with the attached peptide to put the peptide into a conformation such that it can be presented to a T cell) Brophy et al teach flexible peptide linkers interposed between components. Brophy et al teach that it is known in the art how to produce these constructs and fold them so that they are stable and can bind the attached peptide. Brophy et al exemplify constructs comprising the murine H-2Kb class I MHC single chain molecule. Brophy et al reference Le Doussal et al for phage libraries comprising peptide-MHC complexes, wherein the library reflects different potential antigenic peptides that bind to the MHC (see entire reference, especially abstract, introduction, section 2.1, first sentence at col 2 on page 244, first para at col 2 on page 236, col 1 on page 236 at the first full para to col 2, first full paragraph on pages 236 at column 2, Bjorkman et al entry in the references section).
Alternatively, Greten et al teach a single chain trimer of HLA-A2 in the configuration peptide-linker-b2m-HLA-A2 heavy chain ECD (see entire reference)
It would have been prima facie obvious to one of ordinary skill in the art before the time the invention was made to have used any human HLA molecule of interest, including HLA-A, HLA-B, or HLA-C, including HLA-A2, that is known in the art as taught by Brophy et al or the HLA-A2 construct taught by Greten et al on the bead in the method taught by the combined references.
One of ordinary skill in the art would have been motivated to do this in order to identify peptides bound by such HLA molecules that can bind to cognate T cells of interest, and to investigate TCR repertoires.
The combined references do not teach wherein the copies of the encoding DNA are attached covalently to the surface of the carrier.
Stoeva et al provide such a teaching as they teach a gold (Au) nanoparticle bead having an antibody that recognizes a target protein and also having a covalently attached barcode DNA (i.e., chemically attached to the nanoparticle via HS and wherein the barcode DNA comprises a universal sequence identical for all the different barcodes as well as a unique target reporting portion). Stoeva et al teach that the nanoparticles can be isolated with a magnetic field and washed, and the barcode DNA release by a ligand exchange process induced by the addition of DTT. Stoeva et al teach that oligonucleotide-functionalized gold nanoparticles [comprising a target recognition protein element] have a demonstrated advantage over conventional probes in biodetection schemes as a result of their unique chemical and physical properties, and constitute a powerful amplification and detection system that is highly sensitive (see entire reference, especially Scheme 1 and the paragraph spanning pages 8378-8379).
It would have been prima facie obvious to one of ordinary skill in the art before the time the invention was made to have covalently attached the encoding DNA of the combined references to the bead as is taught by Stoeva et al.
One of ordinary skill in the art would have been motivated to do this in order to make and use a magnetic nanoparticle in identifying or screening a peptide, and with a reasonable expectation of success in doing so since magnetic nanoparticles having both protein and DNA disposed thereon were known in the art as indicated by the combined references and by Stoeva et al, and were taught by Stoeva et al to be a preferred nanoparticle for biodetection in terms of enabling magnetic separation and in terms of sensitivity.
11. 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.
12. 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 14/908,511 case that issued as US 10,351,847 as a separate unrelated application, not as a DIV of the instant application, the instant rejection has been set forth.
Claims 13, 15, 19-22, 24-28 and 31-34 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 10,351,847 (of record) in view of Nord et al (J. Biotechn., 2003, 106: 1-13), Le Doussal et al (JIM, 2000, 241: 147-158, IDS reference), Diehl et al (Nature Protocols, 2006, 3(7): 551-559), Luxembourg et al (Nature Biotechn. 1998, 16: 281-285, IDS reference), Brophy et al (J. Immunol. Meth. 2003, 272: 235-246, IDS reference) or Greten et al (J. Immun. Methods, 2002, 271: 125-135), and Stoeva et al (J. Am. Chem. Soc. 2006, 128: 8378-8379, of record).
This is a new ground of rejection necessitated by Applicant’s amendment filed 6/20/25.
Claim interpretation: As the instant specification discloses (e.g., at [0045] and [0046] that the peptide, MHC and/or b2m components of a MHC molecule may be connected via a peptide linker, the instant claims that recite that the component(s) is/are connected, are being interpreted as either connected via an interposed sequence or via fusion. The same is the case wherein the encoding DNA for the peptide is attached to the carrier, as the disclosure in the instant specification and the claims is intended to encompass direct or indirect attachment (see for example dependent claim 25 that recites “wherein the DNA comprises flanking nucleotide sequences that each bind to a forward primer and a reverse primer” as an example of indirect attachment to a carrier through an intervening sequence(s)). The specification does not provide a limiting or other definition for the limitation “recovering the encoding DNA of the peptide”. Nor does the specification provide a limiting definition for ‘identifying a peptide’ (although instances of the disclosure of identifying a peptide in the instant specification are followed by disclosure related to determining the sequence of DNA; for example, at [0022] the instant specification discloses that by identifying a peptide that is able to bind to a TCR the DNA which encodes the peptide can be readily recovered, amplified and sequenced and from said DNA sequence, the protein from which the peptide is derived may be deduced). Therefore, the limitation “identify the peptide” is being interpreted to encompass both recovering the encoding DNA of the peptide as a proxy for identifying the peptide or as alternatively, determining the sequence of the encoding DNA in order to identify the sequence of the peptide encoded by the DNA.
Claims 1-13 and 20-22 of US 10,351,847 are drawn to a carrier comprising multiple copies of a single peptide attached covalently or non-covalently to the surface of the carrier, multiple copies of DNA encoding the peptide also attached covalently or non-covalently to the surface of the carrier at separate sites from those of the peptides, and including wherein the peptide is attached to b2m either fused or via a linker sequence, and including wherein the carrier is a solid support. The carrier may be a bead.
Claims 14-16 of US 10,351,847 are drawn to a library containing a plurality of carriers of claim 1.
Claims 17-19 of US 10,351,847 are drawn to a method to identify a peptide ligand for a molecule comprising providing the library of claim 14 and exposing the library to the molecule, recovering the peptide or its encoding DNA from the carrier which bound to the molecule.
The claims of US 10,351,847 do not recite wherein the peptide-linker-b2m also comprises an HLA-A, -B or -C heavy chain, nor that the method screens for or identifies a peptide that binds to a particular TCR, including by sequencing the recovered DNA encoding the peptide, including wherein the DNA comprises flanking nucleotide sequences that bind to a forward primer and a reverse primer, nor that the carrier/single chain MHC with peptide/encoding DNA-tag for the peptide and library thereof comprises 1000 or more copies of the peptide and its encoding DNA attached to the carrier, wherein the DNA is generated by in vitro PCR, nor sequencing the DNA encoding the peptide after said DNA is recovered.
The teachings and combination of the references cited herein have been enunciated above in this office action, hereafter referred to as the “combined references”. The said teachings and combination thereof will not be repeated herein, except as follows.
Nord et al in view of Le Doussal et al, Diehl et al, and Luxembourg et al provide the teachings and motivation to combine to produce a method for screening for and identifying a peptide that binds to a TCR comprising, providing the recited carrier to which is non-covalently attached a peptide as a single chain construct (peptide-linker-MHC-linker-b2m) produced in emulsion via IVTT and to which is also attached an encoding DNA for the cognate peptide in the single chain construct, wherein 1000 or more copies of the peptide and its encoding DNA are attached to the carrier, and for sequencing the DNA encoding the peptide after it is recovered from the carrier that binds to a cognate TCR on a T cell. It would have been prima facie obvious to one of ordinary skill in the art before the time the invention was made to have incorporated these features into the carrier and method recited in the claims of US 10,351,847. One of ordinary skill in the art would have been motivated to do this in order to reap the advantages taught by these said references in using a cell-free system that possesses these said features.
Brophy et al or Greten et al teach a variety of human MHC class I molecules, including HLA-A, -B, or -C, including HLA-A2, as well as an alternative single chain MHC molecule configuration (peptide-linker-b2m-linker-MHC heavy chain), and Stoeva et al teach covalent attachment of barcode DNA corresponding to a protein specificity to a bead carrier.
It would have been prima facie obvious to one of ordinary skill in the art before the time the invention was made to have used any single chain MHC molecule of interest, including in any configuration taught by the art references in the carrier and method of using the carrier recited in the claims of ‘847. 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 peptides that bind to said MHC molecules of interest, and to identify cognate T cells as the claims of ‘847 are silent as to the molecule on the cell that is being bound (TCR on a cell in this instance), and Le Doussal et al and Brophy et al teach that a single chain MHC class I molecule in a library format can be used to bind cognate T cells.
It would have been prima facie obvious to one of ordinary skill in the art before the time the invention was made to have the attachment means by Stoeva et al to link the DNA to the carrier in the claims of ‘847. One of ordinary skill in the art would have been motivated to use any suitable attachment means, and with a reasonable expectation of success in doing so.
Claims 13, 15, 19-22, 24-26, 28 and 31-34 are directed to an invention not patentably distinct from claims 1-22 of commonly assigned US 10,351,847, as enunciated above.
The U.S. Patent and Trademark Office normally will not institute an interference between applications or a patent and an application of common ownership (see MPEP Chapter 2300). Commonly assigned US 10,351,847, discussed above, may form the basis for a rejection of the noted claims under pre-AIA 35 U.S.C. 102 or 103(a) if the commonly assigned case qualifies as prior art under pre-AIA 35 U.S.C. 102(e), (f) or (g) and the patentably indistinct inventions were not commonly owned at the time the claimed invention in this application was made. In order for the examiner to resolve this issue the assignee can, under pre-AIA 35 U.S.C. 103(c) and 37 CFR 1.78(g), either show that the patentably indistinct inventions were commonly owned at the time the claimed invention in this application was made, or name the prior inventor of the subject matter at issue.
A showing that the inventions were commonly owned at the time the claimed invention in this application was made will preclude a rejection under pre-AIA 35 U.S.C. 103(a) based upon the commonly assigned application that qualifies as a reference under pre-AIA 35 U.S.C. 102(e), (f) or (g). 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.
13. No claim is allowed.
14. 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.
15. 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
/MICHAEL SZPERKA/Primary Examiner, Art Unit 1641