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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 5/23/2025 has been entered.
Claim Status
Claims 41-45 and 47-61 are pending.
Claim 41 is currently amended.
Claims 1-40 and 46 are cancelled.
Claims 52-60 are withdrawn as being directed to a non-elected method invention.
Claim 44 is rejoined.
Claims 41-45, 47-51, and 61 have been examined.
Priority
This application is a CON of 16/933,908 07/20/2020 PAT 11725033
16/933,908 is a CON of PCT/US2019/014363 01/18/2019
PCT/US2019/014363 has PRO 62/654,303 04/06/2018
PCT/US2019/014363 has PRO 62/619,683 01/19/2018
Withdrawn Rejection
The rejection of claims 41-42, 45, and 47-50 on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 6-8 of U.S. Patent No. 11,725,033 is withdrawn because the amendment to claim 41 overcomes the rejection. However, the claims are subject to new ground of rejection.
New Ground of Objection and Rejection
Claim Objections
Claim 41 is objected to because of the following informalities:
Claim 41 contains the acronym “GDF11”, and an acronym in the first instance of claims should be expanded upon/spelled out as “growth differentiation factor 11” with the acronym indicated in parentheses as (GDF11). The abbreviations can be used thereafter.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 41-45, 47-51, and 61 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a NEW MATTER rejection..
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Claim 41 adds a limitation of a single tryptophan (W) attached to the end of the C-terminus of the native GDF11 protein via a single amino acid without support by the specification of record. Although the specification of Fig. 13A disclosed a peptide sequence of SEQ ID NO: 20 shown as follows, the disclosed peptide sequence of SEQ ID NO: 20 does not support the New MATTER limitation of a single tryptophan (W) attached to the end of the C-terminus of the native GDF11 protein via a single amino acid. Because the tryptophan residue is no longer directly linked to the C-terminus of the native GDF11 shown in SEQ ID NO: 20), claim 41 is rejected as NEW MATTER without support by the specification of record. Claims 42-43, 45, 47-51, and 61 are rejected as depending on claim 41.
Modified Rejection
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 41-45, 47-51, and 61 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention for the reasons as follows.
The specification failed to provide a representative number of a GFD11 variant comprising [a native GDF11 protein]-(a linking amino acid)1-(Tryptophan2-(Any amino acid)3-6 as claimed.
The specification defined "variant" referred to a polypeptide substantially homologous to a native or reference polypeptide comprising one or a plurality of deletions, insertions or substitutions [0067]. The specification further disclosed a GDFl1 variant further comprising alternative amino acids of natural or non-natural amin acids [0073]. However, a single disclosed peptide SEQ ID NO: 20 comprising a native human GDF11 protein with additional dipeptide of
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WE shown as follows does not represent the entire genus of a modified GDF11 variant comprising a native GDF11 protein across various species (e.g., monkey, dog, pig, and other mammals). Furthermore, the native GDF11 protein fusion to another peptide (X1-Trp)-X0-4 with unknown sequence length but comprising a tryptophan linked to the C-terminus of the native GDF11 protein via an linking amino acid as claimed. The specification fails to satisfy the written description requirement because (a) the disclosed native human GDF11 protein does not represent the entire genus a native GDF11 protein across numerous mammal species as claimed and (b) the additional dipeptide WE at the C-terminus of an specified native GDF11 protein of SEQ ID NO: 20 does not represent additional a dipeptide motif of EW or a hexapeptide motif of (linking amino acid)-Trp-(any amino acid residues)0-4 comprising at least 3,200,000 different species (calculated as 205 and a tryptophan) in addition to non-natural amino acid substitutions (e.g., 5-hydroxytryptophan taught by Zhang et al. Proc Natl Acad Sci USA. 2004 Jun 8;101(24):8882–8887), a conserved substitution of tryptophan) as claimed. The examiner did not find any words, sequences, data, figures, examples and/or the overall content of the disclosure as a whole sufficient to satisfy written description requirements.
The specification failed to establish the inter-relationship between a structure/sequence of the C-terminal conjugated hexapeptide motif (X1-Trp)-X0-4 and the function of reduced number of disulfide bridges as compared to the native GDF11 protein (claim 47) or increased protein stability (claim 48). The examiner did not find any words, sequences, data, figures, examples and/or the overall content of the disclosure as a whole sufficient to satisfy written description requirements showing conjugation of a hexapeptide motif (X1-Trp)-X0-4 to the C-terminus of a GDP11 to reduce number of disulfide bridges as well as increase protein stability. In fact, a hexapeptide motif of Cys-Trp-(Cyc-Cys-Cys-Cys)0-4 encompasses the scope of the claims, which can form additional disulfide bonds and/or destabilize the protein folding structure of a conjugated GDF11 protein.
Thus, claims 41-45, 47-51, and 61 are rejected as failing to satisfy written description requirements. The rejection may be overcome by distinctly claiming a GFD11 variant protein sequence (e.g., SEQ ID NO: 20) supported by specification with satisfactory written description.
Applicant’s Arguments
Applicant asserts that the Office has failed to meet its burden to establish a prima facie case of lack of written description, by failing to take into account the record as whole, including partial structures, and other explicit support for the claimed invention (Remarks, p7, last two para to p8, para 1-2).
Paragraph [0078-0079] supports the limitation of claims 41, 42 and new claim 61 (Remarks, p8, last two para to p9, para 1-2).
While the Office seems to recognize an inter-relationship between a structure/sequence of the GDFl1 variant and a function could satisfy written description requirements, the Office has failed to consider on the record the relevant paragraphs of the specification that would support such a finding. For example, paragraph [0213] notes the presence of the variant GDF11 monomer in serum that lacks the covalently bonded disulfide bridge. This paragraph further recites, "When looking at the structure of the protein, the predicted addition adds the amino acids at the end of the C-terminus, near the site of the disulfide bridge between the two monomers, and likely disrupts the formation of the mature dimer (Fig. 5)." Applicant asserts that placement of the tryptophan one amino acid from the C-terminus of the GDFl1 protein would likewise place the added amino acids, including the tryptophan, close to the site of disulfide bridge between two GDF11 monomers (Remarks, p9, last para to p10, para 1-2).
Response to Arguments
Applicant's arguments filed 5/23/2025 have been fully considered but they are not persuasive for the reasons as follows. conjugated
Applicant’s Argument (i) is not persuasive because the reasons fail to satisfy written description described above not prima facie rejection as argued by applicant. Merely disclosed a tryptophan residue linked to a native GDF11 protein via a linking amino acid from various species does not provide relevant partial sequence structure of a hexapeptide motif (a linking amino acid)1-(Tryptophan)2-(Any amino acid)0-4 conjugated to a GFF11 protein. A peptide motif of Cys-Trp-(Cyc-Cys-Cys-Cys)0-4 encompasses the scope of the claims, which can form additional disulfide bonds and/or destabilize the protein folding structure of a conjugated GDF11 protein.
Applicant’s Argument (ii) is not persuasive because paragraph [0078-0079] merely describes the length of additional peptide sequence conjugated to the C-terminus of a GDF11 protein whereas the rejection is based on the actual peptide sequence added to the C-terminus of a GDF11. Paragraph [0078-0079] does not represent at least 3,200,000 different species (calculated as 205 and a tryptophan) in addition to non-natural amino acid substitutions (e.g., 5-hydroxytryptophan, a conserved substitution of tryptophan) as claimed. Thus, the written description is maintained.
Applicant’s Argument (iii) is not persuasive because SEQ ID NO: 20 does not support any arguments based on applicant’s assertion or claim amendment introduced NEW MATTER not support by the disclosure of record. In particular, applicant disclosed modification of either the N- or C-terminus of GDF11’s mature ligand domain would be predicted to be incompatible with preservation of protein function [0188]. Thus, applicant’s opinion "When looking at the structure of the protein, the predicted addition adds the amino acids at the end of the c-terminus, near the site of the disulfide bridge between the two monomers, and likely disrupts the formation of the mature dimer (Fig. 5)" in Remarks (p9, last para to p10, para 1-2) contradicting to the disclosure and deviating from applicant’s admission [0188] is further not persuasive.
The rejection will be continuously maintained as it is unlikely to be overcome by arguments deviated from applicant’s own disclosure and/or admission.
Examiner’s Note:
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The closest prior art reference, Gamer et al. (Developmental Biology 208, 222–232 (1999)), shows a native bone morphogenetic protein 11 (BMP-11 same as human GDF 11 protein) consisting of 407 amino acid residues (p224, Fog 1A). A protein sequence alignment of Gamer’s BMP-11 with the claimed C-terminus modified GDF-11 variant is shown as follows. Gamer et al. did not teach or suggest addition of 2 to 6 additional amino acids with a tryptophan or a conservative substitution linked to the C-terminus of a native BMP11/GDF11 protein via a linking amino acid residue (e.g., EW) as claimed. Thus, Gamer’s BMP11/GDF11 protein does not read on the claimed protein.
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Conclusion
No claim is allowed.
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/J.L/Examiner, Art Unit 1658
10-December-2025
/LI N KOMATSU/ Primary Examiner, Art Unit 1658