The finality of the rejection of the last Office action is withdrawn and replaced by instant Office action.
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
RESPONSE TO AMENDMENT
Status of Application/Amendments/claims
Applicant’s amendment filed April 7, 2026, September 11, 2026 and September 18, 2026 is acknowledged. Claims 2-4, 6, 9-16 and 18-28 are canceled. Claims 1, 5, 7, 8 and 17 are pending in this application. Claims 19-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. was treated as without traverse in the reply filed on October 28, 2025.
3. Claims 1, 5, 7, 8 and 17 are under examination in this office action.
4. Applicant’s arguments filed on April 7, 2026, September 11, 2026 and September 18, 2026 have been fully considered but they are not deemed to be persuasive for the reasons set forth below.
New Grounds of Rejection Necessitated by the Amendment
The following rejections are new grounds of rejections necessitated by the amendment filed on April 7, 2026, September 11, 2026 and September 18, 2026
Claim Rejections - 35 USC § 103
5. 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1, 5, 8 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Guyon et al. (US8252743; also published as WO2008065372). The reference of The rejection is reinstated and maintained for the reasons of record and the reasons set forth below.
Claims 1, 5, 8 and 17 as amended are drawn to a polypeptide comprising the sequence of SEQ ID NO:1.
Briefly, Guyon et al. (US8252743) teach a modified EPO polypeptide comprising K20Q and having the amino acid sequence of SEQ ID NO:19 (which is 99.1% identical to instant SEQ ID NO:1; see the sequence alignment below), and additional one or more amino acid modifications at position K45 and K97 including K45Q and K97Q (see claims 8, 12-13; col. 8, lines 54-62, col. 9, lines 9 and 16; col. 89, table 5). Guyon also teaches a fusion protein comprising the modified EPO polypeptide and a histidine tag in claim 5 (col. 113, lines 42-56) or a maltose binding protein sequence (col. 114, line 20-28), and a composition comprising the modified EPO (see col. 14, lines 1-67). The modified EPO polypeptide disclosed by Guyon comprising 166 amino acid residues in length, which is the same size as in SEQ ID NO:1, and thus lacks the native carbohydrate moiety as in claim 8 in view of paragraphs [0081]-[0082] and [0220] of the instant specification (based on the published application).
While Guyon does not explicitly teach that the additional modifications are exactly two K45Q and K97Q, Guyon teaches additional one or more amino acid modifications at position K45 and K97 including K45Q and K97Q for the modified EPO polypeptide comprising K20Q and having the amino acid sequence of SEQ ID NO:19 and that the modification of K20Q, and/or K45Q and/or K97Q still maintain the activity of EPO and increase resistance to proteolysis and stability of the EPO (see col. 6, lines 38, 46, 49, 55; col.7, lines 15,21; col. 8, lines 21, 24, 30; col.9, lines6,9, 16; col. 57, lines 22-25; col. 64, lines 4, line8, 14; Table 3).
A person of ordinary skill in the art would have recognized that selecting and applying the known modification of K45Q and K97Q at positions K45 and K97 of EPO, and the known technique disclosed by Guyon to the Guyon’s modified EPO polypeptide comprising K20Q and SEQ ID NO:19 (K20Q, and K45 and K97) would have yielded the predictable result of the claimed polypeptide comprising instant SEQ ID NO:1 (i.e. K20Q, K45Q and K97K) and resulted in an improved product for increasing resistance to proteolysis and stability of EPO.
Using and including the known modification of K45Q and K97Q at positions K45 and K97 of EPO in the Guyon’s modified EPO polypeptide comprising K20Q and SEQ ID NO:19 (K20Q, and K45 and K97) would increase resistance to proteolysis and stability of the Guyon’s modified EPO polypeptide, and expand application of the Guyon’s modified EPO polypeptide for therapeutic purpose, and would increase patients’ satisfaction with treatment using the Guyon’s modified EPO polypeptide because modifications of K45Q and K97Q at positions K45 and K97 of EPO in the Guyon’s modified EPO polypeptide comprising K20Q and SEQ ID NO:19 (K20Q, and K45 and K97) would increase resistance to proteolysis and stability of EPO and prolong the half-life of the EPO for therapeutic purposes.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known modification of K45Q and K97Q at positions K45 and K97 of EPO, and the known technique disclosed by Guyon to the Guyon’s modified EPO polypeptide comprising K20Q and SEQ ID NO:19 (K20Q, and K45 and K97), and yield the predictable result of a polypeptide comprising instant SEQ ID NO:1 (i.e. K20Q, K45Q and K97K).
SEQ ID NO:1
US-11-998-387A-19
Sequence 19, US/11998387A
Patent No. 8252743
GENERAL INFORMATION
APPLICANT: Thierry Guyon
APPLICANT: Gilles Borrelly
APPLICANT: Xavier Gallet
APPLICANT: Lila Drittanti
APPLICANT: Manuel Vega
TITLE OF INVENTION: MODIFIED ERYTHROPOIETIN POLYPEPTIDES AND USE THEREOF FOR TREATMENT
FILE REFERENCE: 119365-00049/931
CURRENT APPLICATION NUMBER: US/11/998,387A
CURRENT FILING DATE: 2009-02-25
PRIOR APPLICATION NUMBER: 60/861,615
PRIOR FILING DATE: 2006-11-28
NUMBER OF SEQ ID NOS: 310
SEQ ID NO 19
LENGTH: 166
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: EPO_17_K20Q
Query Match 99.1%; Score 843; Length 166;
Best Local Similarity 98.8%;
Matches 164; Conservative 2; Mismatches 0; Indels 0; Gaps 0;
Qy 1 APPRLICDSRVLERYLLEAQEAENITTGCAEHCSLNENITVPDTQVNFYAWKRMEVGQQA 60
||||||||||||||||||||||||||||||||||||||||||||:|||||||||||||||
Db 1 APPRLICDSRVLERYLLEAQEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQA 60
Qy 61 VEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDQAVSGLRSLTTLLRALGAQKEAIS 120
||||||||||||||||||||||||||||||||||||:|||||||||||||||||||||||
Db 61 VEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAIS 120
Qy 121 PPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR 166
||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR 166
SEQ ID NO:1
Sequence 37, US/11998387A
Patent No. 8252743
GENERAL INFORMATION
APPLICANT: Thierry Guyon
APPLICANT: Gilles Borrelly
APPLICANT: Xavier Gallet
APPLICANT: Lila Drittanti
APPLICANT: Manuel Vega
TITLE OF INVENTION: MODIFIED ERYTHROPOIETIN POLYPEPTIDES AND USE THEREOF FOR TREATMENT
FILE REFERENCE: 119365-00049/931
CURRENT APPLICATION NUMBER: US/11/998,387A
CURRENT FILING DATE: 2009-02-25
PRIOR APPLICATION NUMBER: 60/861,615
PRIOR FILING DATE: 2006-11-28
NUMBER OF SEQ ID NOS: 310
SEQ ID NO 37
LENGTH: 166
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: EPO_35_K45Q
Query Match 99.1%; Score 843; Length 166;
Best Local Similarity 98.8%;
Matches 164; Conservative 2; Mismatches 0; Indels 0; Gaps 0;
Qy 1 APPRLICDSRVLERYLLEAQEAENITTGCAEHCSLNENITVPDTQVNFYAWKRMEVGQQA 60
|||||||||||||||||||:||||||||||||||||||||||||||||||||||||||||
Db 1 APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTQVNFYAWKRMEVGQQA 60
Qy 61 VEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDQAVSGLRSLTTLLRALGAQKEAIS 120
||||||||||||||||||||||||||||||||||||:|||||||||||||||||||||||
Db 61 VEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAIS 120
Qy 121 PPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR 166
||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR 166
SEQ ID NO:1
US-11-998-387A-79
Sequence 79, US/11998387A
Patent No. 8252743
GENERAL INFORMATION
APPLICANT: Thierry Guyon
APPLICANT: Gilles Borrelly
APPLICANT: Xavier Gallet
APPLICANT: Lila Drittanti
APPLICANT: Manuel Vega
TITLE OF INVENTION: MODIFIED ERYTHROPOIETIN POLYPEPTIDES AND USE THEREOF FOR TREATMENT
FILE REFERENCE: 119365-00049/931
CURRENT APPLICATION NUMBER: US/11/998,387A
CURRENT FILING DATE: 2009-02-25
PRIOR APPLICATION NUMBER: 60/861,615
PRIOR FILING DATE: 2006-11-28
NUMBER OF SEQ ID NOS: 310
SEQ ID NO 79
LENGTH: 166
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: EPO_77_K97Q
Query Match 99.1%; Score 843; Length 166;
Best Local Similarity 98.8%;
Matches 164; Conservative 2; Mismatches 0; Indels 0; Gaps 0;
Qy 1 APPRLICDSRVLERYLLEAQEAENITTGCAEHCSLNENITVPDTQVNFYAWKRMEVGQQA 60
|||||||||||||||||||:||||||||||||||||||||||||:|||||||||||||||
Db 1 APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQA 60
Qy 61 VEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDQAVSGLRSLTTLLRALGAQKEAIS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 VEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDQAVSGLRSLTTLLRALGAQKEAIS 120
Qy 121 PPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR 166
||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR 166
Response to Amendment
On p. 12-13 of the response filed 04/07/2026, Applicant argues that Guyon fails to teach a polypeptide having the sequence of instant SEQ ID NO:1 or 7 recited in amended claims 1 and 7.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2141, MPEP2141-I, rationales identified by the Court in KSR (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, 82 USPQ2d 1385 (2007)), MPEP2141-II, the basic factual inquires of Graham v. John Deere Co.(Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966)),and MPEP §2141.01-2147.03, the cited references do render the claimed invention obvious because:
Guyon teach a modified EPO polypeptide comprising K20Q and having the amino acid sequence of SEQ ID NO:19, which is 99.1% identical to instant SEQ ID NO:1 and comprises K20Q (see the sequence alignment), and wherein the modified EPO polypeptide comprises additional one or more amino acid modifications at position K45 and K97 including K45Q and K97Q (see claims 8, 12-13; col. 8, lines 54-62, col. 9, lines 9 and 16; col. 89, table 5). Guyon also teaches a fusion protein comprising the modified EPO polypeptide and a histidine tag in claim 5 (col. 113, lines 42-56) or a maltose binding protein sequence (col. 114, line 20-28), and a composition comprising the modified EPO (see col. 14, lines 1-67).
While Guyon does not explicitly teach that the additional modifications are exactly two K45Q and K97Q, Guyon teaches additional one or more amino acid modifications at position K45 and/or K97 including K45Q and K97Q on the modified EPO polypeptide comprising K20Q and the amino acid sequence of SEQ ID NO:19 disclosed by Guyon can still maintain the activity of EPO, and increase resistance to proteolysis and stability of the EPO (see col. 6, lines 38, 46, 49, 55; col.7, lines 15,21; col. 8, lines 21, 24, 30; col.9, lines6,9, 16; col. 57, lines 22-25; col. 64, lines 4, line8, 14; Table 3).
A person of ordinary skill in the art would have recognized that selecting and applying the known modification of K45Q and K97Q at positions K45 and K97 of EPO, and the known technique disclosed by Guyon to the Guyon’s modified EPO polypeptide comprising K20Q and SEQ ID NO:19 (K20Q, and K45 and K97) would have yielded the predictable result of the claimed polypeptide comprising instant SEQ ID NO:1 (i.e. K20Q, K45Q and K97K) and resulted in an improved product for increasing resistance to proteolysis and stability of EPO.
Using and including the known modification of K45Q and K97Q at positions K45 and K97 of EPO in the Guyon’s modified EPO polypeptide comprising K20Q and SEQ ID NO:19 (K20Q, and K45 and K97) would increase resistance to proteolysis and stability of the Guyon’s modified EPO polypeptide, and expand application of the Guyon’s modified EPO polypeptide for therapeutic purpose, and would increase patients’ satisfaction with treatment using the Guyon’s modified EPO polypeptide because modifications of K45Q and K97Q at positions K45 and K97 of EPO in the Guyon’s modified EPO polypeptide comprising K20Q and SEQ ID NO:19 (K20Q, and K45 and K97) would increase resistance to proteolysis and stability of EPO and prolong the half-life of the EPO for therapeutic purposes.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known modification of K45Q and K97Q at positions K45 and K97 of EPO, and the known technique disclosed by Guyon to the Guyon’s modified EPO polypeptide comprising K20Q and SEQ ID NO:19 (K20Q, and K45 and K97), and yield the predictable result of a polypeptide comprising instant SEQ ID NO:1 (i.e. K20Q, K45Q and K97K).
Accordingly, the rejection of claims 1, 5, 8 and 17 under 35 U.S.C. 103 as being unpatentable over Guyon (US8252743) is maintained.
Conclusion
Allowable Subject Matter
6. Claim 7 is allowed.
7. Claims 1, 5, 8 and 17 are rejected.
8. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Sathyanesan et al. (Transl. Psychi. 2018; 8:113. DOI 10.1038/s41398-018-0168-9) teaches carbamoylated erthropoietin (CEPO) and its effects on inducing expression of BDNF, VGF, Arc, TH and neuritrin in medial prefrontal cortex (mPFC) and hippocampal subfield and potential use for treatment of cognitive dysfunction in neuropsychiatric diseases (see abstract) and that the positions K45 and K20 are in close proximity to the high affinity active site residues and K97 is the only carbamoylated lysine that is close to the low affinity site (see p. 10, discussion).
Guyon et al. (WO2008065372) teach a modified EPO polypeptide comprising the sequence of SEQ ID NO:79, which is 99.1% identical to instant SEQ ID NO:1 (see the sequence alignment below),wherein the modified EPO polypeptide contains one or more amino acid replacements including K20Q, K45Q and K97Q (see col. 62, lines 50-60; col.63, line 3; col. 64, lines 4; 8; 14, table 3; col. 66, lines 63, 66; col. 67, line 5; 29-35; col. 69, line 9-15). Guyon teaches a fusion protein comprising the modified EPO polypeptide and a maltose binding protein sequence in claim 4 (col. 114, line 20-28), a histidine tag in claim 5 (col. 113, lines 42-56) or a composition comprising the modified EPO (see col. 14, lines 1-67).
SEQ ID NO:1
ARW15606
(NOTE: this sequence has 3 duplicates in the database searched)
ID ARW15606 standard; protein; 166 AA.
XX
AC ARW15606;
XX
DT 07-AUG-2008 (first entry)
XX
DE Human modified erythropoietin (EPO) protein SEQ ID:19.
XX
KW diagnostic test; therapeutic; protein stabilization; protein therapy;
KW protein production; protein detection; mutagenesis; cytokine; anemia;
KW seizure disorder; multiple sclerosis; cerebral ischemia; hypotension;
KW cardiac arrest; ischemia; myocardial infarction; inflammation;
KW cognitive disorder; radiation injury; cerebral palsy;
KW neurodegenerative disease; Alzheimers disease; Parkinsons disease;
KW Leigh disease; hiv associated dementia; amnesia;
KW amyotrophic lateral sclerosis; alcoholism; mood disorder;
KW anxiety disorder; attention deficit hyperactivity disorder;
KW schizophrenia; autism; creutzfeldt jakob disease; trauma; brain injury;
KW spinal cord injury; head injury; macular degeneration; neuropathy;
KW diabetic neuropathy; diabetic retinopathy; glaucoma; ocular disease;
KW renal failure; cancer; vulnerary; vasotropic; tranquilizer;
KW ophthalmological; nootropic; neuroprotective; neuroleptic; nephrotropic;
KW muscular-gen.; hypertensive; cytostatic; cns-gen.; cerebroprotective;
KW cardiant; antiparkinsonian; antiinflammatory; anti-hiv; antidiabetic;
KW antianemic; antialcoholic; anticonvulsant; erythropoietin; EPO; mutein.
XX
OS Homo sapiens.
OS Synthetic.
XX
CC PN WO2008065372-A2.
XX
CC PD 05-JUN-2008.
XX
CC PF 27-NOV-2007; 2007WO-GB004520.
XX
PR 28-NOV-2006; 2006US-0861615P.
XX
CC PA (NAUT-) NAUTILUS BIOTECH SA.
XX
CC PI Guyon T, Borrelly G, Gallet X, Drittanti L, Vega M;
XX
DR WPI; 2008-H01039/44.
XX
CC PT New pharmaceutical composition comprises modified therapeutic polypeptide
CC PT or an active fragment of the polypeptide in a vehicle, useful for
CC PT treating disease or condition, e.g. anemia, seizure disorder,
CC PT hypotension, or inflammation.
XX
CC PS Claim 89; SEQ ID NO 19; 272pp; English.
XX
CC The present invention relates to novel modified erythropoietin (EPO)
CC polypeptides and other modified therapeutic polypeptides such as
CC granulocyte macrophage-colony stimulating factor (GM-CSF); macrophage-
CC colony stimulating factor (M-CSF); granulocyte colony-stimulating factor
CC (G-CSF); leukemia inhibitory factor (LIF); interleukin 1beta (IL-1beta);
CC interleukin-2 (IL-2); interleukin-3 (IL-3); interleukin-4 (IL-4);
CC interleukin-5 (IL-5); interleukin-6 (IL-6); oncostatin M (OSM); stem cell
CC factor (SCF); interferon-beta (IFN-beta) and interferon-gamma (IFN-
CC gamma). The polypeptides are modified to exhibit physical properties and
CC activities that differ from the corresponding unmodified polypeptides and
CC nucleic acid molecules encoding these polypeptides also are provided. The
CC invention provides methods for treatment and diagnosis using these
CC therapeutic polypeptides and also discloses a pharmaceutical composition
CC which comprises a modified therapeutic polypeptide or its active
CC fragment. The modified therapeutic polypeptide of the invention comprises
CC one or more amino acid replacements, insertions and deletions and
CC modifications at one or more of glycosylation sites compared to the
CC unmodified therapeutic polypeptide; exhibits increased resistance to
CC proteolysis; is not glycosylated and exhibits therapeutic activity. Also
CC claimed is a modified Erythropoietin (EPO) polypeptide; a nucleic acid
CC molecule encoding the modified EPO polypeptide; a vector comprising the
CC nucleic acid molecule which is linked to a promoter; a eukaryotic or a
CC prokaryotic host cell consisting of the nucleic acid molecule or the
CC vector which is useful for the production of a modified EPO polypeptide
CC and a method for expressing a modified EPO polypeptide which comprises
CC detection of the modified EPO polypeptide. The invention further
CC discloses that the modified therapeutic polypeptide is a cytokine and it
CC is present in the precursor or mature form. The pharmaceutical
CC composition of the invention is useful for diagnosing and treating
CC diseases such as anemia, seizure disorder, multiple sclerosis, cerebral
CC ischemia, hypotension, cardiac arrest, ischemia, myocardial infarction,
CC inflammation, cognitive disorder, radiation injury, cerebral palsy,
CC neurodegenerative disease, Alzheimers disease, Parkinsons disease, Leigh
CC disease, hiv associated dementia, amnesia, amyotrophic lateral sclerosis,
CC alcoholism, mood disorder, anxiety disorder, attention deficit
CC hyperactivity disorder, schizophrenia, autism, creutzfeldt jakob disease,
CC trauma, brain injury, spinal cord injury, head injury, macular
CC degeneration, neuropathy, diabetic neuropathy, diabetic retinopathy,
CC glaucoma, ocular disease, renal failure and cancer. The present sequence
CC is a Human modified erythropoietin (EPO) protein.
XX
SQ Sequence 166 AA;
Query Match 99.1%; Score 843; Length 166;
Best Local Similarity 98.8%;
Matches 164; Conservative 2; Mismatches 0; Indels 0; Gaps 0;
Qy 1 APPRLICDSRVLERYLLEAQEAENITTGCAEHCSLNENITVPDTQVNFYAWKRMEVGQQA 60
||||||||||||||||||||||||||||||||||||||||||||:|||||||||||||||
Db 1 APPRLICDSRVLERYLLEAQEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQA 60
Qy 61 VEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDQAVSGLRSLTTLLRALGAQKEAIS 120
||||||||||||||||||||||||||||||||||||:|||||||||||||||||||||||
Db 61 VEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAIS 120
Qy 121 PPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR 166
||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR 166
WO2004022593 teaches a modified cytokine protein comprising the amino acid sequence of SEQ ID NO: 942, which is 99.1% identical to instant SEQ ID NO:1 (see the sequence alignment below).
ADL89608
(NOTE: this sequence has 6 duplicates in the database searched)
ID ADL89608 standard; protein; 166 AA.
XX
AC ADL89608;
XX
DT 03-JUN-2004 (first entry)
XX
DE Human modified cytokine protein #890.
XX
KW Human; cytokine; proteolysis; interferon; IFN; interleukin-10; IL-10;
KW long-chain cytokine family; short-chain cytokine family; infection;
KW allergy; heart disease; cancer; liver disorder; autoimmune disease;
KW growth disorder; diabetes; neurodegenerative disease; antimicrobial;
KW antiallergic; cytostatic; immunosuppressive; antidiabetic;
KW neuroprotective; mutant; mutein.
XX
OS Homo sapiens.
OS Synthetic.
XX
CC PN WO2004022593-A2.
XX
CC PD 18-MAR-2004.
XX
CC PF 08-SEP-2003; 2003WO-IB004347.
XX
PR 09-SEP-2002; 2002US-0409898P.
PR 21-MAR-2003; 2003US-0457135P.
XX
CC PA (NAUT-) NAUTILUS BIOTECH.
XX
CC PI Gantier R, Guyon T, Vega M, Drittanti L;
XX
DR WPI; 2004-248447/23.
XX
CC PT New modified cytokines with increased resistance to proteolysis, useful
CC PT for diagnosing and treating diseases such as infections, allergies, heart
CC PT diseases, cancer, liver disorders, autoimmune diseases or diabetes.
XX
CC PS Disclosure; SEQ ID NO 942; 316pp; English.
XX
CC The invention relates to modified cytokines that exhibit increased
CC resistance to proteolysis compared to unmodified cytokines. The invention
CC also relates to nucleic acid molecules encoding the cytokines, a
CC pharmaceutical composition comprising a nucleic acid molecule in a
CC pharmaceutical carrier, and a method of generating a protein or peptide
CC molecule having a predetermined property or activity, or a pre-selected
CC altered phenotype. The modified cytokine is selected from a member of the
CC interferons (IFNs)/interleukin (IL)-10 protein family, a member of the
CC long-chain cytokine family or a member of the short-chain cytokine
CC family. The composition and method are useful for diagnosing and treating
CC diseases such as infections, allergies, heart diseases, cancer, liver
CC disorders, autoimmune diseases, growth disorders, diabetes or
CC neurodegenerative diseases. This sequence represents a human modified
CC cytokine protein of the invention.
XX
SQ Sequence 166 AA;
Query Match 99.1%; Score 843; Length 166;
Best Local Similarity 98.8%;
Matches 164; Conservative 2; Mismatches 0; Indels 0; Gaps 0;
Qy 1 APPRLICDSRVLERYLLEAQEAENITTGCAEHCSLNENITVPDTQVNFYAWKRMEVGQQA 60
|||||||||||||||||||:||||||||||||||||||||||||||||||||||||||||
Db 1 APPRLICDSRVLERYLLEAKEAENITTGCAEHCSLNENITVPDTQVNFYAWKRMEVGQQA 60
Qy 61 VEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDQAVSGLRSLTTLLRALGAQKEAIS 120
||||||||||||||||||||||||||||||||||||:|||||||||||||||||||||||
Db 61 VEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAIS 120
Qy 121 PPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR 166
||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR 166
WO2009152944 teaches a human EPO mature protein mutant comprising the amino acid sequence of SEQ ID NO: 19, which is 99.1% identical to instant SEQ ID NO:1 (see the sequence alignment below).
SEQ ID NO:1
ID AXX71688 standard; protein; 166 AA.
XX
AC AXX71688;
XX
DT 10-JUN-2010 (first entry)
XX
DE Human erythropoietin (EPO) mature protein mutant, SEQ ID 19.
XX
KW Erythropoietin ligand; acquired immune deficiency syndrome; anemia;
KW antianemic; antiinflammatory; antisickling; cancer; chronic inflammation;
KW cytostatic; genetic-disease-gen.; hematological-gen.; hemorrhage;
KW hemostatic; immunostimulant; iron metabolism disorder; metabolic-gen.;
KW mutein; neurological disease; neuroprotective; protein therapy;
KW sickle cell anemia; thalassemia; therapeutic.
XX
OS Homo sapiens.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Misc-difference 20
FT /note= "Wild-type Lys substituted by Gln"
XX
CC PN WO2009152944-A1.
XX
CC PD 23-DEC-2009.
XX
CC PF 29-MAY-2009; 2009WO-EP003862.
XX
PR 29-MAY-2008; 2008US-0130376P.
XX
CC PA (HANA-) HANALL PHARM CO LTD.
XX
CC PI Borrelly G, Drittanti L, Gallet X, Guyon T, Vega M;
XX
DR WPI; 2009-S67343/08.
XX
CC PT New modified erythropoietin polypeptide, comprises two amino acid
CC PT modifications at masked is-Hit residues masked by different glycosylation
CC PT sites, useful for treating a disease or condition, e.g. anemias.
XX
CC PS Claim 10; SEQ ID NO 19; 279pp; English.
XX
CC The present invention relates to novel modified erythropoietin (EPO)
CC polypeptides that exhibit increased protease resistance and
CC pharmaceutical compositions comprising them. The modified erythropoietin
CC polypeptide, comprises two amino acid modifications at the masked is-Hit
CC residues which are masked by different glycosylation sites; and one or
CC more additional amino acid modifications at un-masked is-Hit residue. The
CC invention also provides a nucleic acid sequence encoding the modified EPO
CC polypeptide; a vector, comprising the nucleic acid sequence; a host cell,
CC comprising the vector; a pharmaceutical composition, comprising the
CC modified EPO polypeptide and a method for treating a disorder that is
CC amenable to treatment by EPO. The modified therapeutic polypeptide
CC contains one or more additional amino acid modifications that contributes
CC to altered immunogenicity, carboxylation, hydroxylation, carbamylation,
CC sulfation, phosphorylation, oxidation, PEGylation or protease resistance.
CC The modified EPO polypeptide, nucleic acid molecule, pharmaceutical
CC compositions and methods are useful for treating anemias that accompany
CC renal failure, AIDS, malignancy, chronic inflammation, perioperative
CC surgeries; iron overload disorder; abnormal hemostasis; tissue protective
CC therapy; neurological condition, thalassemia, sickle cell anemia, the
CC anemia of prematurity, anemia that accompanies cis-platinum chemotherapy,
CC and anemia following intensive radiotherapy, chemotherapy and bone marrow
CC transplantation. The recombinant EPO polypeptide has improved half-life
CC and useful as a biotherapeutic agent. The present sequence is a Human
CC erythropoietin (EPO) mature protein mutant that has improved half-life
CC and increase protease resistance.
XX
SQ Sequence 166 AA;
Query Match 99.1%; Score 843; Length 166;
Best Local Similarity 98.8%;
Matches 164; Conservative 2; Mismatches 0; Indels 0; Gaps 0;
Qy 1 APPRLICDSRVLERYLLEAQEAENITTGCAEHCSLNENITVPDTQVNFYAWKRMEVGQQA 60
||||||||||||||||||||||||||||||||||||||||||||:|||||||||||||||
Db 1 APPRLICDSRVLERYLLEAQEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQA 60
Qy 61 VEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDQAVSGLRSLTTLLRALGAQKEAIS 120
||||||||||||||||||||||||||||||||||||:|||||||||||||||||||||||
Db 61 VEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAIS 120
Qy 121 PPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR 166
||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR 166
US20080260820 teaches a human EPO mutein comprising the amino acid sequence of SEQ ID NO: 1529, which is 99.1% identical to instant SEQ ID NO:1 (see the sequence alignment below).
SEQ ID NO:1
ID ATS36124 standard; protein; 166 AA.
XX
AC ATS36124;
XX
DT 24-DEC-2008 (first entry)
XX
DE Human erythropoietin (EPO) mutein, SEQ ID 1529.
XX
KW protein therapy; therapeutic; viral infection; virucide; fibrosis;
KW antiinflammatory; condyloma; antimicrobial-gen.; dermatological; cancer;
KW cytostatic; growth disorder; growth-disorder-gen.;
KW acquired immune deficiency syndrome; immunostimulant; aging;
KW surgical procedure; surgical-gen.; congestive cardiomyopathy; cardiant;
KW liver transplantation; renal failure; nephrotropic; renal osteodystrophy;
KW osteoporosis; endocrine-gen.; osteopathic; achondroplasia; dysplasia;
KW inflammatory disease; Crohns disease; gastrointestinal-gen.;
KW immunosuppressive; short bowel syndrome; nutrition-disorder-gen.;
KW juvenile rheumatoid arthritis; antiarthritic; cystic fibrosis;
KW respiratory-gen.; male infertility; antiinfertility; uropathic; rickets;
KW osteopathic; down syndrome; nootropic; Spina bifida; neuroprotective;
KW genetic-disease-gen.; Noonan Syndrome; obesity; anorectic; fibromyalgia;
KW muscular-gen.; hepatitis c virus infection; hepatitis B virus infection;
KW hepatotropic; hairy cell leukemia; hematological-gen.; immunomodulator;
KW lymphoma; follicle center lymphoma; kaposis sarcoma; pulmonary fibrosis;
KW liver fibrosis; Turners syndrome; prader-willi syndrome; thalassemia;
KW erythropoietin; mutein.
XX
OS Homo sapiens.
OS Synthetic.
XX
CC PN US2008260820-A1.
XX
CC PD 23-OCT-2008.
XX
CC PF 19-APR-2007; 2007US-00788836.
XX
PR 19-APR-2007; 2007US-00788836.
XX
CC PA (BORR/) BORRELLY G.
CC PA (CHAU/) CHAUCHARD C.
CC PA (DRIT/) DRITTANTI L.
CC PA (VEGA/) VEGA M.
XX
CC PI Borrelly G, Chauchard C, Drittanti L, Vega M;
XX
DR WPI; 2008-M78313/75.
XX
CC PT New oral dosage formulation comprises a therapeutic polypeptide, tablet
CC PT or capsule, useful for treating a disease or condition, e.g. viral
CC PT infection, a fibrotic disorder, condylomata acuminate, cancer, and a
CC PT growth deficiency disorder.
XX
CC PS Claim 18; SEQ ID NO 1529; 120pp; English.
XX
CC The present invention relates to novel oral dosage formulations
CC comprising protease-resistant therapeutic peptides and their uses. In the
CC oral dosage formulation above, the therapeutic polypeptide contains one
CC or two amino acid sequence substitutions that render it more protease
CC resistant than in the absence of the modifications. The therapeutic
CC polypeptide is an interleukin (IL)-10, an interferon beta, an interferon
CC alpha, an interferon gamma, granulocyte colony stimulating leukemia
CC inhibitory factor, a growth hormone, ciliary neurotrophic factor, leptin,
CC insulin, oncostatin M, relaxin, IL-6, IL-12, erythropoietin, granulocyte-
CC macrophage colony stimulating factor, IL-2, IL-3, IL-4, IL-5, IL-13, F1t3
CC ligand, a monoclonal antibody or its fragment or a stem cell factor. The
CC invention also provides a tablet or capsule comprising 10-100 mg of an
CC interferon alpha (IFN-a), where the IFN-alpha is protease resistant by
CC virtue of its modifications and a method for treating a disease or
CC condition, comprising administering the oral dosage formulation of a
CC modified therapeutic polypeptide. The dosage formulation is useful for
CC treating viral infections, fibrotic disorders, condylomata acuminate,
CC cancer, growth deficiency disorders, AIDS, aging, impaired immune
CC function of HIV-infected subjects, catabolic illness, surgical recovery,
CC congestive cardiomyopathy, liver transplantation, liver regeneration
CC after hepatectomy, chronic renal failure, renal osteodystrophy,
CC osteoporosis, achondroplasia/hypochondroplasia, skeletal dysplasia,
CC chronic inflammatory disorder, Crohn's disease, short bowel syndrome,
CC juvenile chronic arthritis, cystic fibrosis, male infertility, X-linked
CC hypophosphatemic rickets, Down's syndrome, Spina bifida, Noonan Syndrome,
CC obesity, impaired muscle strength, fibromyalgia, hepatitis C infection,
CC hepatitis B infection, hairy cell leukemia, malignant lymphoma,
CC follicular lymphoma, AIDS-related Kaposi sarcoma, idiopathic pulmonary
CC fibrosis, liver fibrosis, renal fibrosis, Turner's syndrome, intrauterine
CC growth retardation, idiopathic short stature, Prader Willi syndrome, and
CC thalassemia. The present sequence is a Human erythropoietin (EPO) mutein,
CC used in the scope of the invention.
XX
SQ Sequence 166 AA;
4
ID AWO44428 standard; p
Query Match 99.1%; Score 843; Length 166;
Best Local Similarity 98.8%;
Matches 164; Conservative 2; Mismatches 0; Indels 0; Gaps 0;
Qy 1 APPRLICDSRVLERYLLEAQEAENITTGCAEHCSLNENITVPDTQVNFYAWKRMEVGQQA 60
||||||||||||||||||||||||||||||||||||||||||||:|||||||||||||||
Db 1 APPRLICDSRVLERYLLEAQEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQA 60
Qy 61 VEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDQAVSGLRSLTTLLRALGAQKEAIS 120
||||||||||||||||||||||||||||||||||||:|||||||||||||||||||||||
Db 61 VEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAIS 120
Qy 121 PPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR 166
||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR 166
KR2008094312 teaches a human EPO mutant polypeptide comprising the amino acid sequence of SEQ ID NO: 1529, which is 99.1% identical to instant SEQ ID NO:1 (see the sequence alignment below).
SEQ ID NO:1
ID AWO44428 standard; protein; 166 AA.
XX
AC AWO44428;
XX
DT 04-AUG-2022 (revised)
DT 23-JUL-2009 (first entry)
XX
DE Human EPO mutant polypeptide K20Q, SEQ ID 1529.
XX
KW protein therapy; therapeutic; prophylactic to disease;
KW metabolic disorder; metabolic-gen.; inflammatory disease;
KW antiinflammatory; autoimmune disease; immunosuppressive; viral infection;
KW virucide; antimicrobial-gen.; hematological disease; hematological-gen.;
KW heart disease; cardiant; neuropathy; neuroprotective;
KW gastrointestinal disease; gastrointestinal-gen.; cancer; cytostatic;
KW obesity; anorectic; nutrition-disorder-gen.; EPO; Erythropoietin ligand;
KW mutein.
XX
OS Homo sapiens.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Misc-difference 20
FT /note= "Wild-type Lys substituted by Gln"
XX
CC PN KR2008094312-A.
XX
CC PD 23-OCT-2008.
XX
CC PF 19-APR-2007; 2007KR-00038557.
XX
PR 19-APR-2007; 2007KR-00038557.
XX
CC PA (NAUT-) NAUTILUS BIOTECH.
XX
CC PI Borrelly G, Chauchard C, Drittanti L, Vega M;
XX
DR WPI; 2009-E78925/23.
XX
CC PT Oral dosage formulation for preventing and treating diseases e.g. cancer,
CC PT comprises therapeutic polypeptide having amino acid substitutions and
CC PT showing higher protease resistance than therapeutic polypeptide without
CC PT variation.
XX
CC PS Claim 18; SEQ ID NO 1529; 1901pp; Korean.
XX
CC The present invention relates to oral dosage formulations comprising
CC protease-resistant polypeptides. The present invention provides a method
CC for treating or preventing diseases by administering the oral dose
CC formulation. The present invention further provides refinement or
CC capsule, for e.g., enteric coated. In the invention, the polypeptides are
CC selected from interleukin-10 (IL-10), interferon-beta, interferon alpha,
CC interferon-gamma, granulocyte colony-stimulating factor (G-CSF), leukemia
CC inhibitory factor (LIF), growth hormone (GH), ciliary neurotrophic factor
CC (CNTF), leptin, insulin, oncostatin M, relaxin, interleukin-6 (IL-6),
CC interleukin-12 (IL-12), erythropoietin (EPO), granulocyte-macrophage
CC colony-stimulating factor (GM-CSF), interleukin-2 (IL-2), interleukin-3
CC (IL-3), interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-13 (IL-
CC 13), Flt3 ligand, monoclonal antibody or its fraction and stem cell
CC factor. The polypeptides used in the formulations comprise mutation in
CC the amino acid sequence when compared to its wild-type sequence. In the
CC invention, the diseases are selected from metabolic disease,
CC proliferative disease, inflammatory disease, autoimmune disease, viral
CC infection, microbism, blood disease, heart disease, neuropathy,
CC gastrointestinal disease, cancer, obesity, etc. The present sequence is a
CC human EPO mutant polypeptide used in the invention.
CC
CC Revised record issued on 04-AUG-2022 : Addition of DWPI-enhanced title
CC (PT field).
XX
SQ Sequence 166 AA;
Query Match 99.1%; Score 843; Length 166;
Best Local Similarity 98.8%;
Matches 164; Conservative 2; Mismatches 0; Indels 0; Gaps 0;
Qy 1 APPRLICDSRVLERYLLEAQEAENITTGCAEHCSLNENITVPDTQVNFYAWKRMEVGQQA 60
||||||||||||||||||||||||||||||||||||||||||||:|||||||||||||||
Db 1 APPRLICDSRVLERYLLEAQEAENITTGCAEHCSLNENITVPDTKVNFYAWKRMEVGQQA 60
Qy 61 VEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDQAVSGLRSLTTLLRALGAQKEAIS 120
||||||||||||||||||||||||||||||||||||:|||||||||||||||||||||||
Db 61 VEVWQGLALLSEAVLRGQALLVNSSQPWEPLQLHVDKAVSGLRSLTTLLRALGAQKEAIS 120
Qy 121 PPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR 166
||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PPDAASAAPLRTITADTFRKLFRVYSNFLRGKLKLYTGEACRTGDR 166
9. 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.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached Monday-Thursday, 7:00am-5:00pm EST.
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, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Chang-Yu Wang
October 5, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675
