DETAILED 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 .
Claim Status
Claims 1-21 are pending. Claims 18 and amended claims 20-21 are withdrawn as directed to an non-elected invention, namely methods. Claims 8 and 15-17 are withdrawn as directed to non-elected species. Claims 1-7, 9-14, and 19 are presently considered.
Election/Restrictions
Applicant’s election without traverse of Group I (original claims 1-17 and 19-21) in the reply filed on 11/26/2025 is acknowledged.
Applicant’s election of the species of SEQ ID NO: 106 in the reply filed on 11/26/2025 is acknowledged. Applicant did not state whether or not the election was made with traverse. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
The elected species is understood to be SEQ ID NO: 106, which has the following sequence:
HSQGTFTSDYSKYLDSQAAQDFVQWLLAGGPSSGAPPPSGGGGSGGGGSGGGGSADKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGAGGGGAGGGGAHPIPDSSPLLQFGGQVRQRYLYTDDAQQTEAHLEIREDGTVGGAADQSPESLLQLKALKPGVIQILGVKTSRFLCQRPDGALYGSLHFDPEACSFRERLLEDGYNVYQSEAHGLPLHCPGNKSPHRDPAPRGPCRFLPLPGLPPALPEPPGILAPQPPDVGSSDPLSMVGGSQGRSPSYES
Applicant identifies that this sequence has the arrangement of A-L1-F-L2-B, wherein “A” is a Glucagon analogue fragment, “F” is a long-acting protein unit fragment, “B” is an FGF21 analogue fragment, “L1” is a linker peptide fragment, and “L2” is a linker peptide fragment or absent (see, e.g., Reply filed 11/26/2025 at 8 at final ¶). Accordingly, within the elected species, “A” is understood to be
HSQGTFTSDYSKYLDSQAAQDFVQWLLAGGPSSGAPPPS
which reads upon instant claim 1 where X1 is H, X3 is Q, X16 is S, X17 is Q, X18 is A, X27 is L, X28 is A, X29 is absent, and Xz is SEQ ID NO: 2 (GGPSSGAPPPS), and wherein the entire “A” portion is disclosed on record as SEQ ID NO: 42 (see, e.g., instant claim 2). The originally elected species is understood to comprise an L1 of “GGGGSGGGGSGGGGSA” (i.e., instant SEQ ID NO: 14) and an “F” (long-acting protein unit fragment) of SEQ ID NO: 13:
DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGA
The originally claimed species is understood to have an L2 of GGGGAGGGGAGGGGA (SEQ ID NO: 18), and a “B” (FGF21 analogue fragment) is understood to be instant SEQ ID NO: 89:
HPIPDSSPLLQFGGQVRQRYLYTDDAQQTEAHLEIREDGTVGGAADQSPESLLQLKALKPGVIQILGVKTSRFLCQRPDGALYGSLHFDPEACSFRERLLEDGYNVYQSEAHGLPLHCPGNKSPHRDPAPRGPCRFLPLPGLPPALPEPPGILAPQPPDVGSSDPLSMVGGSQGRSPSYES
The originally elected species does not read upon instant claim 8 because SEQ ID NO: 106 does not comprise any of SEQ ID NOs: 56, 59, 60, 62, 65, 69, 70, or 71. Furthermore, the originally elected species does not read upon claims 15-17, because the elected species is a polypeptide rather than a polynucleotide (see, e.g., Requirement mailed 8/27/2025 at 2-4). Regarding claims 20-21, the originally elected group (i.e., Group I) is directed to products as identified in the Requirement mailed 11/26/2025 at page 3 and Footnote 1, but claims 20-21 were amended in the Reply filed 11/26/2025 to be directed to methods rather than products, wherein methods belong to a non-elected group; accordingly, claims 20-21 do not read upon Group I or the originally elected species. Accordingly, the originally elected species reads upon instant claim 1-7, 9-14, and 19.
Following extensive search and consideration, the originally elected species of SEQ ID NO: 106 has been deemed free of the prior art. Per MPEP § 803.02(III)
If the examiner determines that the elected species is allowable over the prior art, the examination of the Markush claim will be extended. If prior art is then found that anticipates or renders obvious the Markush claim with respect to a nonelected species, the Markush claim shall be rejected; claims to the nonelected species would still be held withdrawn from further consideration. The prior art search will not be extended unnecessarily to cover all nonelected species.
Accordingly, Examination was extended to the non-elected species of SEQ ID NOs: 91-115, which have all been deemed free of the prior art. The novelty arises in view of a combination of multiple mutations, including the consensus motif corresponding to instant SEQ ID NOs: 29, 32-33, 35, 38, and 42-44:
[HY]S[EQ]GTFTSDYSKYLD[ES][EQ]AAQDFVQWLL[AD]GGPSSGAPPPS
Wherein brackets show alternative residues at a single position. Accordingly, the subject matter at claims 2 and 14 are understood to be allowable over the prior art. Per MPEP § 803.02(III), examination has proceeded to non-elected species comprising the GLP-1 analogue of
[HY]S[EQ]GTFTSDYSKYLD[ES][EQS]AAQDFVQWLMAGPSSGAPPPS
conjugated as a multidomain fusion protein having a general structure of A-L1-B-L2-C, wherein A is a GLP-1analogue noted above, L1 is a first linker, B is a immunoglobulin Fc region, L2 is a second linker, and C is a fibroblast growth factor 21 (FGF21) or a variant thereof. Following extensive search and examination, the non-elected species was deemed anticipated and/or obvious in view of the prior art as applied below. Per MPEP § 803.02(III), claims directed to other nonelected species have been withdrawn.
Claims 18 and amended claims 20-21 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/26/2025.
Claims 8 and 15-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/26/2025.
Claims 1-7, 9-14, and 19 are presently considered
Priority
The priority claim to PCT/CN2020/070234, filed 1/03/2020, is acknowledged.
Examiner notes that no certified translation of the Foreign Application CN2019104074469 (filed 5/16/2019) has been placed on record. If applicant wants the application to be accorded benefit of the non-English language application, a certified translation is required (see 35 U.S.C. 119(b)(3), 37 CFR 1.55(g)(1)-(4)). Applicant is advised that any showing of priority that relies on a non-English language application is prima facie insufficient if no certified translation of the application is on file. See 37 CFR 41.154(b).
Information Disclosure Statement
The IDS filed 6/09/2022 and 04/09/2024 are acknowledged and presently considered.
The listing of references in the specification is not a proper information disclosure statement (see, e.g., Spec. filed 6/09/2022 at ¶¶[0003]-[0004],[0050]-[0051], [0089], [0092], [0096], [0102]). 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered. These references were known by the Applicant at the time of filing and are understood to be relevant and pertinent to the invention as evidenced by inclusion in the originally filed disclosure.
Claim Interpretation
The claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
Claim 1 is representative of the pending claim scope.
“Comprising” is an open-ended transitional term (see, e.g., MPEP § 2111.03(I)), wherein additional steps or components are not excluded. However, “‘[c]omprising’ is a term of art used in claim language which means that the named elements are essential” (see, e.g., id.; see also Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997)).
“Fusion protein” is undefined on record and therefore given its usual manner. The term is understood to include any polypeptide fused to another heterologous polypeptide in any manner, wherein the resulting polypeptide is suitable for recombinant expression.
A “Glucagon analogue fragment” is defined within the claims as any polypeptide that satisfies the requirements of SEQ ID NO: 81 as set forth at instant claims 1 and 19.
A “long-acting protein unit fragment” at claim 1 is undefined on record. Accordingly, the term is understood to broadly encompass any “protein unit fragment” (e.g., presumably carbon, hydrogen, oxygen, carbonyl moieties, etc.) identified in the art as “long-acting” or otherwise capable of improving the duration, length, or half-life of a protein (e.g., by reducing renal clearance or proteolytic degradation, etc.).
Claim 3 recites a product-by-process step, namely “is derived from” at line 2. Per MPEP § 2113(I),
"[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process."
In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985)
Accordingly, in the absence of clarification, claim 3 is understood to be fully satisfied by any “long-acting protein unit fragment” that may be “derived from” an Fc using any number of steps or reagents. This is reasonable because the resulting products are presumed to be structurally identical absent objective evidence to the contrary (see, e.g., MPEP § 2113(II), noting that the burden is on the Applicant to show product-by-process limitations result in a nonobvious difference).
Additional claim interpretations are set forth below.
Claim Rejections
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 3-7, 9-13, and 19 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites and requires “a long-acting protein unit fragment”, which renders the claim scope indefinite because the phrase, while exemplified (see, e.g., Spec. filed 6/09/2022 at ¶¶[0014]-[0015]), is not unambiguously defined on record. Therefore, the phrase “long-acting protein unit fragment” fails to correspond to an unambiguous and art-recognized definite having clear metes and bounds. Per MPEP § 2173, the primary purpose of 35 USC § 112(b) “is to ensure that the scope of the claims is clear so the public is informed of the boundaries of what constitutes infringement of the patent”; here, it is unknown what structures are included or excluded by the phrase at issue, and therefore the boundaries of what does or does not constitute infringement is not clear, and therefore claim 1 is rejected as indefinite. For purposes of applying prior art, the term is understood to broadly encompass any structure comprising one or more “protein unit fragment” (e.g., presumably carbon, hydrogen, oxygen, carbonyl moieties, etc.), wherein the structure is identified in the art as “long-acting” or otherwise capable of improving the duration, length, or half-life of a protein (e.g., by reducing renal clearance or proteolytic degradation, etc.). The phrase is understood to at least encompass the subgenera and structures set forth at dependent claims 3, 4, and SEQ ID NOs: 4-13.
Claim 4 recites “has a function of the polypeptide fragment defined in c)”, which renders the claim scope indefinite because the referenced “function” is not defined in the claim or on record. Peptides may have multiple “functions” (ubiquitination rate, degradation rate, receptor binding, renal clearance, Koff, Kon, “a function of improving the overall DPP-IV resistance”1, etc., etc.), but no specific function is recited within the claim. This is problematic because it is unknown which species (i.e., perhaps only a dozen, or perhaps trillions) share both (i) “at least 90% sequence identity with one of SEQ ID NO. 4-13” (>trillions’s of species), and also (ii) have “a function of the polypeptide fragment defined in c)” (see instant claim 4). Accordingly, in the absence of clarification of the specific “function” at issue, the “function” recited is a variable parameter that renders the claim scope indefinite2 (see, e.g., MPEP § 2173.05(b)(II), noting that a claim may be rendered indefinite when a limitation of the claim is defined by reference to an object and the relationship is not sufficiently defined; see also MPEP § 2173.05(g), noting that functional language that does not provide a “clear-cut indication of the scope of the subject matter embraced by the claim” is indefinite). For purposes of applying prior art, the functional parameter is deemed satisfied by all embodiments sharing at least 90% sequence identity to any one of SEQ ID NOs: 4-13. This is reasonable because such sequences would retain at least one or more functions of SEQ ID NOs: 4-13 (e.g., degradation rates, ability to bind, renal clearance, increased half-life due to hydrodynamic radius, etc., etc.).
Claim 5 recites “preferably”, which is exemplary language. Per MPEP § 2173.05(d), exemplary claim language identifying examples and preferences render a claim indefinite because it is unclear whether the preference is a limitation or optional. Here, in consideration of the claim scope in the context of the reduction to practice on record, it is unclear if the recitation is a required structural limitation or not, since all linkers of record appear to require such structure. Accordingly, claim 5 is rejected.
Claim 5 recites “first linker peptide fragment”, which refers to an undefined structure of unknown metes and bounds. It is unclear what structures constitute a “peptide fragment” and which do not. Specifically, it is unclear if “fragment” is limited to amino acids, dipeptides, tripeptides, etc., or if fragment includes carbon atoms, carbonyl moieties, etc.). Per MPEP § 2173, the primary purpose of 35 USC § 112(b) “is to ensure that the scope of the claims is clear so the public is informed of the boundaries of what constitutes infringement of the patent”; here, it is unknown what structures are included or excluded by the phrase at issue, and therefore the boundaries of what does or does not constitute infringement is not clear, and therefore claim 1 is rejected as indefinite. For purposes of applying prior art, the term is understood to broadly include any art-recognized linker comprising any fragment of any peptide (e.g., a carbon, carbonyl, etc.).
Claim 5 recites “rich in G, S and/or A”, and the term “rich” is a relative term that renders the claim indefinite. The term “rich” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear if “rich” requires a sequence to be 10%, 25%, 50%, 60%, 75%, 85%, 95%, 99%, or 100% Gly, Ser, and/or Ala. For purposes of applying prior art, “rich” is understood to be any sequence wherein Glycine, Ser, or Ala is represented, on average, more than other amino acids.
Claim 6 recites the phrase “a polypeptide fragment having an amino acid sequence shown in one of SEQ ID NOs: 14-23”. The verbiage utilized results in ambiguous claim scope because it is unclear if
(I) the “polypeptide fragment” must be “selected from the group consisting of SEQ ID NOs: 14-23” (i.e., it must be one of SEQ ID NOs: 14, 15, 16, 17, 18, 19, 20, 21, 22, or 23 is required to be present); or
(II) the “polypeptide fragment” may be “an amino acid sequence shown in one of SEQ ID NOs: 14-23” (i.e., any dipeptide subsequence present in any of SEQ ID NOs: 14-23) is included within the claim scope.
Applicant is advised that additional words and phrases are presumed to have meaning (see, e.g., Nystrom v. TREX Co., Inc., 424 F. 3d 1136, 1143 (Fed. Cir. 2005)), and therefore unnecessary verbiage should be avoided to minimize confusion. Accordingly, the metes and bounds of the claim scope is unclear, and therefore the claim is indefinite. For purposes of applying prior art, claim 6 is understood to read upon at least polypeptides comprising one of SEQ ID NOs: 14-23. Clarification is required.
Claim 9 recites “FGF21 analogue fragment” which is not defined on record and fails to correspond to an unambiguous art-recognized definition. Although exemplified on record (see, e.g., Spec. filed 6/09/2022 at ¶¶[0071]-[0074]), the term is not unambiguously defined on record. Therefore, the phrase “FGF21 analogue fragment” fails to correspond to an unambiguous and art-recognized definite having clear metes and bounds. Per MPEP § 2173, the primary purpose of 35 USC § 112(b) “is to ensure that the scope of the claims is clear so the public is informed of the boundaries of what constitutes infringement of the patent”; here, it is unknown what structures are included or excluded by the phrase at issue, and therefore the boundaries of what does or does not constitute infringement is not clear, and therefore claim 9 is rejected as indefinite. For purposes of applying prior art, the term is understood to broadly encompass any structure exemplified at instant claim 10 or otherwise exemplified in the Specification (see, e.g., Spec. filed 6/09/2022 at ¶¶[0071]-[0074]).
Claim 10 recites “wherein the FGF21 analogue fragment comprises ….an amino acid sequence shown in SEQ ID NO: 119” but subsequently states “wherein the N terminal HPIPDSS is missing or partially missing”, which renders the claim scope indefinite because the claim is internally inconsistent. It is unclear if the claimed FGF21 analogue either (i) “comprises e) a polypeptide fragment having an amino acid sequence shown in SEQ ID NO: 119” or (ii) does not actually comprise such a sequence because “the N terminal HPIPDSS is missing or partially missing”. For purposes of applying prior art, the claim is understood to mean “optionally the N terminal HPIPDSS is missing or partially missing”, such that the polypeptide fragment may comprise SEQ ID NO: 119.
Claim 10 recites “partially missing” which is relative terminology. The term “partially missing” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear if “partially missing” requires HPIPDSS to be missing one amino acid, two amino acids, three amino acids, four amino acids, five amino acid, or six amino acids. Furthermore, it is unclear if “partially missing” only includes truncations from the N-terminus, truncations from either the N- or C-termini, or if it may include N-terminal, C-terminal, and internal deletions (e.g., is HIDSS included or excluded?). Accordingly, claim 10 is rejected as indefinite. For purposes of applying prior art, the claim is understood to mean “optionally the N terminal HPIPDSS is missing or partially missing”, such that the polypeptide fragment may comprise SEQ ID NO: 119.
Claim 10 refers to “ a polypeptide fragment that has an amino acid sequence having at least 80% sequence identity with SEQ ID NO: 119”, but SEQ ID NO: 119 is a variable, non-unique sequence; therefore, it is unclear how identity is determined with respect to variable “X” residues. Sequence identity requires an exact match to constitute “identity”; therefore, a multivariable peptide of XXXXX shares 0% identity with AAAAA (this is consistent with BLAST alignments using X residues, wherein “X” only aligns with another “X”, but even then the sequences may be non-identical if the X’s are not identical). Similarly, SEQ ID NO: 119 is 181 amino acids in length, but contains 17 variable positions as shown at claim 10, and therefore it is unclear how the “at least 80% sequence identity” requirement should be applied to a variable sequence. For example,
The X residues may be deemed non-identities, meaning that the highest identity possible is 164/181 amino acids (90.6% sequence identity maximum). This would mean that only 19 additional amino acids from 181 could be varied, and the claim scope would presumably encompass ~1920-1 sequences;
The X residues may be deconvoluted into the definitions provided in all possible iterations (i.e., 17 variable positions, combinatorically representing 829,440 distinct, unique and fully defined sequences), and each such species of sequence is compared individually for sequences having “at least 80% sequence identity” with any one of the 829,440 different sequences, wherein “80%” represents 36 amino acids, implying a claim scope of >>trillions of sequences presumably encompassing >3620-1 species for each of 829,440 distinct sequences, minus overlapping identical structures;
Or perhaps another interpretation is intended. Accordingly, the reference of “at least 80%” sequence identity” relative to a variable sequence is indefinite because it is unclear how to account for the existing variable residues, and the Specification fails to provide guidance regarding how to perform and measure sequence identity with respect to a variable sequence. For purposes of applying prior art, at least any sequence sharing “80%” sequence identity with any FGF21 sequence at SEQ ID NOs: 87-90 using BLAST is deemed to satisfy the claim limitation of claim 10(f).
Claim 10 recites “has a function of the polypeptide fragment defined in e)”, which renders the claim scope indefinite because “function” is not defined in the claim or on record. Peptides may have multiple “functions” (ubiquitination rate, degradation rate, receptor binding, renal clearance, Koff, Kon, etc., etc.), and here the specification even identifies on regard that “FGF21” has “many functions”3, but no specific function is recited within the claim. This is problematic because it is unknown which species (i.e., perhaps only a dozen, or perhaps trillions) share both (i) “at least 80% sequence identity with SEQ ID NO. 119” (>trillions’s of species), and also (ii) have “a function of the polypeptide fragment defined in e)” (see instant claim 10). Accordingly, in the absence of clarification of the specific “function” at issue, the “function” recited is a variable parameter that renders the claim scope indefinite4 (see, e.g., MPEP § 2173.05(b)(II), noting that a claim may be rendered indefinite when a limitation of the claim is defined by reference to an object and the relationship is not sufficiently defined; see also MPEP § 2173.05(g), noting that functional language that does not provide a “clear-cut indication of the scope of the subject matter embraced by the claim” is indefinite). For purposes of applying prior art, any sequence sharing “80%” sequence identity with SEQ ID NO: 119 using BLAST and is identified as an FGF21 polypeptide is deemed to satisfy the claim limitation (i.e., the first possibility presented above).
Claim 10 recites “preferably”, which is exemplary language. Per MPEP § 2173.05(d), exemplary claim language identifying examples and preferences render a claim indefinite because it is unclear whether the preference is a limitation or optional. Here, in consideration of the claim scope in the context of the reduction to practice on record, it is unclear if the recitation is a required structural limitation or not, since exemplified embodiments of record appear to require such structure. Accordingly, claim 10 is rejected.
Claim 11 recites “preferably”, which is exemplary language. Per MPEP § 2173.05(d), exemplary claim language identifying examples and preferences render a claim indefinite because it is unclear whether the preference is a limitation or optional. Here, in consideration of the claim scope in the context of the reduction to practice on record, it is unclear if the recitation is a required structural limitation or not, since exemplified embodiments of record appear to require such structure. Accordingly, claim 11 is rejected.
Claim 11 recites “rich in G, S and/or A”, and the term “rich” is a relative term that renders the claim indefinite. The term “rich” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear if “rich” requires a sequence to be 10%, 25%, 50%, 60%, 75%, 85%, 95%, 99%, or 100% Gly, Ser, and/or Ala. For purposes of applying prior art, “rich” is understood to be any sequence wherein Glycine, Ser, or Ala is represented, on average, more than other amino acids.
Claim 12 recites “having an amino acid sequence shown in one of SEQ ID NO: 14-23”, which renders the claim scope indefinite because it is unclear if the claim includes or excludes subsequences within SEQ ID NOs: 14-23. The verbiage utilized results in ambiguous claim scope because it is unclear if
(I) the “polypeptide fragment” must be “selected from the group consisting of SEQ ID NOs: 14-23” (i.e., it must be one of SEQ ID NOs: 14, 15, 16, 17, 18, 19, 20, 21, 22, or 23 is required to be present); or
(II) the “polypeptide fragment” may be “an amino acid sequence shown in one of SEQ ID NOs: 14-23” (i.e., any dipeptide subsequence present in any of SEQ ID NOs: 14-23) is included within the claim scope.
Applicant is advised that additional words and phrases are presumed to have meaning (see, e.g., Nystrom v. TREX Co., Inc., 424 F. 3d 1136, 1143 (Fed. Cir. 2005)), and therefore unnecessary verbiage should be avoided to minimize confusion. Accordingly, the metes and bounds of the claim scope is unclear, and therefore the claim is indefinite. For purposes of applying prior art, claim 12 is understood to read upon at least polypeptides comprising one of SEQ ID NOs: 14-23. Clarification is required.
Claim 19 recites and refers to “a fusion protein or culture of the expression system according to claim 17”, but claim 17 does not recite fusion proteins, but is instead limited to polynucleotide-based expression systems. Accordingly, claim 19 is rejected for lack of antecedent basis, namely “a fusion protein . . . according to claim 17”. For purposes of applying prior art, the preamble of claim 19 is interpreted as “comprising a fusion protein
Claims 3-7, 9-13, and 19 depend directly or indirectly from one or more indefinite claims and fail to reconcile the indefiniteness of the claim(s) upon which they depend. Accordingly, these claims are rejected for the reasons applied to the claims upon which they depend.
Accordingly, claims 1, 3-7, 9-13, and 19 are rejected.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over US20170183383A1 (June 29, 2017).
Claim interpretation: The applicable claim interpretation has been set forth in preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding instant claims 1, 19, and the general variability of analogues of oxyntomodulin (OXM), glucagon-like peptide (GLP-1), Exenatide and glucagon, US’383 teaches and discloses analogues useful for preparing medication for treating hyperphagia, obesity and diabetes (see, e.g., US’383 at title, abs, claims). US’383 teaches and informs artisans that analogues include all species within the genus shown at claim 1 (see, e.g., US’383 at claim 1; see also US’383 at ¶¶[0010]-[0042], [0074]). Regarding instant claim 1, 19, and polypeptides having an amino acid sequence of instant SEQ ID NO: 81 as recited at claim 1, instant claim 1 recites and requires a sequence comprising SEQ ID NO: 81, or
X1SX3GTFTSDYSKYLDX16X17X18AQDFVQWLX27X28X29Xz
(see, e.g., instant claim 1 and SEQ ID NO: 81). The prior art teaches and discloses a substantially overlapping genus at claim 1 (compare instant claim 1 with US’383 at claim 1). US’383 satisfies the structural requirements of instant SEQ ID NO: 81 because it recites
HX2QGTFTSDX10SKX13LDX16X17X18AX20X21FX23X24WLX27X28X29X30X31X32X33X34X35X36X37X38X39X40
(see, e.g., US’383 at claim 1, see also US’383 at ¶¶[0010]-[0042], [0074]). US’383 overlaps in scope with instant claim 1, wherein positions are from the N- to C terminus, wherein X1 is H; X2 is S; X3 is Q; positions 4-9 are GTFTSD; X10 is Y; positions 11-12 are SK; X13 is Y; positions 14-15 are LD; X16 is S; X17 is K or R; X18 is A; position 19 is A; X20X21 is QD; position 22 is F; X23X24 is VQ; positions 25-26 are WL; X27 is Met or Leu; X28X29 is either D, A, DA, or DT since each position may be optionally absent; and positions corresponding to Xz and X30X31X32X33X34X35X36X37X38X39X40 are either GGPSSGAPPPS or GPSSGAPPPS (compare instant claim 1 with US’383 at claim 1, ¶¶[0010]-[0042], [0074]). Accordingly, the instant claims and US’383 read upon presumably equivalent proteins comprising a species selected from the genus of
HSQGTFTSDYSKYLDS[K or R]AAQDFVQWL[L or M][D,A,DA, or DT][GG or G]PSSGAPPPS
Accordingly, the instant claims substantially overlap in scope with the prior art genus of equivalent OXM analogues as taught and disclosed by US’383. Regarding instant claims 1, 19, and the requirement for “a long-acting protein unit fragment”, the phrase “long-acting protein unit” is not defined and has been rejected under 35 USC 112(b), above. For purposes of the instant rejection, it is noted that US’383 explicitly teaches a modification at position X17, wherein the analogue is conjugated to a lipophilic moiety (see, e.g., US’383 at claim 1-4, 7-11), which is identified as reducing renal clearance rate “thereby prolonging” the drug’s plasma half-life (see, e.g., US’383 at ¶¶[0009]). Regarding instant claim 19 and a pharmaceutical excipient, US’383 explicitly teaches that such compounds may be utilized in pharmaceutical compositions (see, e.g., US’383 at claims 8-11).
The primary reference differs from the pending claim scope as follows: Although US’383 describes and claims such embodiments, US’383 does not actually reduce to practice any species comprising sequences selected from the genus of
HSQGTFTSDYSKYLDS[K or R]AAQDFVQWL[L or M][D,A,DA, or DT][GG or G]PSSGAPPPS
Accordingly, the issue is whether or not such embodiments are obvious.
However, prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses, including non-exemplified embodiments (see, e.g., MPEP §§ 2123(I)-(II)). Accordingly, the OXM analogues taught and disclosed by the primary reference would be predicted and expected to act as OXM analogues by providing GCGR and GLP-1R dual agonist activity, and be usable in the applications described for such analogues, exactly as taught, disclosed, and suggested by the primary reference (see, e.g., US’383 at abs, claims 1, 8-11, discussing diabetes and obesity applications).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The claimed invention is the obvious combination of prior art elements according to known methods of forming OXM analogues, wherein such combination merely yields predicted and expected results, namely OXM analogues having improved half-life and suitable for use in the treatment of diabetes and obesity exactly as taught and disclosed by the primary reference (see, e.g., MPEP § 2143(I)(A), (D), (F), (G)). Furthermore, all elements merely perform the art-recognized function in combination as they do separately.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to make and utilize prior art structures within a prior art genus using routine biochemical techniques, wherein such embodiments would be understood to be equivalents for purposes of treating diabetes and obesity exactly as taught and suggested by the prior art.
Accordingly, claims 1 and 19 are rejected.
Claims 1, 3, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over US20140212440A1 (July 31, 2014).
Claim interpretation: The applicable claim interpretation has been set forth in preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding instant claims 1, 19, and a Glucagon analogue fragment comprising instant SEQ ID NO: 81, instant claim 1 recites and requires a sequence comprising SEQ ID NO: 81, or
X1SX3GTFTSDYSKYLDX16X17X18AQDFVQWLX27X28X29Xz
(see, e.g., instant claims 1, 22, 26, and SEQ ID NO: 81). US’440 teaches and discloses an overlapping genus of oxyntomodulin (OXM) conjugates, wherein the OXM has the structure of
R1-X1-X2-GTFTSD-X3-X4-X5-X6-X7-X8-X9-X10-X20-X21-X22-X23-X24-R2
(see, e.g., US’440 at claim 1 and 4). These two genera overlap where the US’440 sequence comprises an R1 of H or Y (i.e., corresponding to instant X1); an X1 of S; an X2 of either E or G (i.e., corresponding to instant X2); X3 is Y; X4 is S; X5 is K; X6 is Y; X7 is L; X8 is D; X9 is S or E (i.e., corresponding to instant X16); X10 is E, Q, or S (i.e., corresponding to instant X17); X11 is A, R, or V (i.e., corresponding to instant X17); X12 is A; X13 is Q; X14 is D; X15 is F; X16 is V; X17 is Q; X18 is W; X19 is L; X20 is M (i.e., corresponding to instant X27); X21 is deleted; X22 is alanine (i.e., corresponding to instant X28); X23 is deleted; X24 is deleted; and R2 is GPSSGAPPPS (i.e., corresponding to instant Xz). Accordingly, US’440 at claims 1 and 4 discloses at least functionally equivalent OXM analogues having the general structure of
[HY]S[EQ]GTFTSDYSKYLD[ES][EQS]AAQDFVQWLMAGPSSGAPPPS
This overlaps in scope with instant claims 1, 19, and SEQ ID NO: 81, wherein SEQ ID NO: 81 has the positions noted above, and additionally wherein X29 is absent and Xz is SEQ ID NO: 3 (GPSSGAPPPS). Accordingly, the “glucagon analogue fragment” of SEQ ID NO: 81 substantially and materially overlaps in scope with the prior art and known OXM analogues as taught and disclosed by US’440, and therefore such structures do not weight in favor of a determination of non-obviousness. Regarding instant claims 1, 3, 19, and a “long-acting protein unit fragment”, US’440 explicitly teaches and claims oxyntomodulin conjugates wherein the OXM is conjugated to an immunoglobulin Fc region via a non-peptidyl polymer (see, e.g., US’440 at claims 1, 3-4, 16, 19-21), and wherein the immunoglobulin is predicted and expected to improve half-life (see, e.g., US’440 at ¶¶[0007]-[0014]). Regarding the predicted and expected results of such compounds, US’440 identifies that such conjugates are predicted and expected to have known utility and applications, including anti-obesity effects (see, e.g., US’440 at claims 6, 22, and 26).
The primary reference differs from the pending claim scope as follows: Although US’440 describes and claims OXM conjugates having the general structure of
[HY]S[EQ]GTFTSDYSKYLD[ES][EQS]AAQDFVQWLMAGPSSGAPPPS-[Linker]-[Fc]
US’440 does not actually reduce to practice any species within this subgenus. Accordingly, the issue is whether or not such embodiments are obvious.
Prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses, including non-exemplified embodiments (see, e.g., MPEP §§ 2123(I)-(II)). Accordingly, the OXM analogues taught and disclosed by the primary reference would be predicted and expected to act as OXM analogues by providing GCGR and GLP-1R dual agonist activity, and be usable in the applications described for such analogues, exactly as taught, disclosed, and suggested by the primary reference (see, e.g., US’440 at abs, claims 1, 4, 6, 16-24 and 26, discussing obesity applications).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The claimed invention is the obvious combination of prior art elements according to known methods of forming OXM-Fc conjugates, wherein such combination merely yields predicted and expected results, namely OXM-Fc conjugates having improved half-life and suitable for use in the treatment of obesity exactly as taught and disclosed by the primary reference (see, e.g., MPEP § 2143(I)(A), (D), (F), (G)). Furthermore, all elements merely perform the art-recognized function in combination as they do separately.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to make and utilize prior art structures within a prior art genus using routine biochemical techniques, wherein such embodiments would be understood to be equivalents for purposes of treating obesity exactly as taught and suggested by the prior art.
Accordingly, claims 1, 3, and 19 are rejected.
Claims 1, 3-7, 9-13, and 19 are rejected under 35 U.S.C. 103 as being unpatentable over WO2018166461 (Sept. 20, 2018; corresponding to US Application No. 16/485,153) in view of US20140212440A1 (July 31, 2014).
Claim interpretation: The applicable claim interpretation has been set forth in preceding rejections and also in a separate section above, and those discussions and interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
Regarding instant claims 1, 3, 5-7, 9-13, 19, and the general structure of the claimed invention, WO’461 teaches and discloses fusion proteins having the general structure of A-L1-B-L2-C, wherein A is a GLP-1 agonist or analogue thereof, L1 is a first linker, B is a immunoglobulin Fc region, L2 is a second linker, and C is a fibroblast growth factor 21 (FGF21) or a variant thereof (see, e.g., WO’461 at claim 1). Accordingly, in view of WO’461, an artisan would readily appreciate that multi-domain proteins comprising a GLP-1 agonist (or analogue thereof) could be conjugated to an immunoglobulin Fc region, and also an FGF21 (or variant thereof). Accordingly, multidomain fusion proteins having the general structure of A-L1-B-L2-C were known in the prior art. Regarding instant claim 3 and a “long-acting protein unit fragment . . .derived from an Fc portion of mammalian immunoglobulin”, WO’461 explicitly teaches and discloses the use of an immunoglobulin Fc region, and specifically an IgG4 Fc (see, e.g., WO’461 at claim 1). Regarding instant claim 4 and a “long-acting protein unit fragment” sharing at least 90% sequence identity with any one of SEQ ID NOs: 4-13, WO’461 explicitly teaches and discloses the IgG4-Fc variant comprising SEQ ID NO: 11 (see, e.g., WO’461 at 21 at 2nd ¶), which shares 208/226 residues in common with instant SEQ ID NO: 13:
PNG
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227
676
media_image1.png
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Accordingly, the prior art teaches a compound sharing 208/226 residues, or >92% sequence identity with instant SEQ ID NO: 13, and such structure shares Fc functionality, and therefore is reasonably inferred to fully satisfy all limitations at instant claim 4(d). Regarding instant claims 5-6, 11-12, and a first and second linker comprising a sequence selected from instant SEQ ID NOs: 14-23, WO’461 explicitly teaches that the first and second linkers may be independently selected from GGGGSGGGGSGGGGS and GGGGSGGGGSGGGGSA (compare WO’461 at 13-14 at bridging ¶, claim 18 at page 35 with instant SEQ ID NOs: 13 and 14, respectively, showing 100% identity). Regarding instant claims 1, 5, 7, 11, 13, and the presence and order of each domain, WO’461 teaches, discloses, and reasonably directs artisans to make and use fusion proteins having the general structure of A-L1-B-L2-C, wherein A is a GLP-1 agonist or analogue thereof, L1 is a first linker, B is a immunoglobulin Fc region, L2 is a second linker, and C is a fibroblast growth factor 21 (FGF21) or a variant thereof (see, e.g., WO’461 at claim 1, page 17). Regarding instant claim 10 and an FGF21 analogue fragment sharing at least 80% sequence identity with instant SEQ ID NO: 119, claim 10 has been rejected as indefinite as explained above. For purposes of the instant rejection, claim 10(f) is understood to be satisfied if a prior art sequence shares at least 80% sequence identity with any of instant SEQ ID NOs: 87-90. Critically, the prior art teaches and discloses an FGF21 analogue, namely SEQ ID NO: 15 (see, e.g., WO’461 at 11 at 1st to final ¶¶), which shares 87% sequence identity with instant SEQ ID NO: 89, and the alignment is shown below:
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287
696
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Accordingly, the limitations of indefinite claim 10 do not reasonably appear to weigh in favor of a determination of non-obviousness. Regarding instant claim 19 and a pharmaceutical formulation, WO’461 explicitly teaches and claims pharmaceutical formulations (see, e.g., WO’461 at claims 1 and 24-28). Regarding predicted and expected utility, the disclosed multidomain fusion constructs of the prior art are predicted and expected to be useful in the treatment of metabolic diseases, including diabetes, obesity, and hepatic steatosis (see, e.g., WO’461 at abs, claims 24-28).
The primary reference differs from the instant claim scope as follows: WO’461 does not explicitly teach that GLP-1 analogue of A, within the prior art multidomain constructs of form A-L1-B-L2-C, may have a sequence selected from the genus of instant SEQ ID NO: 81 as required by instant claims 1 and 19.
WO’461 informs artisans that the multidomain fusion protein may comprise any “glucagon-like peptide-1(GLP-1) or an analogue thereof” (see, e.g., WO’461 at abs, claim 1). Accordingly, one of ordinary skill in the art would reasonably appreciate that any art-recognized GLP-1 analogue could be utilized to practice the claimed invention (see, e.g., WO’461 at abs, claim 1). An artisan would therefore reasonably review the prior art and identify art-recognized GLP-1 analogues5.
Notably, the prior art teaches and discloses GLP-1 analogues. Regarding GLP-1 analogues, US’440 teaches and discloses oxyntomodulin (OXM) analogues, which are understood to be alternatives to GLP-1 and capable of binding to the GLP-1 receptor (see, e.g., US’440 at ¶¶[0005]-[0008]), and having applications in the treatment of obesity (see, e.g., id. at claims). Accordingly, the OXM analogues taught and disclosed by US’440 would be readily understood to be GLP-1 analogues by one of ordinary skill in the art. Regarding instant claims 1, 19, and a Glucagon analogue fragment comprising instant SEQ ID NO: 81, instant claim 1 recites and requires a sequence comprising SEQ ID NO: 81, or
X1SX3GTFTSDYSKYLDX16X17X18AQDFVQWLX27X28X29Xz
(see, e.g., instant claims 1, 22, 26, and SEQ ID NO: 81). US’440 teaches and discloses an overlapping genus of oxyntomodulin (OXM) conjugates, wherein the OXM has the structure of
R1-X1-X2-GTFTSD-X3-X4-X5-X6-X7-X8-X9-X10-X20-X21-X22-X23-X24-R2
(see, e.g., US’440 at claim 1 and 4). These two genera overlap where the US’440 sequence comprises an R1 of H or Y (i.e., corresponding to instant X1); an X1 of S; an X2 of either E or G (i.e., corresponding to instant X2); X3 is Y; X4 is S; X5 is K; X6 is Y; X7 is L; X8 is D; X9 is S or E (i.e., corresponding to instant X16); X10 is E, Q, or S (i.e., corresponding to instant X17); X11 is A, R, or V (i.e., corresponding to instant X17); X12 is A; X13 is Q; X14 is D; X15 is F; X16 is V; X17 is Q; X18 is W; X19 is L; X20 is M (i.e., corresponding to instant X27); X21 is deleted; X22 is alanine (i.e., corresponding to instant X28); X23 is deleted; X24 is deleted; and R2 is GPSSGAPPPS (i.e., corresponding to instant Xz). Accordingly, US’440 at claims 1 and 4 discloses at least functionally equivalent OXM analogues having the general structure of
[HY]S[EQ]GTFTSDYSKYLD[ES][EQS]AAQDFVQWLMAGPSSGAPPPS
This overlaps in scope with instant claims 1, 19, and SEQ ID NO: 81, wherein SEQ ID NO: 81 has the positions noted above, and additionally wherein X29 is absent and Xz is SEQ ID NO: 3 (GPSSGAPPPS). Accordingly, the “glucagon analogue fragment” of SEQ ID NO: 81 substantially and materially overlaps in scope with the prior art and known OXM analogues as taught and disclosed by US’440, and therefore such structures do not weight in favor of a determination of non-obviousness.
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): First, the claimed invention is the obvious combination of prior art elements (i.e., the GLP-1 analogues of US’440, the Linkers of WO’461, the immunoglobulin Fc of WO’461, the FGF21 of WO’461) according to known methods of forming multidomain constructs of form A-L1-B-L2-C as taught and disclosed by the primary reference, wherein the resulting constructs would predictably and expectedly be useful in the treatment of diabetes and obesity exactly as taught and suggested in view of US’440 and WO’461 (see, e.g., MPEP § 2143(I)(A), (G)). Furthermore, all elements merely perform the art-recognized function in combination as they do separately. In addition, or alternatively, the claimed invention is obvious because it is the simple substitution of the GLP-1 analogues (“A”) of the primary reference within multidomain constructs of form A-L1-B-L2-C for other art-recognized GLP-1 analogues as taught by US’440, wherein such substitution would yield predicted and expected results, namely substituted multidomain constructs of form A-L1-B-L2-C suitable for use in the treatment of obesity and diabetes as taught and suggested in view of US’440 and WO’461 (see, e.g., MPEP § 2143(I)(B), (G)).
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to combine known prior art components in known arrangements using known and routine biochemical techniques, wherein such combination merely performs art-recognized benefits exactly as taught and suggested by the prior art.
Accordingly, claims 1, 3-7, 9-13, and 19 are rejected.
Allowable Subject Matter
Claims 2 and 14 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form. including all of the limitations of the base claim and any intervening claims. Examiner notes that all intervening structural limitations rendered moot in view of the explicitly recitations of sequence identifiers need not be repeated.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US8188040 discloses SEQ ID NO: 47, which appears to share substantial sequence identity with the Fc-Linker-FGF21 portion of instant SEQ ID NO: 106.
US9458214B2 discloses a dual function fusion protein comprising a GLP-1 receptor agonist, a FGF21 receptor agonist, and an Fc domain, attached to each other via a GS linker, and having an orientation of N-terminus-GLP-1 receptor agonist-linker-Fc domain-linker-FGF21 receptor agonist-C-terminus (see, e.g., US’214 at title, abs, claim 1).
US9731031B2 discloses oxyntomodulin conjugated to an immunoglobulin fragment (see, e.g., US’031 at title, abs, claims).
US 11858975 discloses and claims highly similar, but distinct species that are presently excluded from the pending claim scope (see, e.g., US’031 at title, abs, claims).
US20070237768A1 discloses FGF-21 compounds fused to specific IgG4-Fc or HSA derivatives resulting in fusion proteins that are biologically active with an extended elimination half-life and a slower clearance, and these FGF-21 compound fusion proteins and compositions are useful in treating type 2 diabetes, obesity, and metabolic syndrome (see, e.g., US’768 at title, abs, claims, passim).
US20140128318A1 discloses and claims novel oxyntomodulin derivatives and pharmaceutical composition for treating obesity comprising the same (see, e.g., US’318 at title, abs, claims).
US20150299282A1 discloses and claims a composition for preventing or treating diabetes, diabesity or diabetic complications, the composition comprising an oxyntomodulin analog as an active ingredient, wherein it is linked in a conjugate form to a half-life extending moiety (see, e.g., US’282 at title, abs, claims).
US20180311315A1 pertains to long-acting conjugates of GLP-1 agonists, and discloses conjugates of form X-La-F, wherein X is a peptide having activities to a glucagon receptor, L is a linker, and F is a material capable of increasing the half-life of X (see, e.g., US’315 at title, abs, claims, passim).
US20180305428A1 discloses long-acting fgf21 fusion proteins and pharmaceutical compositions comprising same (see, e.g., US’428 at title, abs, claims, passim).
WO2018081375A1 discloses Immunoglobulins and uses thereof, and generally teaches oxyntomodulin and other proteins conjugated to an Fc to increase half-life (see, e.g., id. at title, abs, claims, passim).
Pocai6 discusses the relationship and applications of both FGF21 and oxyntomodulin (see, e.g., id. at title, abs, passim).
Strohl7 discusses fusion proteins and strategies known in the art, circa 2015, for extending the half-life of protein therapeutics (see, e.g., id. at title, abs, passim).
Tschöp et al.8, discusses the trend towards unimolecular polypharmacy for treatment of diabetes and obesity, which is the process of taking different relative positions from various GLP-1 agonists and other similar proteins, and substituting those into a peptide to create a single molecule with dual activities (see, e.g., id. at title, abs, passim).
Yu et al.9 generally discusses fusion protein design, including multidomain fusion proteins, and the general state of the art circa 2014 (see, e.g., id. at title, abs, passim).
Conclusion
Claims 1, 3-7, 9-13, and 19 are rejected. Claims 2 and 14 are objected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
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, Lianko G. Garyu can be reached at (571) 270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/RANDALL L BEANE/ Primary Examiner, Art Unit 1654
1 See, e.g., Spec. filed 6/09/2022 at ¶[0068]).
2 See Datamize, LLC v. Plumtree Software, Inc., 417 F.3d 1342, 1350 (Fed. Cir. 2005) (“The scope of claim language cannot depend solely on the unrestrained, subjective opinion of a particular individual purportedly practicing the invention.”).
3 See, e.g., Spec. filed 6/09/2022 at ¶[0057]).
4 See Datamize, LLC v. Plumtree Software, Inc., 417 F.3d 1342, 1350 (Fed. Cir. 2005) (“The scope of claim language cannot depend solely on the unrestrained, subjective opinion of a particular individual purportedly practicing the invention.”).
5 The courts have previously noted that "[r]eading a list and selecting a known compound to meet known requirements is no more ingenious than selecting the last piece to put in the last opening in a jig-saw puzzle." (see, e.g., Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327 (1945), at 335).
6 Pocai, Action and therapeutic potential of oxyntomodulin. Mol Metab. 2013 Dec 14;3(3):241-51. doi: 10.1016/j.molmet.2013.12.001. PMID: 24749050; PMCID: PMC3986661; hereafter “Pocai”.
7 Strohl, W.R. Fusion Proteins for Half-Life Extension of Biologics as a Strategy to Make Biobetters. BioDrugs 29, 215–239 (2015). https://doi.org/10.1007/s40259-015-0133-6; hereafter “Strohl”.
8 Tschöp et al, Unimolecular Polypharmacy for Treatment of Diabetes and Obesity. Cell Metab. 2016 Jul 12;24(1):51-62. doi: 10.1016/j.cmet.2016.06.021. PMID: 27411008; hereafter “Tschop”.
9 Yu et al., Synthetic fusion protein design and applications. Biotechnol Adv. 2015 Jan-Feb;33(1):155-164. doi: 10.1016/j.biotechadv.2014.11.005. Epub 2014 Nov 18. PMID: 25450191; hereafter “Yu”.