The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This office action is in response to Applicants’ amendments/remarks received May 29, 2026.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn.
Claims 7-8, 11-14, 17, 20, 29-30 are canceled. Claims 15-16, 18-19, 21-28 are withdrawn. Claims 1-6, 9-10 are under consideration.
Priority: This application is a 371 of PCT/US2021/059427, filed November 15, 2021, which claims benefit of provisional application 63/113267, filed November 13, 2020.
Objections and Rejections
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-6, 9-10 are rejected under 35 U.S.C. 101 because the claimed invention is not directed to patent eligible subject matter. The instant claims are product claims reciting titin proteins that are not markedly different from naturally occurring titin proteins.
Claims 1-5 are directed to a microbially-synthesized titin protein comprising a plurality of folded immunoglobulin-like (Ig-like) domains and claims 6, 9-10 are directed to a titin fiber comprising the microbially-synthesized titin protein. The patentability of a product does not depend on its method of production, i.e. a product-by-process is not limited to manipulation of the recited steps, but instead is limited to the structure implied by the steps. MPEP 2113. The limitation “microbially-synthesized” is a process by which the titin protein is produced. The claims include titin proteins or polypeptides having amino acid structures that are the same as mammalian titin proteins. The claims are directed to a statutory category, i.e. a composition of matter (step 1: YES).
Since the claims recite a nature-based product, i.e. a titin protein and/or titin fiber, the claims are analyzed to determine whether it is directed to any judicial exception. The markedly different characteristics analysis is performed by comparing the nature-based product limitation in the claim to its naturally occurring counterpart to determine if it has markedly different characteristics from the counterpart. The recited titin proteins and/or titin fibers are compared to its closest naturally occurring counterpart(s) to determine if it has markedly different characteristics. Here, the closest natural counterpart is naturally occurring titin protein and/or titin fiber. When the claimed titin protein and/or titin fiber is compared to this counterpart, the comparison indicates that there are no differences in structure, function, or other characteristics. Human muscle tissue comprises titin protein and/or titin fiber having 112 Ig-like domain folds (Labeit et al. p. 293, 295). There is no indication that the claimed titin protein comprising a plurality of folded Ig-like domains is a titin protein having any structural and/or functional characteristics that are different from the naturally occurring titin protein and fiber in its natural state. Therefore, the claimed titin protein and fiber do not have markedly different characteristics from what occurs in nature and is a “product of nature” exception. Accordingly, the claim is directed to an exception (step 2A: YES). Next, the claims as a whole are analyzed to determine whether any additional element, or combination of elements, is sufficient to ensure that the claim amounts to significantly more than the exception(s). The claims do not recite anything significantly different than the natural product, i.e. the claims do not recite elements or features that demonstrate that the claimed titin protein comprising a plurality of folded Ig-like domains is markedly different from what exists in nature. The claims are amended to recite that the plurality of folded Ig-like domains form a network of non-covalently cross-linked β-sheet crystals. However, the formation of non-covalently cross-linked β-sheet crystals are a feature of the plurality of folded Ig-like domains. Therefore, the claims as a whole add nothing significantly more to the “product of nature” itself (Step 2B: NO), and thus, the claim does not qualify as eligible subject matter.
See also Funk Brothers Seed Co., V. Kalo Inoculant Co., 333 U.S. 127, (1948) and Association for Molecular Pathology v. Myriad Genetics, Inc. 569 U.S., 133 S. Ct. 2107, 2116, 106 USPQ 2d. 1972 (2013).
Reply: Applicants’ amendments/remarks have been considered but they are not persuasive.
Applicants assert that claim 1 has been amended for precision to recite that the plurality of folded Ig-like domains form a network of non-covalently cross-linked β-sheet crystals.
Applicants’ remarks are not persuasive. As noted in the 101 rejection above, human muscle tissue comprises titin protein and/or titin fiber having 112 Ig-like domain folds (Labeit et al. p. 293, 295). While the claims are amended to recite that the plurality of folded Ig-like domains form a network of non-covalently cross-linked β-sheet crystals, it is known that the formation of non-covalently cross-linked β-sheet crystals are a feature of the plurality of folded Ig-like domains. The Ig domain folds consist of two β-sheet strands packing against each other, with each sheet containing four strands; this structure is stabilized by hydrophobic core interactions between the β-sheets and by hydrogen bonds between β-strands (Lu et al. p. 663). Therefore, the claims as a whole add nothing significantly more to the “product of nature” itself, and thus, the claim does not qualify as eligible subject matter.
As also acknowledged by Applicants’ remarks, the microbially produced muscle titin recaptures highly desirable properties of natural titin (i.e. high damping capacity and mechanical recovery) (Applicants’ remarks p. 7).
Applicants assert that the microbially produced muscle titin also exhibit exceptionally high strength, toughness, and damping energy-outperforming many synthetic and natural polymers.
Applicants’ remarks are not persuasive because there is no indication that the many synthetic and natural polymers noted by Applicants is a natural titin, which also has a plurality of Ig-like domain folds (Labeit et al.). In other words, there is no indication that the claimed titin protein comprising a plurality of folded Ig-like domains exhibits exceptionally high strength, toughness, and damping energy which outperforms natural titin protein.
Applicants assert that the measured properties of the microbially produced muscle titin outperform naturally occurring titin. Applicants point to paragraphs 0100-0104 of the published application.
Applicants’ remarks are not persuasive because this is not a proper comparison. Paragraphs 0100-0104 compare the properties of synthesized titin fibers (i.e. titin proteins spun into fibers) to a natural single titin molecule, where the titin fibers have improved properties over natural single titin molecule. However, when the synthesized titin fibers are compared to natural titin in the muscle, the synthesized titin fibers recover mechanical properties in a manner reminiscent of natural titin and muscle fiber (application publication paragraph 0101). Further, as acknowledged in the specification, the microbially produced titin protein is qualitatively similar to natural titin protein extracts and having nanoscale fibrils with apparent chain-of-beads structures and cross-sectional diameters that were similar to those previously observed for natural titin proteins (application publication paragraph 0094). Paragraph 0094 further discloses that together, these results indicate that the microbially produced titin have a substantial degree of folded structures similar to natural Ig domains (hereinafter called Ig-like structures).
Therefore, there is no indication that the claimed titin protein comprising a plurality of folded Ig-like domains is a titin protein having any structural and/or functional characteristics that are different from the naturally occurring titin protein and fiber in its natural state.
For at least these reasons, the 101 rejection is maintained.
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-6, 9-10 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Trinick et al. (1984 J Mol Biol 180: 331-356; previously cited), and evidenced by Labeit et al. (1995 Science 270: 293-296; previously cited). The instant claims are product-by-process claims. As noted above, the limitation “microbially-synthesized” is a process by which the titin protein is produced. The patentability of a product does not depend on its method of production, i.e. a product-by-process is not limited to manipulation of the recited steps, but instead is limited to the structure implied by the steps. MPEP 2113.
Trinick et al. teach a preparation comprising native titin protein or polypeptides, where the chain molecular weight of titin is ~106 Mr (at least p. 331-332, 350; instant claims 1-4), where the titin protein inherently comprises 112 Ig-like domains (evidenced by Labeit et al. p. 293).
Regarding the instant limitation that the plurality of folded Ig-like domains form a network of non-covalently cross-linked β-sheet crystals (instant claim 1), it is noted that the formation of non-covalently cross-linked β-sheet crystals are a feature or property of the plurality of folded Ig-like domains. In this instance, since the titin protein inherently comprises 112 Ig-like domains, it would follow that the plurality of the Ig-like domains form a network of non-covalently cross-linked β-sheet crystals.
Regarding instant claim 5, Trinick et al. teach the longest titin strands contain several polypeptide chains of weight ~106 (p. 350); therefore, Trinick et al. can be deemed to teach the native titin protein has a mass average molecular weight of at least 2 MDa.
Regarding instant claim 6, Trinick et al. teach rabbit muscle comprising myofibrils and titin protein (at least p. 332). Therefore, Trinick et al. can be deemed to teach a fiber comprising a titin protein comprising a plurality of Ig-like domains. Regarding instant claims 9-10, since Trinick et al. teach a titin fiber comprising the same structural features recited, including the recited titin protein comprising a plurality of Ig-like domains, it would follow that the muscle fibers comprising titin protein of Trinick et al. have the same properties of toughness and ultimate tensile strength recited in the instant claims. MPEP 2112.01 notes that a chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present.
Reply: Applicants’ amendments/remarks have been considered but they are not persuasive.
Applicants assert that claim 1 has been amended for precision to recite that the plurality of folded Ig-like domains form a network of non-covalently cross-linked β-sheet crystals.
Applicants’ remarks are not persuasive. As noted in the 102(a)(1) rejection above, Trinick et al. teach a preparation comprising native titin protein or polypeptides, where the chain molecular weight of titin is ~106 Mr (at least p. 331-332, 350), where the titin protein inherently comprises 112 Ig-like domains (evidenced by Labeit et al. p. 293).
While the claims are amended to recite that the plurality of folded Ig-like domains form a network of non-covalently cross-linked β-sheet crystals, it is known that the formation of non-covalently cross-linked β-sheet crystals are a feature of the plurality of folded Ig-like domains. The Ig domain folds consist of two β-sheet strands packing against each other, with each sheet containing four strands; this structure is stabilized by hydrophobic core interactions between the β-sheets and by hydrogen bonds between β-strands (Lu et al. p. 663).
In this instance, since the titin protein of Trinick et al. inherently comprises 112 Ig-like domains, it would follow that the plurality of the Ig-like domains form a network of non-covalently cross-linked β-sheet crystals.
For at least these reasons, the 102(a)(1) rejection is maintained.
Claims 1-3 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Garcia et al. (2009 Proteins 75: 706-718; previously cited). Garcia teach a I27 is an Ig-like domain repeated ~40 times in the I-band of human cardiac N2-B titin (at least p. 707, also Fig. 1). Garcia et al. teach I27 polyproteins with multiple number of I27 domains, with up to 20 (at least p. 708; instant claims 1-3).
Reply: Applicants’ amendments/remarks have been considered but they are not persuasive. The reasons for maintaining Garcia et al. are the same as similarly noted above.
While the claims are amended to recite that the plurality of folded Ig-like domains form a network of non-covalently cross-linked β-sheet crystals, it is known that the formation of non-covalently cross-linked β-sheet crystals are a feature of the plurality of folded Ig-like domains. The Ig domain folds consist of two β-sheet strands packing against each other, with each sheet containing four strands; this structure is stabilized by hydrophobic core interactions between the β-sheets and by hydrogen bonds between β-strands (Lu et al. p. 663).
In this instance, since the I27 protein of Garcia et al. inherently comprises a plurality of Ig-like domains, it would follow that the plurality of the Ig-like domains form a network of non-covalently cross-linked β-sheet crystals.
For at least these reasons, the 102(a)(1) rejection is maintained.
No claim is allowed.
THIS ACTION IS MADE FINAL. 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.
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/Marsha Tsay/Primary Examiner, Art Unit 1656
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