DETAILED ACTION
Status of the Claims
Claims 1-26 are pending.
Claims 14-16 and 19-23 are withdrawn as being drawn to a non-elected invention.
Claims 1-13, 17-18, and 24-26 are examined herein.
Applicant’s election of Group I (claims 1-13, 17-18, and 24-26) in the reply filed on 06/29/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claim Interpretation
For the purposes of patent examination, pending claims are given their broadest reasonable interpretation consistent with the ordinary and customary meaning of the term and must be consistent with the use of the claim term in the specification and drawings. Additionally, an applicant is entitled to be their own lexicographer by clearly setting forth a definition of the term. Therefore, where an explicit definition is provided by the applicant for a term, that definition will control interpretation of the term as it is used in the claim. In the present case, the terms “mechanically linked”, “chemically linked”, and “functionally linked” are used throughout the claims. These terms are defined in the instant specification on pages 241-240. As such, these terms will be interpreted by the provided definitions for the purposes of examination, as follows:
Functionally linked: Functionally linked shall mean any form of linkage that keeps two molecules within a maximum distance from each other, i.e. the two molecules are kept within given spatial boundaries. Functionally linked molecules include chemically linked molecules as well as mechanically linked molecules.
Mechanically linked: Mechanically linked shall for the purpose of this invention mean that the molecules in question - e.g., an encoding molecule (e.g., a DNA molecule) and a peptide that is encoded by said encoding molecule - are held in the vicinity of each other by physical rather than chemical means. Thus, if two molecules are said to be mechanically linked it is a physical boundary that keep the molecules from separating.
Chemically linked: Chemically linked shall solely denote covalently linked and non-covalently linked molecules.
Claim 13 further limits the RNA of claim 1. However, neither claim 1 nor claim 13 requires that the encoding molecule is RNA. Therefore, the broadest reasonable interpretation of claim 13 further limits the encoding molecule of claim 1, if that encoding molecule is RNA. However, other encoding molecules are not further limited by claim 13.
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 7 and 24-26 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. Each of these claims These claims are all dependent on claim 1 and therefore incorporate all limitations recited in claim 1.
Claim 7 states that “each pMHC complex is functionally linked to a human cell, a yeast cell, or a bacterial cell”. However, the pMHC complexes of claim 1 are stated as being mechanically linked to an encoding molecule “within a phage particle”. Therefore, claim 7 would require the pMHC complexes are both mechanically linked to an encoding molecule in a phage particle, and functionally linked to a cell. The specification discloses each of these limitations individually, but not in one combination and therefore there is not adequate written description of this claim.
Claims 24-26 are drawn to a composition for and a method of screening T-cells by a proximity extension assay approach using pMHC multiplexers. However, claim 1 recites the composition of pMHC multiplexers as comprising an encoding molecule “comprised within a phage particle”. Therefore, the presently rejected claims require encoding molecules comprised within separate phage particles to have complementary nucleotides and to form a duplex. The specification does not disclose this combination of limitations and therefore there is not adequate written description of these claims.
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.
Claims 1-13, 17-18, and 24-26 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.
Claims 1, 4, 7, 11, 13, and 25 recite “such as”, which renders the scope unclear as it does not reasonably assert whether the recited values or features following that phrase are required limitations. For example, claim 4 recites “comprising 10,000 or more pMHC Multiplexers, such as 100,000 or more pMHC Multiplexers, such as 1,000,000 or more pMHC Multiplexers.” It is unclear whether the claim covers compositions having at least 10,000 pMHC Multiplexers generally, or instead is limited in some way by the later recited values. Hence, the metes and bounds of the claim are unascertainable. See MPEP 2173.05(d). For the purposes of examination, any “such as” limitation will be considered optional and therefore not limiting.
Claim 6 recites the limitation of a “chemical entity” that is “not found in natural peptides made up of the 20 natural amino acids”. This limitation clearly excludes the 20 natural amino acids from being the “chemical entity”, but it is unclear whether additional moieties that may be found on a “natural peptide” are similarly excluded, such as biotin, phosphate groups, or glycosyl groups. For the purposes of examination, the “chemical entity” will be interpreted as being any entity except for one of the 20 natural amino acids.
Claim 26 is indefinite for reciting limitations that are unclear because they are not compatible with the limitations of the claim upon which they depend. As previously discussed in section 7b, this claim requires encoding molecules comprised within separate phage particles to form a duplex. As hybridization of the encoding molecules is precluded by their physical occlusion into separate phages, formation of a duplex would be impossible and therefore this claim is indefinite.
Claims 2-3, 5, 8-10, 12, and 24 depend from claim 1 and are therefore similarly rejected.
Claim Rejections - 35 USC § 102
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.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Dogan et al.
Claims 1, 3-5, 8-11, and 17-18 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Dogan et al. (Eur. J. Immunol. (2004), 34: 598-607).
Regarding claims 1, 4, 5, 8, and 13, Dogan discloses a composition of 10 or more pMHC multiplexers (p. 602, section 2.4, 2nd ¶; p. 600, section 2.2, 2nd ¶: 3 amino acid positions randomized in each of two libraries, which were then combined = ~104 multiplexers) that comprise a virus particle (p. 600, section 2.2, 2nd ¶: “peptide library phages”), wherein each multiplexer comprises a unique encoding molecule (DNA, p. 604, section 4.1) comprised within a phage particle (Fig. 7), and being mechanically linked to two or more unique pMHC complexes (Fig. 7C), where the peptide of the pMHC complex is encoded by the encoding molecule (Fig. 7: peptide sequence). Additionally, the pMHC complex is non-covalently linked to a phage coat protein (Fig. 7C: Human Β2m∷MHC heavy chain).
Regarding claims 3 and 9-11, Dogan further discloses that the unique encoding molecule is of non-human origin, is a virus-specific epitope, and comprises 8 amino acids (p. 602, section 2.4, 2nd ¶: VSV; Table 2).
Regarding claims 17-18, Dogan further discloses a screening process involving the disclosed composition of pMHC multiplexers (p. 602, section 2.4, 2nd ¶: “biopanning”) and the screening process involves flow cytometry (p. 605, section 4.5).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Dogan et al. and Mai-Prochnow et al.
Claim 2 is rejected under 35 U.S.C. 103 as being unpatentable over Dogan et al. in view of Mai-Prochnow et al. (FEMS Microbiol. Rev. (2015), 39: 465-487). Dogan discloses the limitations of claim 1 as discussed previously. Additionally, Dogan discloses that the phage is a filamentous phage but does not explicitly state which (Introduction; Fig. 7). However, it is likely an fd bacteriophage based on the vectors used (p. 604, section 4.1). Therefore the difference between the instant claim and Dogan is that the instant claim requires an M13 phage, while Dogan discloses a generic filamentous phage that is potentially an fd phage.
Mai-Prochnow teaches (p. 466, 1st ¶) that the E. coli Ff filamentous phages are “closely related phages f1, fd, and M13”. Additionally, Mai-Prochnow teaches that their genomes are 98.5% identical and are “used interchangeably” in “molecular biology applications”. Mai-Prochnow later (p. 480, col. 2, 1st full ¶) discloses that one of these applications of Ff phages is phage display for “identification of rare desirable variants of antibodies, proteins or short peptides in large libraries”. This establishes that the M13 and fd phages are recognized as equivalent in the prior art for the purpose of phage display and it is considered prima facie obvious to substitute equivalents known for the same purpose, per MPEP 2144.06. Therefore, it would have been obvious to one of ordinary skill in the art by the effective filing date to substitute the generic/fd phage of Dogan with M13 phage.
Dogan et al., Mai-Prochnow et al., and Love et al.
Claims 6 is rejected under 35 U.S.C. 103 as being unpatentable over Dogan et al. in view of Mai-Prochnow et al. as applied to claim 2, and further in view of Love et al. (ChemBioChem (2006), 7: 753-756)). Dogan discloses all limitations of claim 1 as previously discussed. Additionally, Dogan discloses that the pMHC complex is chemically linked to a phage (Fig. 7C). As discussed above with regard to claim 2, the phage being filamentous phage M13 is obvious over the disclosures of Dogan and Mai-Prochnow. However, Dogan does not disclose that the chemical link comprises a chemical entity that is not one of the natural 20 amino acids.
Dogan also teaches that “the affinity of the peptide for the MHC seems to influence the stability of the P/MHC formed at the surface of the phages” (p. 599, Section 2.1, 2nd ¶). Dogan therefore teaches that the multiplexer is limited by the stability of the pMHC complex and would not be useful for screening peptides that have lower affinity for MHC. In order to rectify this problem identified by Dogan, one of ordinary skill in the art would recognize that by covalently attaching MHC to the phage surface, the interaction between the peptide and MHC would be enhanced by increasing its local concentration.
Love discloses a complex where two interacting moieties are attached to the surface of a phage, one being expressed as a fusion with a coat protein and the other covalently attached to the coat protein via a genetically-encoded selenocysteine (Scheme 1). Though intended for enzyme-substrate interactions, one of ordinary skill in the art would recognize that the selenocysteine attachment could be adapted to pMHC complex formation, thereby providing a covalent attachment of MHC to the phage and increasing the stability of the pMHC complex.
Therefore, it would have been obvious to one of ordinary skill in the art by the effective filing date to apply the known technique of Love to the pMHC multiplexers of Dogan, because covalently attaching MHC to the phage would be an improvement resulting in a stabilized pMHC complex. This application would have yielded predictable results because the coupling chemistry is “compatible with a wide variety of functional groups” (p. 755, col. 2, full ¶) and “can be easily adapted for any display technology” (p. 756), as taught by Love.
Dogan et al. and Pederson et al.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Dogan et al. in view of Pederson et al. (U.S. PGPub 2018/0180601 A1). Dogan discloses all limitations of claim 1 as previously discussed. Dogan does not disclose that the unique peptide is derived from the proteomes of adenovirus, retrovirus, herpes simplex virus, vaccinia virus, or influenza virus.
Pederson discloses that the peptide is derived from the proteome of the retrovirus HIV (p. 47, ¶[0899]). Pederson also teaches that the peptide being derived from HIV is useful for mapping immune reactivity to viruses, providing motivation for one of ordinary skill to incorporate peptides derived from HIV to the method of Dogan. Furthermore, there would be a reasonable expectation of success in doing so as Pederson also discloses pMHC complexes linked to phages (p. 30, ¶[0613]). Therefore, it would have been obvious to one of ordinary skill by the effective filing date to incorporate the HIV-derived peptides of Pederson to the pMHC multiplexers of Dogan, based on the motivation provided by Pederson, with a reasonable expectation of success.
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.
Application No: 18/263,281
Claims 1-5, 8-10, and 12-13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1-6 and 8-11 of copending Application No. 18263281 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because they disclose substantially overlapping subject matter.
Claims 1, 2, and 8 are not patentably distinct from claims 1 and 6 of the reference application.
Claims 3-5 is not patentably distinct from claims 2, 4, and 5 of the reference application, respectively.
Claims 9, 10, 12, and 13 are not patentably distinct from claims 8, 9, 10, and 11 of the reference application.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Relevant Prior Art
Oller-Salvia et al., "Efficient Phage Display with Multiple Distinct Non-Canonical Amino Acids Using Orthogonal Ribosome-Mediated Genetic Code Expansion". Angewandte Chemie International Edition (2019), 58: 10844-10848.
Conclusion
No claims are allowed.
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/ALEXANDRA OLSON/Examiner, Art Unit 1684
/JEREMY C FLINDERS/Primary Examiner, Art Unit 1684
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