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 .
Claim Status
Claims 1 – 2, 4 – 5, 7 – 16, 18, 35 – 39 are pending.
Claim Objections
Claim 9 is objected to in the recitation of “60% identity” and in the interest of improving claim form, it is suggested that the noted phrase be amended to recite “60% sequence identity.”
Claim 12 is objected to because of the following informalities: In claim 12, line 2, “BRC” should read “RBC”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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.
Claims 1, 4, 5, 7, 8, 11, 12, 16 and 38 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Regarding claims 1, 4 and 7, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claims 4, 7, 11 and 16, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claims 11 and 16, the phrase "for example" renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claims 5, 8 and 38 recites the limitation “the glycine(n) and/or lysine ε-amino group at internal sites of the extracellular domain of at least one endogenous, non-engineered membrane protein of a red blood cell” in lines 1-3. There is insufficient antecedent basis for this limitation in the claim.
Claims 5, 8 and 38 are indefinite in the recitation of “glycine(n)” because it is unclear as to what “(n)” represents in the noted term. It is suggested that the applicant recite the intended meaning of “(n)” in claims 5, 8 and 38. In the interest of clarity, it is noted that claim 5 recites “optionally n being 1 or 2,” however, this description of “(n)” is optional and non-limiting.
Claim 12 is indefinite in the recitation of “on the surface of the RBC” in line 2. Claim 1 does not require the endogenous, non-engineered membrane protein of an RBC to be on the surface of the RBC.
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.
Claims 1 – 2, 5, 7 – 8, 12 – 16 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Swee et al. (WO 2014/183066 A2; cited on the IDS; hereafter “Swee”) in view of Williamson Daniel J et al. (Depsipeptide substrates for sortase-mediated N-terminal protein ligation, Nat Protoc, 09.Jan.2014 (09.01.2014), pp. 253 – 262; cited on the IDS; hereafter “Williamson”).
Regarding instant claims 1 and 2, claim 1 of Swee recites a method of conjugating an agent to an animal cell, the method comprising: contacting an animal cell with a sortase substrate that comprises a sortase recognition sequence and an agent in the presence of a sortase under conditions suitable for the sortase to conjugate the sortase substrate to an endogenous, non-engineered polypeptide expressed by the animal cell. Also, Swee teaches that the conjugated cells include red blood cells (p. 98, paragraph [0169]). Swee differs from claim 1 mainly in that: the sortase recognition motif comprising an unnatural amino acid located at position 5 optionally substituted hydroxyl carboxylic acid having formulae of CH2OH- (CH2)n-COOH. However, Williamson (Abstract, FIG. 1) discloses the sortase recognition sequence comprising LPET-CH2OHCOOH-G can effectively render the reaction irreversible.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the methods of Swee and the motif of Williamson together to improve sortase substrate conjugation in regard to red blood cells (RBC) by making the reaction irreversible.
Regarding instant claims 5 and 8, claim 2 of Swee recites the method of claim 1, wherein the sortase substrate is conjugated to an extracellular portion of an endogenous, non-engineered polypeptide expressed by the cell. Swee teaches sortase can be used for modification of eukaryotic cell surfaces without requiring that the cells be engineered to express polypeptides comprising a sortase recognition sequence or nucleophilic acceptor sequence, noting that such polypeptides may comprise a sequence of one or more glycines exposed at the cell surface, e.g., in an N-terminal domain, available to act as a nucleophile in a reaction in which sortase is used to conjugate a sortase substrate to the polypeptide (p. 56, paragraph [0066]).
Regarding instant claim 7, Swee teaches the cell surfaces can be modified without requiring that the cells be engineered to express polypeptides comprising a sortase recognition sequence or nucleophilic acceptor sequence (p. 56, paragraph [0066]).
Regarding instant claim 12, Swee teaches the exemplary sortase recognition motifs LPXTGG and LPETGG (p. 44, paragraph [0053]) and shows a representation of a sortase-modified cell (pp. 60-61, paragraph [0080]).
Regarding instant claim 13, Swee teaches the cells of interest include red blood cells (p. 98, paragraph [0169]) and teaches examples of sortase-mediated conjugation of red blood cells with various agents modified to comprise a sortase recognition sequence (Examples 28-32 beginning at p. 259).
Regarding instant claims 14 – 16, Swee teaches a composition comprising the red blood cell of claim 13 and in some embodiments, sortase-modified cells can be administered prophylactically (p. 230, para. [00423]) and used as vehicles for delivery of therapeutic agents (p. 98, para. [00169]) with the aid of “pharmaceutically acceptable carriers” (p.240, para. [00442]) for viruses (p. 156, para. [00267]), tumors (p.160, para. [00274]), lysosomal storage diseases (p.136 para. [00233]), inflammatory and autoimmune diseases (p. 138, para. [00237]). Also, Swee teaches the use of “sortagged” mammalian cells for the purpose of diagnosing disease (p. 65, para. [0092]; pp. 167 – 168, paras. [00288] and [00290]).
Regarding instant claim 18, Swee teaches the average circulation time or plasma half-life may be increased (pp. 65-66, para. [0093]).
Claims 9 – 11 are rejected under 35 U.S.C. 103 as being unpatentable over Swee and Williamson as applied to claims 1 – 2, 5, 7 – 8, 12 – 15 and 18 above, and further in view of Chen et al. (CN 109797194 A; hereafter “Chen”).
Swee and Williamson teach all limitations of claims 1 – 2, 5, 7 – 8, 12 – 15 and 18 as described in the previous rejection but do not teach a sequence comprising SEQ ID 3.
Regarding instant claims 9 – 10, Chen teaches a sequence identical to instant SEQ ID 3 (SEQ ID NO: 1 of Chen is identical to instant SEQ ID NO: 3).
Chen teaches S. aureus sortase mutant 1 comprising the mutations P94R/D124G/D160N/D165A/Y187L/E189R/K190E/K196T/F200L (Translation at p. 3, middle) and referred to as “mgSrtA” (Translation at p. 4, third full paragraph). Chen teaches mgSrtA can bind a molecule comprising a LPXTG sequence to the cell membrane surface (Translation at p. 4, first paragraph). Chen teaches the surface of the cell membrane has few oligo glycines and mgSrtA exhibits greatly improved marking efficiency at single glycine residues on the surface of the cell membrane (Translation at p. 4, last paragraph).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to use the mgSrtA of Chen in the method of Swee. Doing so would greatly improve sortase conjugation efficiency at single glycine residues on the surface of the cell membrane.
Regarding instant claim 11, Swee teaches a wide variety of agents may be conjugated (p. 2, paragraph [0007]) and claim 20 of Swee recites the agent comprises an amino acid, a peptide, a protein, a polynucleotide, a carbohydrate, a tag, a metal atom, a chelating agent, a contrast agent, a catalyst, a polymer, a recognition element, a small molecule, a lipid, a label, an epitope, an antigen, a therapeutic agent, a cross-linker, a toxin, a radioisotope, an antibody, an antibody domain, a click chemistry handle, a virus, a cell, or a particle, and Chen teaches a labeling molecule including a small molecule or a biological macromolecule such as biotin, fluorescent dye, enhanced and green fluorescent protein (eGFP) (Translation at p. 4, first full paragraph).
Claims 4 and 35 – 39 are rejected under 35 U.S.C. 103 as being unpatentable over Swee, Williamson, and Chen as applied to claims 9 – 11 above, and further in view of Qin et al. (US 2017/0112944 A1; hereafter “Qin”).
Regarding instant claims 4 and 35 – 39, Swee teaches in certain embodiments, chemical modification of cells includes introducing a reactive functional group, such as a sulfhydryl or maleimide to cell surfaces (p. 36, paragraph [0045]). Swee teaches the polypeptide modified by the sortase is an integral membrane protein or a peripheral membrane protein (p. 63, paragraph [0088]). Swee teaches the function of cysteine (p. 43, paragraph [0052]) as the catalytic residue in the enzyme’s active site in which it serves as a nucleophile to cleave a peptide bond in the motif. Swee does not explicitly disclose 6-Maleimidohexanoic acid.
Qin discloses the use of sortase (paragraph [0056]) and 6-maleimidohexanoic acid (paragraph [0063]) in the preferred chemical conjugation moiety (CCA) for their coupling agent. The flexibility (six carbon chain) and heterobifunctional nature of 6-Maleimidohexanoic acid makes it an ideal spacer/linker for sortase conjugation. These characteristics of 6-Maleimidohexanoic acid are crucial for achieving controlled and directed conjugation. The cells of interest (RBC), motif of claim 37, and the sortase conjugation of claim 38 have been discussed above in the rejections of claims 1 and 5, respectively. Swee teaches sortase-mediated lysine side chain conjugation (p. 64, paragraph [0091]). Also, the mutant sortase amino acid sequence of claim 39 has been discussed in the rejection of claims 9 and 10.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the methods of Swee, the motif of Williamson, and the mutant sortase of Chen with the linker of Qin for antibody-drug conjugates. Doing so would improve sortase-mediated conjugation in regard to red blood cells (RBC). The spacer of Qin makes the motif more suitable for use in sortase substrate conjugation. Swee provides methods for sortase-catalyzed reactions for the modification of proteins expressed by living cells, Williamson provides the irreversible reaction motif, Chen teaches the benefit of using the mutant S. aureus sortase, and Qin teaches the use of 6-Maleimidohexanoic acid for a stable antibody-drug conjugate.
Claim Rejections - Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 5, 7, 9 – 12 and 18 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 13 – 15, 17 – 19, 21, 22 and 39 of co-pending application 17/906,435 (reference application) in view of Swee and Williamson.
Regarding instant claims 1, 2, 5, 9 and 10, claim 13 of the reference application recites a method for covalently modifying the glycine(n) and/or lysine ԑ-amino group at internal sites of the extracellular domain of at least one endogenous, non-engineered membrane protein of a red blood cell (RBC), comprising contacting the RBC with a sortase substrate that comprises a sortase recognition motif and an agent, in the presence of a sortase under conditions suitable for the sortase to conjugate the sortase substrate to the glycine(n) and/or lysine ԑ-amino group at internal sites of the extracellular domain of the at least one endogenous, non-engineered membrane protein of the RBC by a sortase-mediated reaction, wherein the sortase-mediated reaction comprises a sortase-mediated glycine conjugation and/or a sortase- mediated lysine side chain s-amino group conjugation, wherein the sortase is a Staphylococcus aureus transpeptidase A variant (mgSrtA) comprising the mutations of P94R/S, D124G, D160N, D165A, Y187L, E189R, K190E, K196T and F200L and optionally E105K and/or E108A/Q, wherein the numbering of the mutations is according to the numbering of SEQ ID NO: 1.
Regarding the difference between the reference application and the instant application, the reference application does not mention a motif with an unnatural amino acid. Claim 13 differs from claim 1 mainly in that: the sortase recognition motif comprising an unnatural amino acid located at position 5 optionally substituted hydroxyl carboxylic acid having formulae of CH2OH- (CH2)n-COOH. However, Williamson (Abstract, FIG. 1) discloses the sortase recognition motif comprising LPET-CH2OHCOOH-G, as stated above renders the reaction irreversible.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the methods of the reference application, Swee, and the motif of Williamson together to improve sortase substrate conjugation in regard to red blood cells (RBC).
Regarding instant claims 1 and 2, Claim 19 of the reference application recites the method of claim 13, wherein the sortase substrate comprises the sortase recognition motif on its C-terminus, and optionally the sortase recognition motif comprises an amino acid sequence selected from the group consisting of LPXTG, LPXAG, LPXSG, LPXLG, LPXVG, LGXTG, LAXTG, LSXTG, NPXTG, MPXTG, IPXTG, SPXTG, VPXTG, YPXRG, LPXTS and LPXTA, wherein X is any amino acid.
Regarding instant claim 5, Claim 14 of the reference application recites the method of claim 13, wherein the sortase-mediated glycine conjugation and/or the sortase-mediated lysine side chain s-amino group conjugation occur at least on glycine(n) and/or lysine s-amino group at internal sites of the extracellular domain of the at least one endogenous, non-engineered membrane protein, optionally n being 1 or 2, wherein the at least one endogenous, non-engineered membrane protein include a native RBC membrane protein with UniProt ID selected from the following: CASR, CD3G, DSCL1 , TRPC2, C209B , ITCH, AKA12, ITIH4, ATP4A, P2RX1, RYR3, C163A, AMER1 , MRCKB, ELMO1, DESP, CD40L, S12A2, ADCY6, CY24B, MNAR1 and PLXC1.
Regarding instant claim 9, claim 17 of the reference application recites the method of claim 13, wherein the sortase is a Staphylococcus aureus transpeptidase A variant (mgSrtA), wherein the mgSrtA comprises an amino acid sequence having at least 60% identity to the amino acid sequence as set forth in SEQ ID NO: 3, and comprises the mutations of P94R/S, D124G, D160N, D165A, Y187L, E189R, K190E, K196T and F200L and optionally E105K and/or E108A/Q, wherein the numbering of the mutations is according to the numbering of SEQ ID NO: 1.
Regarding instant claim 10, claim 18 of the reference application recites the method of claim 17, wherein the mgSrtA comprises the amino acid sequence as set forth in SEQ ID NO: 3 or SEQ ID NO: 27.
Regarding instant claim 7, claim 15 of the reference application recites the method of claim 13, wherein the RBC has not been genetically engineered to express a protein comprising a sortase recognition motif or a nucleophilic acceptor sequence, and optionally the RBC is a natural RBC a natural human RBC.
Regarding instant claim 11, claim 21 of the reference application recites the method of claim 13, wherein the agent comprises a binding agent, a therapeutic agent, or a detection agent, optionally the agent comprises a peptide comprising an extracellular domain of oligomeric ACE2.
Regarding instant claim 12, claim 22 of the reference application recites the method of claim 13, wherein the covalently modified at least one endogenous, non-engineered membrane protein on the surface of the RBC comprises a structure of Al-LPXT- P1, in which LPXT is linked to a glycine(n) in P1, and/or a structure of A1-LPXT-P2, in which LPXT is linked to the side chain s-amino group of lysine in P2, wherein n is 1 or 2, Al represents the agent, P1 and P2 independently represent the at least one endogenous, non- engineered membrane protein, and X represents any amino acids.), claim 12 of the reference application recites the method of claim 1, wherein the covalently modified at least one membrane protein on the surface of the BRC comprises a structure of A1-L1-P1, in which L1 is linked to a glycine(n) in P1, and/or a structure of A1-L1-P2 in which L1 is linked to the side chain ε-amino group of lysine in P2, wherein n is 1 or 2; A1 represents the agent; L1 is selected from the group consisting of LPXT, LPXA, LPXS, LPXL, LPXV, LGXT, LAXT, LSXT, NPXT, MPXT, IPXT, SPXT, VPXT, and YPXR; P1 and P2 independently represent the at least one membrane protein; and X represents any amino acid.
Regarding instant claim 18, claim 39 of the reference application recites The method of claim 13, wherein the method increases the circulation time or plasma half-life of the agent in a subject.
Therefore, claims 1, 2, 5, 7, 9 – 12 and 18 of this application are unpatentable over claims 13 – 15, 17 – 19, 21, 22 and 39 of the reference application in view of Swee, Williamson. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 2, 4, 5, 7, 8, 9, 10, 12 and 14 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 2, 3, 5, 13, 14, 17 18 and 24of co-pending application 18/264,098 (reference application).
Regarding instant claims 1, 2, 5 and 10, claim 18 of the reference application recites a method for preparing the red blood cell of claim 1, comprising contacting a red blood cell (RBC) with a sortase substrate that comprises a sortase recognition motif and an agent, in the presence of a sortase under conditions suitable for the sortase to conjugate the sortase substrate to the at least one endogenous, non-engineered membrane protein of the RBC by a sortase-mediated reaction, optionally by a sortase-mediated glycine conjugation and/or a sortase-mediated lysine side chain ε-amino group conjugation, wherein the agent comprises a uric acid degrading polypeptide,
wherein the sortase substrate comprises a structure of (A1-Sp)m-M, in which A1 represents an agent, Sp represents the optional spacer, and M represents a sortase recognition motif; m being an integer greater than or equal to 1, optionally m=1 to 3,
wherein the sortase recognition motif comprises or consists essentially of or consists of an amino acid sequence selecting from a group consisting of LPXTG, LPXAG, LPXSG, LPXLG, LPXVG, LGXTG, LAXTG, LSXTG, NPXTG, MPXTG, IPXTG, SPXTG, VPXTG, YPXRG, LPXTS and LPXTA, wherein X is any amino acid,
optionally wherein the sortase recognition motif comprises an unnatural amino acid located at position 5 from the direction of N-terminal to C-terminal of the sortase recognition motif, wherein the unnatural amino acid is an optionally substituted hydroxyl carboxylic acid having a formulae of CH2OH-(CH2)-COOH, n being an integer from 0 to 3, optionally n=0,
optionally wherein M comprises or consists essentially of or consists of an amino acid sequence selecting from a group consisting of LPXT*Y, LPXA*Y, LPXS*Y, LPXL*Y, LPXV*Y, LGXT*Y, LAXT*Y, LSXT*Y, NPXT*Y, MPXT*Y, IPXT*Y, SPXT*Y, VPXT*Y and YPXR*Y, wherein * represents the optionally substituted hydroxyl carboxylic acid; and X and Y independently represent any amino acid,
optionally wherein M comprises or consists essentially of or consists of an amino acid sequence selecting from a group consisting of LPXT*G, LPXA*G, LPXS*G, LPXL*G, LPXV*G, LGXT*G, LAXT*G, LSXT*G, NPXT*G, MPXT*G, IPXT*G, SPXT*G, VPXT*G, YPXR*G, LPXT*S and LPXT*A, optionally M is LPET*G with * being 2-hydroxyacetic acid.
Regarding instant claim 4, claim 14 and 24 of the reference application recites the red blood cell of any of claim 5, wherein the Sp is selected from a group consisting of the following types: (1) zero-length type; (2) aminesulfhydryl type; (3) homobifunctional NHS esters type; (4) homobifunctional imidoesters type; (5) carbonyl-sulfydryl type; (6) sulfhydryl reactive type; and (7) sulfhydryl-hydroxy type; optionally the one or more Sp is an NHS ester-maleimide heterobifunctional crosslinker, or such as 6-Maleimidohexanoic acid, and 4-Maleimidobutyric acid, and the agent comprises an exposed sulfydryl, preferably optionally an exposed cysteine, optionally a terminal cysteine, optionally a C-terminal cysteine.
Regarding instant claim 7, claim 3 of the reference application recites the red blood cell of claim 1, wherein the RBC has not been genetically engineered to express a protein comprising a sortase recognition motif or a nucleophilic acceptor sequence, and optionally, the RBC is a natural RBC, or a natural human RBC.
Regarding instant claim 8, claim 2 of the reference application recites the red blood cell of claim 1, wherein the sortase-mediated glycine conjugation and/or the sortase-mediated lysine side chain ɛ-amino group conjugation occur at least on glycine(m) and/or lysine ɛ-amino group at internal sites of the extracellular domain of the at least one endogenous, non-engineered membrane protein, optionally n being 1 or 2.
Regarding instant claim 9, claim 5 of the reference application recites the red blood cell of claim 1, wherein the sortase is a Sortase A (SrtA) or a Staphylococcus aureus transpeptidase A variant (mgSrtA), optionally wherein the mgSrtA comprises or consists essentially of or consists of an amino acid sequence having at least 60% identity to an amino acid sequence as set forth in SEQ ID NO: 3.
Regarding instant claim 12, claim 13 of the reference application recites the red blood cell of claim 1, wherein the agent linked to the at least one endogenous, non-engineered membrane protein on the surface of the BRE RBC comprises a structure of (A¹-Sp)m-L'-P¹, in which L¹ is linked to a glycine(m) in P¹, and/or a structure of (A¹-Sp)m-L¹-P2, in which L¹ is linked to the side chain ɛ-amino group of lysine in P²,wherein n is 1 or 2, A¹ represents the agent, Sp represents the optional spacer, Lis selected from the group consisting of LPXT, LPXA, LPXS, LPXL, LPXV, LGXT, LAXT, LSXT, NPXT, MPXT, IPXT, SPXT, VPXT, and YPXR, P¹ and P2 independently represent the extracellular domain of the at least one endogenous, non-engineered membrane protein, and X represents any amino acids; m being an integer greater than or equal to 1, optionally m=1 to 3.
Regarding instant claim 14, claim 17 of the reference application recites a composition comprising a plurality of the red blood cells of any of claim 1 and a physiologically acceptable carrier.
Therefore, claims 1, 2, 5 and 10 of the instant application are unpatentable over claim 18 and claims 4, 7, 8, 9, 12 and 14 of the instant application are unpatentable over claims 2, 3, 5, 13, 14, 17 and 24 of the reference application. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
The invention as claimed is prima facie obvious over Swee, in view of Williamson, Chen, and Qin. No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WALTER JACKSON III whose telephone number is (571)272-0247. The examiner can normally be reached Monday - Friday 9:00 AM - 5:00 PM.
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/WALTER JACKSON III/Examiner, Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638