DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendment and Arguments
2. Claims 1, 4, 22, 28 and 40-42 are pending.
Claims 31, drawn to a non-elected invention is not examined.
Claims 2, 3, 8, 9, 12-15, 18-20 and 35-39 have been cancelled.
Claims 40-42 have been added.
Claims 1, 4 and 22 have been amended.
Claims 1, 4, 22, 28 and 40-42 are examined on the merits.
3. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Withdrawn Grounds of Rejections
Claim Rejections - 35 USC § 112
4. The rejection of claim 22 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or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in light of the deletion of the table language and the addition of sequence identifying numbers, see Amendments to the Claims submitted June 2, 2026.
Claim Rejections - 35 USC § 102
5. The rejection of claim(s) 1, 4, 22 and 28 under 35 U.S.C. 102(a)(1) as being anticipated by Schellenberger et al., WO 2010/091122 A1 (published 12 August 2010) has been withdrawn in light of the amendment to claims 1, see Amendments to the Claims submitted June 2, 2026. Claims 2, 9 and 35 have been cancelled.
New Objection
Claim Objections
6. Claim 1 is objected to because of the following informality: the word, wherein is misspelled on the second line of the claim. The misspelled word, wherien should be deleted.
Correction is required.
New and Maintained Grounds of Rejection
Claim Rejections - 35 USC § 103
7. 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.
8. The rejection of claim(s) 1, 4, 22 and 28 and is/are rejected under 35 U.S.C. 103 as being unpatentable over Schellenberger et al., WO 2010/091122 A1 (published 12 August 2010) referenced herein as WOSchellenberger, and further in view of Schellenberger et al., US 2013/0165389 A1 (published June 27, 2013/ IDS reference A2 submitted November 26, 2025) referenced herein as USSchellenberger is maintained and made. Claims 2, 3, 8-15, 18-20 and 35-37 have been cancelled.
Applicant asserts “claim 1 recites a fusion protein with two subunits of an IL-12 or variants, fused to four extended recombinant polypeptides. Neither of the cited references, however, teach or suggest a fusion protein with four extended recombinant polypeptides. In particular, it is worth noting that in USSchellenberger, only an anti-IL-12 antibody is disclosed as part of the fusion proteins, not the IL-12 itself. Accordingly, USSchellenberger does not even contemplate a fusion protein that includes both extended recombinant polypeptides and an IL-12 with disulfide-linked subunits.”, see Remarks submitted June 2, 2026, page 5, 2nd paragraph (para.).
Applicant concludes arguments stating their teachings present surprising and unexpected results, wherein “in vivo experiments demonstrated that administration of the 4XTEN IL12 resulted in a significant decrease in tumor volume as compared to a control and the naked IL-12”, see para. bridging pages 5 and 6 of the Results.
Applicant’s arguments have been carefully considered, but fail to persuade.
WOSchellenberger teaches more than one XTEN unit can be used in a conjugate and/or composition, wherein a XTEN is linked to both the N-termini and C-termini, see page 27, section 00137; page 35, section 00155; and page 44, section 00171. XTENs are able to “…exhibit one or more of the following advantageous properties: conformational flexibility, enhanced aqueous solubility, high degree of protease resistance, low immunogenicity, low binding to mammalian receptors, and increased hydrodynamic (or Stokes) radii; properties that can make them particularly useful as fusion protein partners.”, see page 27, section 00137. Furthermore, “[n]on-limiting examples of the properties of the fusion proteins comprising [biologically active protein] BP that may be enhanced by XTEN include increases in the overall solubility and/or metabolic stability, reduced susceptibility to proteolysis, reduced immunogenicity, reduced rate of absorption when administered subcutaneously or intramuscularly, and enhanced pharmacokinetic properties such as terminal half-life and area under the curve (AUC), slower absorption after subcutaneous or intramuscular injection (compared to BP not linked to XTEN) such that the C.sub.m3x is lower, which may, in turn, result in reductions in adverse effects of the BP that, collectively, can result in an increased period of time that a fusion protein of a BPXTEN composition administered to a subject remains within a therapeutic window, compared to the corresponding BP component not linked to XTEN.”, see page 27, section 00138.
Likewise, USSchellenberger teaches more than one XTEN unit can be used, as well as the ability to select, link and manipulate XTENs to manufacture inventive compositions with advantageous properties, see page 18, sections 0132 and 0133; segments 3-5; Length of Sequence beginning on page 39; section 0188 spanning pages 44 and 45; and entire document.
Given both documents teach the availability and probability of utilizing more than one XTEN in a conjugate and/or composition, hence "where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235(CCPA 1955). Henceforth, it would not be unreasonable for one of ordinary skill in the art to arrive at the fusion protein claimed thereby rendering the same results Applicant assign to the claimed invention. There is no evidence presented that would negate the inability to manufacture the claimed fusion protein with the components and characteristics cited in the pending claims. Accordingly, the rejection is maintained.
WOSchellenberger a fusion protein comprising linkages between an extended recombinant polypeptide(s) (XTEN(s)), sequence motif with 12 amino acid residues a biologically active protein and a payload, see sections 0008-0010 on page 3; section 00125. “[T]he XTEN is characterized in that the sum of glycine (G), alanine (A), serine (S), threonine (T), glutamate (E) and proline (P) residues constitutes more than about…or about 90%, …of the total amino acid sequence of the XTEN,” and “…designed to be substantially non repetitive. In a preferred embodiment, XTEN sequences have predominately four to six types of amino acids selected from glycine (G), alanine (A), serine (S), threonine (T), glutamate (E) or proline (P) that are arranged in a substantially non-repetitive sequence that is greater than about 100 to about 3000 amino acid residues, preferably greater than 400 to about 3000 residues in length. In some embodiments, XTEN… the sequence consists of non-overlapping sequence motifs wherein each of the motifs has 9 to 36 amino acid residues wherein each of the motifs consists of 4 to 6 types of amino acids selected from glycine (G), alanine (A), serine (S), threonine (T), glutamate (E) and proline (P)”, see page 31, sections 00148 and 00149 spanning pages 31 and 32.
Biologically active proteins (BPs) XTEN are protein compositions that “…encompass fusion polypeptides that comprise one or two payload regions each comprising a biologically active protein that mediates one or more biological or therapeutic activities and at least one other region comprising at least one XTEN polypeptide.”, see page 44, section 00171.
“Examples of payloads include, but are not limited to, cytokines, enzymes, hormones and blood and growth factors. Payloads can further comprise genetically fused or chemically conjugated moieties such as chemotherapeutic agents, antiviral compounds, toxins, or contrast agents. These conjugated moieties can be joined to the rest of the polypeptide via a linker which may be cleavable or non-cleavable.”, see page 25, section 00126. The XTEN polypeptide may have multiple sites for proteolytic cleavage to release the XTEN, see page 16, sections 0079-0081; and page 44, section 00170. These sites are regarded by the Examiner as a release segment (RS) and capable of cleavage by a mammalian protease, see page 80, section 00260; and Table 10 on page 81.
“[T]he XTEN sequence consists of non-overlapping sequence motifs are from or more sequences…”, see page 4, lines 1 and 2; sections 00147- 00152 spanning pages 30-33. The sequence motifs that are the same as Applicant’s cited in claim 22 (SEQ ID NOs: 182-184 and 203), see sequence alignments.
WOSchellenberger teaches “…pharmaceutical compositions comprising the fusion protein of any of the foregoing embodiments and at least one pharmaceutically acceptable carrier.”, see page 8, section 0038.
The fusion proteins can be designed to have different configurations, N- to C-terminus, of a [biological active protein] BP, XTEN, an option spacer sequences.”, see page 8, section 0034.
WOSchellenberger does not teach the XTEN fusion polypeptide including a tumor targeting domain. WOSchellenberger does not teach the cytokine is IL-12, IL-12 p35 subunit or IL-12 p40 subunit.
However, USSchellenberger teaches a fusion protein comprising a tumor targeting moiety, a tumor-associated antigen (TAA), see page 15, section 0129; and Table 2 spanning pages 15-17.
USSchellenberger teaches cytokines, “biologically active IL-12 exists as a heterodimer comprised of 2 covalently linked subunits of 35 (p35) and 40 (p40) kD, the latter being known as IL-23. IL-12 is a cytokine that is an important part of the inflammatory response, and stimulates the production of interferon-gamma (IFN-g) and tumor necrosis factor-a (TNF-a) from T and natural killer (NK) cells, and reduces IL-4 mediated suppression of IFN-g.”, see page 50, sections 0227 and 0228.
It would have been obvious to one of ordinary skill in the art at the
effective filing date of the claimed invention was made to design a therapeutic fusion polypeptide comprising biologically active proteins, additional therapeutic agents including cytokines and cleavable release segments in an arrangement conducive for in vivo treatment and packaging in a pharmaceutical composition, see both documents in their entirety.
One of ordinary skill in the art would have been motivated to do so
with a reasonable expectation of success by teachings in both references, the different molecules arranged within the fusion protein there is different molecules conferring different activities and functions “…that can be useful for enhancing the biological, pharmaceutical, safety and/or therapeutic properties of biologically active proteins [as well as] for enhancing the pharmacokinetic properties, such as half-life, and increasing the time spent within the therapeutic window of a biologically active protein, see both documents in their entireties and in particular, Summary of the Invention beginning on page 2 of WOSchellenberger; and USSchellenberger, page 40, XTEN Segments beginning at section 0159. As also taught by WOSchellenberger,”[t]he choice of configuration can, …, confer particular pharmacokinetic, physico/chemical, or pharmacologic properties.”, see page 8, section 0034.
RESULT 1 from 182.align450.rag database.
AYG93335
ID AYG93335 standard; peptide; 12 AA.
XX
AC AYG93335;
XX
DT 30-SEP-2010 (first entry)
XX
DE XTEN sequence motif peptide SEQ ID 182.
XX
KW XTEN protein; acquired immune deficiency syndrome; anorectic;
KW antianginal; antiarthritic; antiinflammatory; cardiant;
KW cerebroprotective; coronary artery disease; crohns disease; cytostatic;
KW endocrine-gen.; extended recombinant polypeptide; factor ix deficiency;
KW factor vii deficiency; factor viii deficiency; gastrointestinal-gen.;
KW genetic-disease-gen.; glucagonoma; growth hormone deficiency;
KW growth-disorder-gen.; hypertension; hypotensive; immunostimulant;
KW immunosuppressive; ischemia; lipid metabolism disorder;
KW metabolic disorder; metabolic-gen.; multiple sclerosis;
KW muscular dystrophy; muscular-gen.; neuroprotective;
KW nutrition-disorder-gen.; ophthalmological; prader-willi syndrome;
KW protein therapy; recombinant protein; reperfusion injury;
KW retinal degeneration; rheumatoid arthritis; syndrome x; therapeutic;
KW turners syndrome; ulcerative colitis; vasotropic;
KW von willebrands disease; vulnerary.
XX
OS Unidentified.
XX
CC PN WO2010091122-A1.
XX
CC PD 12-AUG-2010.
XX
CC PF 03-FEB-2010; 2010WO-US023106.
XX
PR 03-FEB-2009; 2009US-0149669P.
PR 08-JUN-2009; 2009US-0185112P.
PR 08-JUN-2009; 2009US-0268193P.
PR 24-AUG-2009; 2009US-0236493P.
PR 25-AUG-2009; 2009US-0236836P.
PR 18-SEP-2009; 2009US-0243707P.
PR 24-SEP-2009; 2009US-0245490P.
PR 10-NOV-2009; 2009US-0280955P.
PR 10-NOV-2009; 2009US-0280956P.
PR 12-NOV-2009; 2009US-0281109P.
XX
CC PA (AMUN-) AMUNIX INC.
XX
CC PI Schellenberger V, Silverman J, Wang C, Spink B, Stemmer WP;
CC PI Geething N, To W, Cleland JL;
XX
DR WPI; 2010-K26088/55.
XX
CC PT New isolated extended recombinant polypeptide e.g. having non-repetitive
CC PT amino acid sequence, useful for treating a disease (e.g. obesity and
CC PT multiple sclerosis) and improving property (e.g. terminal half-life) of a
CC PT protein e.g. exendin-4.
XX
CC PS Claim 13; SEQ ID NO 182; 497pp; English.
XX
CC The present invention relates to a novel isolated extended recombinant
CC polypeptide (XTEN) e.g. having a non-repetitive amino acid sequence,
CC useful for treating a disease (e.g. obesity and multiple sclerosis) and
CC improving property (e.g. terminal half-life) of a protein e.g. exendin-4.
CC The invention also relates to compositions comprising extended
CC recombinant polypeptides (XTENs), isolated nucleic acids encoding the
CC compositions and vectors and host cells containing the same. XTENs are
CC generally extended length polypeptides with non-naturally occurring,
CC substantially non-repetitive sequences that are composed mainly of small
CC hydrophilic amino acids, with the sequence having a low degree or no
CC secondary or tertiary structure under physiologic conditions. XTEN
CC polypeptide compositions are useful as fusion partners that can be linked
CC to biologically active proteins (BPs), resulting in a BPXTEN fusion
CC proteins (e.g., monomeric fusions). XTENs can have utility as fusion
CC protein partners in that they can confer certain chemical and
CC pharmaceutical properties when linked to a biologically active protein to
CC a create a fusion protein. The novel composition is useful for: treating
CC glucose-related diseases, metabolic diseases, coagulation disorders, and
CC growth hormone-related disorders and conditions, such as type I or type
CC II diabetes, obesity, hyperglycemia, hyperinsulinemia, abnormal insulin
CC production, insulin resistance, syndrome X, excessive appetite,
CC insufficient satiety, glucagonoma, dyslipidemia, retinal
CC neurodegenerative processes, factor VII deficiency, factor X deficiency,
CC factor XII deficiency, hemophilia A, hemophilia B, Von Willebrand
CC disease, hypertension, acute coronary syndrome, rheumatoid arthritis,
CC reperfusion injury following ischemia, growth-hormone deficiency,
CC Turner's Syndrome, Prader-Willi Syndrome, idiopathic short stature, AIDS
CC wasting, multiple sclerosis, Crohn's disease, ulcerative colitis or
CC muscular dystrophy; and improving a property of a protein. The present
CC sequence represents a polypeptide sequence which was useful during the
CC invention as a component of a BPXTEN fusion protein.
XX
SQ Sequence 12 AA;
Query Match 100.0%; Score 61; Length 12;
Best Local Similarity 100.0%;
Matches 12; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GESPGGSSGSES 12
||||||||||||
Db 1 GESPGGSSGSES 12
RESULT 1 from 183.align450.rag database.
AYG93336
ID AYG93336 standard; peptide; 12 AA.
XX
AC AYG93336;
XX
DT 30-SEP-2010 (first entry)
XX
DE XTEN sequence motif peptide SEQ ID 183.
XX
KW XTEN protein; acquired immune deficiency syndrome; anorectic;
XX
OS Unidentified.
XX
CC PN WO2010091122-A1.
XX
CC PD 12-AUG-2010.
XX
CC PF 03-FEB-2010; 2010WO-US023106.
XX
CC PA (AMUN-) AMUNIX INC.
XX
CC PI Schellenberger V, Silverman J, Wang C, Spink B, Stemmer WP;
CC PI Geething N, To W, Cleland JL;
XX
DR WPI; 2010-K26088/55.
XX
CC PT New isolated extended recombinant polypeptide e.g. having non-repetitive
CC PT amino acid sequence, useful for treating a disease (e.g. obesity and
CC PT multiple sclerosis) and improving property (e.g. terminal half-life) of a
CC PT protein e.g. exendin-4.
XX
CC PS Claim 13; SEQ ID NO 183; 497pp; English.
XX
CC The present invention relates to a novel isolated extended recombinant
CC polypeptide (XTEN) e.g. having a non-repetitive amino acid sequence,
CC useful for treating a disease (e.g. obesity and multiple sclerosis) and
CC improving property (e.g. terminal half-life) of a protein e.g. exendin-4.
CC The invention also relates to compositions comprising extended
CC recombinant polypeptides (XTENs), isolated nucleic acids encoding the
CC compositions and vectors and host cells containing the same. XTENs are
CC generally extended length polypeptides with non-naturally occurring,
CC substantially non-repetitive sequences that are composed mainly of small
CC hydrophilic amino acids, with the sequence having a low degree or no
CC secondary or tertiary structure under physiologic conditions. XTEN
CC polypeptide compositions are useful as fusion partners that can be linked
CC to biologically active proteins (BPs), resulting in a BPXTEN fusion
CC proteins (e.g., monomeric fusions). XTENs can have utility as fusion
CC protein partners in that they can confer certain chemical and
CC pharmaceutical properties when linked to a biologically active protein to
CC a create a fusion protein. The novel composition is useful for: treating
CC glucose-related diseases, metabolic diseases, coagulation disorders, and
CC growth hormone-related disorders and conditions, such as type I or type
CC II diabetes, obesity, hyperglycemia, hyperinsulinemia, abnormal insulin
CC production, insulin resistance, syndrome X, excessive appetite,
CC insufficient satiety, glucagonoma, dyslipidemia, retinal
CC neurodegenerative processes, factor VII deficiency, factor X deficiency,
CC factor XII deficiency, hemophilia A, hemophilia B, Von Willebrand
CC disease, hypertension, acute coronary syndrome, rheumatoid arthritis,
CC reperfusion injury following ischemia, growth-hormone deficiency,
CC Turner's Syndrome, Prader-Willi Syndrome, idiopathic short stature, AIDS
CC wasting, multiple sclerosis, Crohn's disease, ulcerative colitis or
CC muscular dystrophy; and improving a property of a protein. The present
CC sequence represents a polypeptide sequence which was useful during the
CC invention as a component of a BPXTEN fusion protein.
XX
SQ Sequence 12 AA;
Query Match 100.0%; Score 61; Length 12;
Best Local Similarity 100.0%;
Matches 12; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GSEGSSGPGESS 12
||||||||||||
Db 1 GSEGSSGPGESS 12
RESULT 1 from 184.align450.rag database.
AYG93337
(NOTE: this sequence has 61 duplicates in the database searched.
See complete list at the end of this report)
ID AYG93337 standard; peptide; 12 AA.
XX
AC AYG93337;
XX
DT 30-SEP-2010 (first entry)
XX
DE XTEN sequence motif peptide SEQ ID 184.
XX
KW XTEN protein; acquired immune deficiency syndrome; anorectic;
KW antianginal; antiarthritic; antiinflammatory; cardiant;
KW cerebroprotective; coronary artery disease; crohns disease; cytostatic;
KW endocrine-gen.; extended recombinant polypeptide; factor ix deficiency;
KW factor vii deficiency; factor viii deficiency; gastrointestinal-gen.;
KW genetic-disease-gen.; glucagonoma; growth hormone deficiency;
KW growth-disorder-gen.; hypertension; hypotensive; immunostimulant;
KW immunosuppressive; ischemia; lipid metabolism disorder;
KW metabolic disorder; metabolic-gen.; multiple sclerosis;
KW muscular dystrophy; muscular-gen.; neuroprotective;
KW nutrition-disorder-gen.; ophthalmological; prader-willi syndrome;
KW protein therapy; recombinant protein; reperfusion injury;
KW retinal degeneration; rheumatoid arthritis; syndrome x; therapeutic;
KW turners syndrome; ulcerative colitis; vasotropic;
KW von willebrands disease; vulnerary.
XX
OS Unidentified.
XX
CC PN WO2010091122-A1.
XX
CC PD 12-AUG-2010.
XX
CC PF 03-FEB-2010; 2010WO-US023106.
XX
CC PA (AMUN-) AMUNIX INC.
XX
CC PI Schellenberger V, Silverman J, Wang C, Spink B, Stemmer WP;
CC PI Geething N, To W, Cleland JL;
XX
DR WPI; 2010-K26088/55.
XX
CC PT New isolated extended recombinant polypeptide e.g. having non-repetitive
CC PT amino acid sequence, useful for treating a disease (e.g. obesity and
CC PT multiple sclerosis) and improving property (e.g. terminal half-life) of a
CC PT protein e.g. exendin-4.
XX
CC PS Claim 13; SEQ ID NO 184; 497pp; English.
XX
CC The present invention relates to a novel isolated extended recombinant
CC polypeptide (XTEN) e.g. having a non-repetitive amino acid sequence,
CC useful for treating a disease (e.g. obesity and multiple sclerosis) and
CC improving property (e.g. terminal half-life) of a protein e.g. exendin-4.
CC The invention also relates to compositions comprising extended
CC recombinant polypeptides (XTENs), isolated nucleic acids encoding the
CC compositions and vectors and host cells containing the same. XTENs are
CC generally extended length polypeptides with non-naturally occurring,
CC substantially non-repetitive sequences that are composed mainly of small
CC hydrophilic amino acids, with the sequence having a low degree or no
CC secondary or tertiary structure under physiologic conditions. XTEN
CC polypeptide compositions are useful as fusion partners that can be linked
CC to biologically active proteins (BPs), resulting in a BPXTEN fusion
CC proteins (e.g., monomeric fusions). XTENs can have utility as fusion
CC protein partners in that they can confer certain chemical and
CC pharmaceutical properties when linked to a biologically active protein to
CC a create a fusion protein. The novel composition is useful for: treating
CC glucose-related diseases, metabolic diseases, coagulation disorders, and
CC growth hormone-related disorders and conditions, such as type I or type
CC II diabetes, obesity, hyperglycemia, hyperinsulinemia, abnormal insulin
CC production, insulin resistance, syndrome X, excessive appetite,
CC insufficient satiety, glucagonoma, dyslipidemia, retinal
CC neurodegenerative processes, factor VII deficiency, factor X deficiency,
CC factor XII deficiency, hemophilia A, hemophilia B, Von Willebrand
CC disease, hypertension, acute coronary syndrome, rheumatoid arthritis,
CC reperfusion injury following ischemia, growth-hormone deficiency,
CC Turner's Syndrome, Prader-Willi Syndrome, idiopathic short stature, AIDS
CC wasting, multiple sclerosis, Crohn's disease, ulcerative colitis or
CC muscular dystrophy; and improving a property of a protein. The present
CC sequence represents a polypeptide sequence which was useful during the
CC invention as a component of a BPXTEN fusion protein.
XX
SQ Sequence 12 AA;
Query Match 100.0%; Score 61; Length 12;
Best Local Similarity 100.0%;
Matches 12; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GSSESGSSEGGP 12
||||||||||||
Db 1 GSSESGSSEGGP 12
RESULT 1 from 203.align450.rag database.
AYG93356
ID AYG93356 standard; peptide; 12 AA.
XX
AC AYG93356;
XX
DT 30-SEP-2010 (first entry)
XX
DE XTEN sequence motif peptide SEQ ID 203.
XX
KW XTEN protein; acquired immune deficiency syndrome; anorectic;
KW antianginal; antiarthritic; antiinflammatory; cardiant;
KW cerebroprotective; coronary artery disease; crohns disease; cytostatic;
KW endocrine-gen.; extended recombinant polypeptide; factor ix deficiency;
KW factor vii deficiency; factor viii deficiency; gastrointestinal-gen.;
KW genetic-disease-gen.; glucagonoma; growth hormone deficiency;
KW growth-disorder-gen.; hypertension; hypotensive; immunostimulant;
KW immunosuppressive; ischemia; lipid metabolism disorder;
KW metabolic disorder; metabolic-gen.; multiple sclerosis;
KW muscular dystrophy; muscular-gen.; neuroprotective;
KW nutrition-disorder-gen.; ophthalmological; prader-willi syndrome;
KW protein therapy; recombinant protein; reperfusion injury;
KW retinal degeneration; rheumatoid arthritis; syndrome x; therapeutic;
KW turners syndrome; ulcerative colitis; vasotropic;
KW von willebrands disease; vulnerary.
XX
OS Unidentified.
XX
CC PN WO2010091122-A1.
XX
CC PD 12-AUG-2010.
XX
CC PF 03-FEB-2010; 2010WO-US023106.
XX
CC PA (AMUN-) AMUNIX INC.
XX
CC PI Schellenberger V, Silverman J, Wang C, Spink B, Stemmer WP;
CC PI Geething N, To W, Cleland JL;
XX
DR WPI; 2010-K26088/55.
XX
CC PT New isolated extended recombinant polypeptide e.g. having non-repetitive
CC PT amino acid sequence, useful for treating a disease (e.g. obesity and
CC PT multiple sclerosis) and improving property (e.g. terminal half-life) of a
CC PT protein e.g. exendin-4.
XX
CC PS Claim 13; SEQ ID NO 203; 497pp; English.
XX
CC The present invention relates to a novel isolated extended recombinant
CC polypeptide (XTEN) e.g. having a non-repetitive amino acid sequence,
CC useful for treating a disease (e.g. obesity and multiple sclerosis) and
CC improving property (e.g. terminal half-life) of a protein e.g. exendin-4.
CC The invention also relates to compositions comprising extended
CC recombinant polypeptides (XTENs), isolated nucleic acids encoding the
CC compositions and vectors and host cells containing the same. XTENs are
CC generally extended length polypeptides with non-naturally occurring,
CC substantially non-repetitive sequences that are composed mainly of small
CC hydrophilic amino acids, with the sequence having a low degree or no
CC secondary or tertiary structure under physiologic conditions. XTEN
CC polypeptide compositions are useful as fusion partners that can be linked
CC to biologically active proteins (BPs), resulting in a BPXTEN fusion
CC proteins (e.g., monomeric fusions). XTENs can have utility as fusion
CC protein partners in that they can confer certain chemical and
CC pharmaceutical properties when linked to a biologically active protein to
CC a create a fusion protein. The novel composition is useful for: treating
CC glucose-related diseases, metabolic diseases, coagulation disorders, and
CC growth hormone-related disorders and conditions, such as type I or type
CC II diabetes, obesity, hyperglycemia, hyperinsulinemia, abnormal insulin
CC production, insulin resistance, syndrome X, excessive appetite,
CC insufficient satiety, glucagonoma, dyslipidemia, retinal
CC neurodegenerative processes, factor VII deficiency, factor X deficiency,
CC factor XII deficiency, hemophilia A, hemophilia B, Von Willebrand
CC disease, hypertension, acute coronary syndrome, rheumatoid arthritis,
CC reperfusion injury following ischemia, growth-hormone deficiency,
CC Turner's Syndrome, Prader-Willi Syndrome, idiopathic short stature, AIDS
CC wasting, multiple sclerosis, Crohn's disease, ulcerative colitis or
CC muscular dystrophy; and improving a property of a protein. The present
CC sequence represents a polypeptide sequence which was useful during the
CC invention as a component of a BPXTEN fusion protein.
SQ Sequence 12 AA;
Query Match 100.0%; Score 62; Length 12;
Best Local Similarity 100.0%;
Matches 12; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GSPSEPTEGTSA 12
||||||||||||
Db 1 GSPSEPTEGTSA 12
9. Claim(s) 1, 4, 22, 28 and 40-42 is/are rejected under 35 U.S.C. 103 as being unpatentable over Schellenberger et al., WO 2010/091122 A1 (published 12 August 2010) referenced herein as WOSchellenberger, and further in view of Schellenberger et al., US 2013/0165389 A1 (published June 27, 2013/ IDS reference A2 submitted November 26, 2025) referenced herein as USSchellenberger, Ho et al., WO 2014/182532 A1 (published 13 November 2014) and Yang et al., WO 2019126576 A1 (published 27 June 2019).
WOSchellenberger teaches more than one XTEN unit can be used in a conjugate and/or composition, wherein a XTEN is linked to both the N-termini and C-termini, see page 27, section 00137; page 35, section 00155; and page 44, section 00171. XTENs are able to “…exhibit one or more of the following advantageous properties: conformational flexibility, enhanced aqueous solubility, high degree of protease resistance, low immunogenicity, low binding to mammalian receptors, and increased hydrodynamic (or Stokes) radii; properties that can make them particularly useful as fusion protein partners.”, see page 27, section 00137. Furthermore, “[n]on-limiting examples of the properties of the fusion proteins comprising [biologically active protein] BP that may be enhanced by XTEN include increases in the overall solubility and/or metabolic stability, reduced susceptibility to proteolysis, reduced immunogenicity, reduced rate of absorption when administered subcutaneously or intramuscularly, and enhanced pharmacokinetic properties such as terminal half-life and area under the curve (AUC), slower absorption after subcutaneous or intramuscular injection (compared to BP not linked to XTEN) such that the C.sub.m3x is lower, which may, in turn, result in reductions in adverse effects of the BP that, collectively, can result in an increased period of time that a fusion protein of a BPXTEN composition administered to a subject remains within a therapeutic window, compared to the corresponding BP component not linked to XTEN.”, see page 27, section 00138.
WOSchellenberger a fusion protein comprising linkages between an extended recombinant polypeptide(s) (XTEN(s)), sequence motif with 12 amino acid residues a biologically active protein and a payload, see sections 0008-0010 on page 3; section 00125. “[T]he XTEN is characterized in that the sum of glycine (G), alanine (A), serine (S), threonine (T), glutamate (E) and proline (P) residues constitutes more than about…or about 90%, …of the total amino acid sequence of the XTEN,” and “…designed to be substantially non repetitive. In a preferred embodiment, XTEN sequences have predominately four to six types of amino acids selected from glycine (G), alanine (A), serine (S), threonine (T), glutamate (E) or proline (P) that are arranged in a substantially non-repetitive sequence that is greater than about 100 to about 3000 amino acid residues, preferably greater than 400 to about 3000 residues in length. In some embodiments, XTEN… the sequence consists of non-overlapping sequence motifs wherein each of the motifs has 9 to 36 amino acid residues wherein each of the motifs consists of 4 to 6 types of amino acids selected from glycine (G), alanine (A), serine (S), threonine (T), glutamate (E) and proline (P)”, see page 31, sections 00148 and 00149 spanning pages 31 and 32.
Biologically active proteins (BPs) XTEN are protein compositions that “…encompass fusion polypeptides that comprise one or two payload regions each comprising a biologically active protein that mediates one or more biological or therapeutic activities and at least one other region comprising at least one XTEN polypeptide.”, see page 44, section 00171.
“Examples of payloads include, but are not limited to, cytokines, enzymes, hormones and blood and growth factors. Payloads can further comprise genetically fused or chemically conjugated moieties such as chemotherapeutic agents, antiviral compounds, toxins, or contrast agents. These conjugated moieties can be joined to the rest of the polypeptide via a linker which may be cleavable or non-cleavable.”, see page 25, section 00126. The XTEN polypeptide may have multiple sites for proteolytic cleavage to release the XTEN, see page 16, sections 0079-0081; and page 44, section 00170. These sites are regarded by the Examiner as a release segment (RS) and capable of cleavage by a mammalian protease, see page 80, section 00260; and Table 10 on page 81.
“[T]he XTEN sequence consists of non-overlapping sequence motifs are from or more sequences…”, see page 4, lines 1 and 2; sections 00147- 00152 spanning pages 30-33. The sequence motifs that are the same as Applicant’s cited in claim 22 (SEQ ID NOs: 182-184 and 203), see sequence alignments in first cited 103 rejection.
WOSchellenberger teaches “…pharmaceutical compositions comprising the fusion protein of any of the foregoing embodiments and at least one pharmaceutically acceptable carrier.”, see page 8, section 0038.
The fusion proteins can be designed to have different configurations, N- to C-terminus, of a [biological active protein] BP, XTEN, an option spacer sequences.”, see page 8, section 0034.
WOSchellenberger does not teach the XTEN fusion polypeptide including a tumor targeting domain. WOSchellenberger does not teach the cytokine is IL-12, IL-12 p35 subunit or IL-12 p40 subunit, as well as each RS shares at least 88% sequence identity to Applicant’s SEQ ID Nos: 337 and 376.
However, USSchellenberger teaches a fusion protein comprising a tumor targeting moiety, a tumor-associated antigen (TAA), see page 15, section 0129; and Table 2 spanning pages 15-17. Moreover, USSchellenberger teaches cytokines, “biologically active IL-12 exists as a heterodimer comprised of 2 covalently linked subunits of 35 (p35) and 40 (p40) kD, the latter being known as IL-23. IL-12 is a cytokine that is an important part of the inflammatory response, and stimulates the production of interferon-gamma (IFN-g) and tumor necrosis factor-a (TNF-a) from T and natural killer (NK) cells, and reduces IL-4 mediated suppression of IFN-g.”, see page 50, sections 0227 and 0228.
USSchellenberger teaches more than one XTEN unit can be used, as well as the ability to select, link and manipulate XTENs to manufacture inventive compositions with advantageous properties, see page 18, sections 0132 and 0133; segments 3-5; Length of Sequence beginning on page 39; section 0188 spanning pages 44 and 45; and entire document.
Furthermore, Ho teaches components of a conjugate including the IL 12 p40 subunit (sequence 10) that is the same as Applicant’s SEQ ID NO: 5, see sequence alignment at end of rejection. Ho also teaches the IL 12 p35 subunit (sequence 8) that is the same as Applicant’s SEQ ID NO: 6, see sequence alignment at end of rejection.
Yang teaches RS that are 100% sequence identical to SEQ ID NOs: 337 and 376 and within activatable recombinant polypeptide, see sequence alignments. “In some instances, the activatable recombinant polypeptide compositions include an XTEN linked to binding moieties by cleavable release segments that, when cleaved, the binding moieties are capable of binding together effector T cells with targeted tumor or cancer cells and effecting cytolysis of the tumor cells or cancer cells.”, see abstract; and entire document.
It would have been obvious to one of ordinary skill in the art at the
effective filing date of the claimed invention was made to design a therapeutic fusion polypeptide comprising biologically active proteins, additional therapeutic agents including cytokines and cleavable RS in an arrangement conducive for in vivo treatment and packaging in a pharmaceutical composition, see all documents in their entirety.
One of ordinary skill in the art would have been motivated to do so
with a reasonable expectation of success by teachings in all references, the different molecules arranged within the fusion protein conferring different activities and functions “…that can be useful for enhancing the biological, pharmaceutical, safety and/or therapeutic properties of biologically active proteins [as well as] for enhancing the pharmacokinetic properties, such as half- life, and increasing the time spent within the therapeutic window of a biologically active protein, see all documents in their entireties and in particular, Summary of the Invention beginning on page 2 of WOSchellenberger; and USSchellenberger, page 40, XTEN Segments beginning at section 0159. As also taught by the references,”[t]he choice of configuration can, …, confer particular pharmacokinetic, physico/chemical, or pharmacologic properties” with the RS providing ability to direct rates of cleavage and access to tumor-associated proteases able to facilitate in vivo treatment of tumor or surrounding tissue, see WOSchellenberger, page 8, section 0034; Yang, page 4, section 4; page 13, section 0016; page 33, section 0127; and entirety of all documents.
BBP98681 from 5.rag database.
ID BBP98681 standard; protein; 335 AA.
DT 01-JAN-2015 (first entry)
XX
DE Mouse IL 12 p40 subunit, SEQ 10.
XX
KW IL12; Interleukin 12 ligand; breast tumor; cancer; cholangiocarcinoma;
KW cytostatic; dermatological; endocrine-gen.; gastrointestinal-gen.;
KW gynecological; immunoconjugate; lung tumor; mesothelioma; metastasis;
KW ovary tumor; pancreas tumor; prostate tumor; respiratory-gen.;
KW squamous cell carcinoma; stomach tumor; therapeutic; tumor suppressor;
KW uropathic.
XX
OS Mus musculus.
XX
CC PN WO2014182532-A1.
XX
CC PD 13-NOV-2014.
XX
CC PF 01-MAY-2014; 2014WO-US036296.
XX
PR 07-MAY-2013; 2013US-0820543P.
XX
CC PA (USSH ) US DEPT HEALTH & HUMAN SERVICES.
XX
CC PI Ho M, Pastan IH, Kim H;
XX
DR WPI; 2014-U39579/78.
DR N-PSDB; BBP98680.
XX
CC PT New conjugate comprising interleukin-12 subunits p35 and p40 linked to a
CC PT mesothelin-specific antibody comprising a variable heavy domain and
CC PT variable light domain, useful for treating a subject having mesothelin-
CC PT expressing cancer.
XX
CC PS Disclosure; SEQ ID NO 10; 54pp; English.
XX
CC The present invention relates to a novel conjugate comprising an
CC interleukin-12 (IL 12) subunits p35 and p40 linked to a mesothelin-
CC specific antibody, useful for treating mesothelin-expressing cancer. The
CC invention further provides: a composition comprising a therapeutically
CC effective amount of the conjugate; a method for inhibiting tumor growth
CC or metastasis in a subject; and a method for treating mesothelin-
CC expressing cancer selected from mesothelioma, prostate cancer, lung
CC cancer, stomach cancer, squamous cell carcinoma, pancreatic cancer,
CC cholangiocarcinoma, triple negative breast cancer or ovarian cancer. The
CC present sequence represents a nucleotide sequence of a mouse IL 12
CC subunits p40, which is linked to the novel conjugate and used for
CC treating mesothelin-expressing cancer.
XX
SQ Sequence 335 AA;
Query Match 100.0%; Score 1694; DB 1; Length 335;
Best Local Similarity 100.0%;
Matches 313; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MWELEKDVYVVEVDWTPDAPGETVNLTCDTPEEDDITWTSDQRHGVIGSGKTLTITVKEF 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 23 MWELEKDVYVVEVDWTPDAPGETVNLTCDTPEEDDITWTSDQRHGVIGSGKTLTITVKEF 82
Qy 61 LDAGQYTCHKGGETLSHSHLLLHKKENGIWSTEILKNFKNKTFLKCEAPNYSGRFTCSWL 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 83 LDAGQYTCHKGGETLSHSHLLLHKKENGIWSTEILKNFKNKTFLKCEAPNYSGRFTCSWL 142
Qy 121 VQRNMDLKFNIKSSSSSPDSRAVTCGMASLSAEKVTLDQRDYEKYSVSCQEDVTCPTAEE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 143 VQRNMDLKFNIKSSSSSPDSRAVTCGMASLSAEKVTLDQRDYEKYSVSCQEDVTCPTAEE 202
Qy 181 TLPIELALEARQQNKYENYSTSFFIRDIIKPDPPKNLQMKPLKNSQVEVSWEYPDSWSTP 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 203 TLPIELALEARQQNKYENYSTSFFIRDIIKPDPPKNLQMKPLKNSQVEVSWEYPDSWSTP 262
Qy 241 HSYFSLKFFVRIQRKKEKMKETEEGCNQKGAFLVEKTSTEVQCKGGNVCVQAQDRYYNSS 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 263 HSYFSLKFFVRIQRKKEKMKETEEGCNQKGAFLVEKTSTEVQCKGGNVCVQAQDRYYNSS 322
Qy 301 CSKWACVPCRVRS 313
|||||||||||||
Db 323 CSKWACVPCRVRS 335
Search completed: August 13, 2026, 22:09:29
Job time : 1 secs
RESULT 1 from 6.rag database.
BBP98679
DT 01-JAN-2015 (first entry)
XX
DE Mouse IL 12 p35 subunit, SEQ 8.
XX
KW IL12; Interleukin 12 ligand; breast tumor; cancer; cholangiocarcinoma;
KW cytostatic; dermatological; endocrine-gen.; gastrointestinal-gen.;
KW gynecological; immunoconjugate; lung tumor; mesothelioma; metastasis;
KW ovary tumor; pancreas tumor; prostate tumor; respiratory-gen.;
KW squamous cell carcinoma; stomach tumor; therapeutic; tumor suppressor;
KW uropathic.
XX
OS Mus musculus.
XX
CC PN WO2014182532-A1.
XX
CC PD 13-NOV-2014.
XX
CC PF 01-MAY-2014; 2014WO-US036296.
XX
PR 07-MAY-2013; 2013US-0820543P.
XX
CC PA (USSH ) US DEPT HEALTH & HUMAN SERVICES.
XX
CC PI Ho M, Pastan IH, Kim H;
XX
DR WPI; 2014-U39579/78.
DR N-PSDB; BBP98678.
XX
CC PT New conjugate comprising interleukin-12 subunits p35 and p40 linked to a
CC PT mesothelin-specific antibody comprising a variable heavy domain and
CC PT variable light domain, useful for treating a subject having mesothelin-
CC PT expressing cancer.
XX
CC PS Disclosure; SEQ ID NO 8; 54pp; English.
XX
CC The present invention relates to a novel conjugate comprising an
CC interleukin-12 (IL 12) subunits p35 and p40 linked to a mesothelin-
CC specific antibody, useful for treating mesothelin-expressing cancer. The
CC invention further provides: a composition comprising a therapeutically
CC effective amount of the conjugate; a method for inhibiting tumor growth
CC or metastasis in a subject; and a method for treating mesothelin-
CC expressing cancer selected from mesothelioma, prostate cancer, lung
CC cancer, stomach cancer, squamous cell carcinoma, pancreatic cancer,
CC cholangiocarcinoma, triple negative breast cancer or ovarian cancer. The
CC present sequence represents a nucleotide sequence of a mouse IL 12
CC subunits p35, which is linked to the novel conjugate and used for
CC treating mesothelin-expressing cancer.
XX
SQ Sequence 193 AA;
Query Match 100.0%; Score 998; Length 193;
Best Local Similarity 100.0%;
Matches 193; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RVIPVSGPARCLSQSRNLLKTTDDMVKTAREKLKHYSCTAEDIDHEDITRDQTSTLKTCL 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 RVIPVSGPARCLSQSRNLLKTTDDMVKTAREKLKHYSCTAEDIDHEDITRDQTSTLKTCL 60
Qy 61 PLELHKNESCLATRETSSTTRGSCLPPQKTSLMMTLCLGSIYEDLKMYQTEFQAINAALQ 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PLELHKNESCLATRETSSTTRGSCLPPQKTSLMMTLCLGSIYEDLKMYQTEFQAINAALQ 120
Qy 121 NHNHQQIILDKGMLVAIDELMQSLNHNGETLRQKPPVGEADPYRVKMKLCILLHAFSTRV 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 NHNHQQIILDKGMLVAIDELMQSLNHNGETLRQKPPVGEADPYRVKMKLCILLHAFSTRV 180
Qy 181 VTINRVMGYLSSA 193
|||||||||||||
Db 181 VTINRVMGYLSSA 193
RESULT 1 from 337.rag database.
BGL91246
(NOTE: this sequence has 8 duplicates in the database searched.
See complete list at the end of this report)
ID BGL91246 standard; peptide; 29 AA.
XX
AC BGL91246;
XX
DT 08-AUG-2019 (first entry)
XX
DE Legumain/MMP2/7/9/11/14/uPA/matriptase substrate RSN-0003, SEQ 132.
XX
KW Legumain; MMP11 protein; MMP14 protien; MMP2 protein; MMP7 protein;
KW MMP9 protein; MT1-MMP; Matrilysin 1; Matriptase; Metalloprotease-11;
KW Metalloprotease-14; Metalloprotease-2; Metalloprotease-7;
KW Metalloprotease-9; andrology; cytostatic; dermatological;
KW dermatological disease; endocrine disease; endocrine-gen.;
KW gastrointestinal disease; gastrointestinal-gen.; gelatinase A;
KW gelatinase B; genitourinary disease; gynecological;
KW gynecology and obstetrics; hematological disease; hematological-gen.;
KW immune disorder; immunomodulator; matrix metalloproteinase- 11;
KW matrix metalloproteinase-14; matrix metalloproteinase-2;
KW matrix metalloproteinase-7; matrix metalloproteinase-9;
KW musculoskeletal disease; musculoskeletal-gen.; neoplasm;
KW neurological disease; neuroprotective; protein production;
KW protein therapy; recombinant protein; respiratory disease;
KW respiratory-gen.; stromelysin 3; substrate; therapeutic; uPA; urokinase;
KW uropathic.
XX
OS Unidentified.
XX
CC PN WO2019126576-A1.
XX
CC PD 27-JUN-2019.
XX
CC PF 20-DEC-2018; 2018WO-US066939.
XX
PR 21-DEC-2017; 2017US-0609296P.
PR 17-DEC-2018; 2018US-0780719P.
XX
CC PA (AMUN-) AMUNIX PHARM INC.
XX
CC PI Yang F, Schellenberger V, Podust V, Sim B, Thayer D, Beaber J;
XX
DR WPI; 2019-53991Q/51.
XX
CC PT Recombinant polypeptide comprises first release segment (RS1), where RS1
CC PT is a substrate for cleavage by mammalian protease.
XX
CC PS Claim 3; SEQ ID NO 132; 385pp; English.
XX
CC The present invention relates to a novel recombinant polypeptide, useful
CC for treating a disease in a subject. The recombinant polypeptide
CC comprises a first release segment (RS1), where RS1 corresponds to SEQ ID
CC NO's: 1-619 (see BGL91115-BGL91733) is a substrate for cleavage by a
CC mammalian protease. The invention further relates to: (1) a method for
CC treating a disease in a subject, which involves administering one or more
CC therapeutically effective doses of the recombinant polypeptide or a
CC pharmaceutical composition comprising the recombinant polypeptide to the
CC subject in need; (2) a kit, which comprises the pharmaceutical
CC composition, a container and a label or package insert on or associated
CC with the container; (3) an isolated nucleic acid, which comprises a
CC polynucleotide encoding the recombinant polypeptide or complement of the
CC polynucleotide; (4) an expression vector, which comprises polynucleotide
CC sequence and a recombinant regulatory sequence operably linked to the
CC polynucleotide sequence; (5) an isolated host cell, which comprises
CC expression vector; (6) a recombinant polypeptide; (7) a pharmaceutical
CC composition, which comprises recombinant polypeptide and one or more
CC pharmaceutically suitable excipients; and (8) a method for manufacturing
CC an activatable recombinant polypeptide composition. The disease includes
CC hematological disease, gastrointestinal disease, andrology, neoplasm,
CC dermatological disease, endocrine disease, genitourinary disease, immune
CC disorder, gynecology and obstetrics, respiratory disease, musculoskeletal
CC disease and neurological disease.
XX
SQ Sequence 29 AA;
Query Match 100.0%; Score 149; Length 29;
Best Local Similarity 100.0%;
Matches 29; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GSAPGAEGGYAALRMGGEIATSGSETPGT 29
|||||||||||||||||||||||||||||
Db 1 GSAPGAEGGYAALRMGGEIATSGSETPGT 29
RESULT 1 from 376.align450_DX.rag database.
BGL91285
ID BGL91285 standard; peptide; 29 AA.
XX
AC BGL91285;
XX
DT 08-AUG-2019 (first entry)
XX
DE Legumain/MMP2/7/9/11/14/uPA/matriptase substrate RSN-0042, SEQ 171.
XX
KW Legumain; MMP11 protein; MMP14 protien; MMP2 protein; MMP7 protein;
KW MMP9 protein; MT1-MMP; Matrilysin 1; Matriptase; Metalloprotease-11;
KW Metalloprotease-14; Metalloprotease-2; Metalloprotease-7;
KW Metalloprotease-9; andrology; cytostatic; dermatological;
KW dermatological disease; endocrine disease; endocrine-gen.;
KW gastrointestinal disease; gastrointestinal-gen.; gelatinase A;
KW gelatinase B; genitourinary disease; gynecological;
KW gynecology and obstetrics; hematological disease; hematological-gen.;
KW immune disorder; immunomodulator; matrix metalloproteinase- 11;
KW matrix metalloproteinase-14; matrix metalloproteinase-2;
KW matrix metalloproteinase-7; matrix metalloproteinase-9;
KW musculoskeletal disease; musculoskeletal-gen.; neoplasm;
KW neurological disease; neuroprotective; protein production;
KW protein therapy; recombinant protein; respiratory disease;
KW respiratory-gen.; stromelysin 3; substrate; therapeutic; uPA; urokinase;
KW uropathic.
XX
OS Unidentified.
XX
CC PN WO2019126576-A1.
XX
CC PD 27-JUN-2019.
XX
CC PF 20-DEC-2018; 2018WO-US066939.
XX
PR 21-DEC-2017; 2017US-0609296P.
PR 17-DEC-2018; 2018US-0780719P.
XX
CC PA (AMUN-) AMUNIX PHARM INC.
XX
CC PI Yang F, Schellenberger V, Podust V, Sim B, Thayer D, Beaber J;
XX
DR WPI; 2019-53991Q/51.
XX
CC PT Recombinant polypeptide comprises first release segment (RS1), where RS1
CC PT is a substrate for cleavage by mammalian protease.
XX
CC PS Claim 3; SEQ ID NO 171; 385pp; English.
XX
CC The present invention relates to a novel recombinant polypeptide, useful
CC for treating a disease in a subject. The recombinant polypeptide
CC comprises a first release segment (RS1), where RS1 corresponds to SEQ ID
CC NO's: 1-619 (see BGL91115-BGL91733) is a substrate for cleavage by a
CC mammalian protease. The invention further relates to: (1) a method for
CC treating a disease in a subject, which involves administering one or more
CC therapeutically effective doses of the recombinant polypeptide or a
CC pharmaceutical composition comprising the recombinant polypeptide to the
CC subject in need; (2) a kit, which comprises the pharmaceutical
CC composition, a container and a label or package insert on or associated
CC with the container; (3) an isolated nucleic acid, which comprises a
CC polynucleotide encoding the recombinant polypeptide or complement of the
CC polynucleotide; (4) an expression vector, which comprises polynucleotide
CC sequence and a recombinant regulatory sequence operably linked to the
CC polynucleotide sequence; (5) an isolated host cell, which comprises
CC expression vector; (6) a recombinant polypeptide; (7) a pharmaceutical
CC composition, which comprises recombinant polypeptide and one or more
CC pharmaceutically suitable excipients; and (8) a method for manufacturing
CC an activatable recombinant polypeptide composition. The disease includes
CC hematological disease, gastrointestinal disease, andrology, neoplasm,
CC dermatological disease, endocrine disease, genitourinary disease, immune
CC disorder, gynecology and obstetrics, respiratory disease, musculoskeletal
CC disease and neurological disease.
XX
SQ Sequence 29 AA;
Query Match 100.0%; Score 154; Length 29;
Best Local Similarity 100.0%;
Matches 29; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GSAPGPGGGYAELAMGGTRATSGSETPGT 29
|||||||||||||||||||||||||||||
Db 1 GSAPGPGGGYAELAMGGTRATSGSETPGT 29
Conclusion
10. 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.
11. Any inquiry concerning this communication or earlier communications from the Examiner should be directed to ALANA HARRIS DENT whose telephone number is (571)272-0831. The Examiner works a flexible schedule, however she can generally be reached 8AM-8PM, Monday through Friday.
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, Julie Wu can be reached at 571-272-5205. 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.
ALANA HARRIS DENT
Primary Examiner
Art Unit 1643
20 July 2026
/Alana Harris Dent/Primary Examiner, Art Unit 1643
Prosecution Insights