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 .
Election/Restrictions
1. Applicant’s election without traverse of species of a polypeptide as described within claim 17, as amended on December 14, 2025, in the reply filed on December 14, 2025 is acknowledged.
2. Claims 17-20, 23, 25, 28-33, 35, 37, 40-43, 52, 53, 79 and 80 are pending.
Claims 17-20, 23, 25, 28-33, 35, 37, 40-43, 52, 53, 79 and 80 are under examination.
Sequence compliance
3. This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 C.F.R. § 1.821 (a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 C.F.R. § 1.821 through 1.825. Specifically, no sequence identification has been provided for the amino acid sequences presented at p. 35, lines 15, 17 and 21, and at p. 36, lines 57-63 of the instant specification. In case these sequences are new, Applicant needs to provide a substitute computer readable form (CRF) copy of a “Sequence Listing” which includes all of the sequences that are present in the instant application and encompassed by these rules, a substitute paper copy of that “Sequence Listing”, an amendment directing the entry of that paper copy into the specification, and a statement that the content of the paper and computer readable copies are the same and, where applicable, include no new matter, as required by 37 C.F.R. § 1.821 (e) or 1.821(f) or 1.821(g) or 1.825(b) or 1.825(d). The instant specification will also need to be amended so that it complies with 37 C.F.R. § 1.821(d) which requires a reference to a particular sequence identifier (SEQ ID NO: ) be made in the specification and claims wherever a reference is made to that sequence. See MPEP 2422.04.
Specification
4. The use of the term Alexa Fluor, which is a trade name or a mark used in commerce, has been noted in this application, p 39. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Applicant is advised to review the entire text of the specification for proper citation of trade names.
Claim Objections
5. Claim 17 is objected to because of the following informalities:
The claim recites “TrkB-FL” and “TrkB-ICD” without first providing the full name of the terms. It is suggested that the terms be spelled out at their first use and in all independent claims so that it is clearly understood what they stand for. Appropriate correction is suggested.
6. Claims 43 and 80 are objected to because of the following informalities: the claims do not end with a period. MPEP 608.01(m), Form of Claims, states:
Each claim begins with a capital letter and ends with a period.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
7. Claims 17-20, 23, 25, 28-33, 35, 37, 40-43, 52, 53, 79 and 80 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.
8. Claim 17 is indefinite because it is written to encompass a product of vague and ambiguous structure. Specifically, the structure of the polypeptide claimed within is defined by reference to “a portion of TrkB-FL,” and by reference to origin, “derived from SEQ ID NO: 1.” First, the relationship between Trk-B and SEQ ID NO: 1 is not clear. Second, the metes and bounds of the limitation “derived from” within the context of a product cannot be determined from the claim or the specification as filed. Next, Applicant is advised that “SEQ ID NO:” is a sequence identifier and not a product itself. As such, it cannot be a source of derivation for the claimed polypeptide. Finally, it is not obvious whether residues “Asn 520 and Ser 521” are recited with respect to their position within the amino acid sequence of SEQ ID NO: 1 or within the sequence of the polypeptide that is the claimed product. Applicant is advised to rewrite the claim so that every element or ingredient of the claimed product is set forth in positive, exact, intelligible language, so that there is no uncertainty about what it means.
9. Next, claim 17 recites the limitation "the isolated portion". There is insufficient antecedent basis for this limitation within the claim, see claim as amended to recite “a portion.”
10. Further, claim 17 recites limitation “wherein the isolated portion of TrkB-FL spans the calpain cleavage site of TrkB-FL to produce TrkB-ICD,” which is considered functional language. MPEP 2173.05(g) states: “the use of functional language in a claim may fail ‘to provide a clear-cut indication of the scope of the subject matter embraced by the claim' and thus be indefinite.” It further states: “Examiners should consider the following factors when examining claims that contain functional language to determine whether the language is ambiguous: (1) whether there is a clear cut indication of the scope of the subject matter covered by the claim; (2) whether the language sets forth well-defined boundaries of the invention or only states a problem solved or a result obtained; and (3) whether one of ordinary skill in the art would know from the claim terms what structure or steps are encompassed by the claim.” In the instant case, the claim encompasses a product but then defines its structure by reference to a process—to produce TrkB-ICD—functional language. While a functional limitation can provide a patentable distinction (limit the claim scope) by imposing limits on the function of a structure, material or action, in the instant case it is unclear what material/structural or manipulative differences are encompassed by description of inclusion of “the calpain cleavage site […] to produce” TrkB-ICD. Since the claim fails to meet the criteria set forth in MPEP 2173.05(g), then the claim is rejected as being indefinite.
11. Finally, claim 17 recites “TrkB-ICD,” which appears the resulting fusion polypeptide; however, the relationship between the claimed polypeptide and “TrkB-ICD” is not obvious.
12. Similarly to claim 17 earlier, see section 10 earlier, claim 28 is indefinite for reciting limitation “the polypeptide suitable for delivery,” because it adds a functional limitation to the polypeptide of the base claim 17 without providing any material structural difference to distinguish the claims.
13. Claim 29 is vague and ambiguous for reciting “a cell-penetrating peptide” while being dependent from claim 17, which already comprises a cell-penetrating peptide. This renders the claim indefinite because it is not clear whether the claim adds a second cell-penetrating peptide to the structure described within the base claim.
14. Similarly to claim 29 above, claim 32 recites “a linker,” wherein the polypeptide of the base claim 17 already has a linker. This renders the structure of the product of claim 32 indefinite.
15. Claim 35 is interpreted as an attempt to describe the structure of the polypeptide by reference to three amino acid sequences. However, the claim, as presented is prone to multiple interpretation because it is not obvious whether these sequences are intended in particular order, or they are parts of longer polypeptides, see “comprising;” thus making the claimed product vague and ambiguous.
16. Claim 53 is vague and indefinite insofar as it employs the terms “pathology characterized by excitotoxicity,” “pathology related to TrkB-FL cleavage” and “other types of peripheral neuropathy” as limitations. These terms are not known in the relevant prior art of record as being associated with well-defined genus of clinical pathologies. Moreover, because the instant specification does not identify that property or combination of properties which is unique to and, therefore, definitive of a “pathology characterized by excitotoxicity,” “pathology related to TrkB-FL cleavage” and “other types of peripheral neuropathy,” an artisan cannot determine if a pathology which meets all of the other limitations of a claim would then be included or excluded from the claimed subject matter by the presence of this limitation.
17. Claims 18-20, 23, 25, 30, 31, 33, 37, 40-43, 52, 79 and 80 are indefinite for being dependent from indefinite claim(s).
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), fourth paragraph:
Subject to the [fifth paragraph of 35 U.S.C. 112 (pre-AIA )], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
18. Claims 40, 41, 79 and 80 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 40, 41, 79 and 80 23 depend from claim 17, which is limited to a polypeptide, while the dependent claims recite nucleic acids, the product not present within the claim from which they depend. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
19. Claims 17-20, 23, 25, 28-33, 35, 40-43, 52, 53, 79 and 80 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.
Claims 17-20, 23, 25, 28-33, 35, 40-43, 52, 53, 79 and 80 encompass a genus of polypeptides defined as comprising a portion of TrkB-FL that is derived from SEQ ID NO: 1, comprises Asn 520 and Ser 521, and is 5 to 20 residues in length; a linker; and a cell penetrating peptide that is connected to the portion of TrkB-FL by the linker; wherein the isolated portion of TrkB- FL spans the calpain cleavage site of TrkB-FL, and wherein the polypeptide is able to prevent calpain cleavage of TrkB FL to produce TrkB-ICD. The polypeptides within the genus are further defined by reference to the amino acid sequence of SEQ ID NOS: 18, 19 and 20 with one or more substitutions, conservative substitutions, modifications or replacements. The claims appear to define the conserved structure by reference to calpain cleavage site; however, in view of the use of indefinite language, see sections 8-11 earlier, this structure remains vague and ambiguous, and thus, not described.
MPEP §2163(I)(A) states:
“The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional or known in the art. Consider the claim "A gene comprising SEQ ID NO:1." The claim may be construed to include specific structures in addition to SEQ ID NO:1, such as a promoter, a coding region, or other elements. Although SEQ ID NO:1 is fully disclosed, there may be insufficient description of other structures embraced by the claim (e.g., promoters, enhancers, coding regions, and other regulatory elements).”
“An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. For example, the amino acid sequence of a protein along with knowledge of the genetic code might put an inventor in possession of the genus of nucleic acids capable of encoding the protein, but the same information would not place the inventor in possession of the naturally-occurring DNA or mRNA encoding the protein. See In re Bell, 991 F.2d 781, 26 USPQ2d 1529 (Fed. Cir. 1993); In re Deuel, 51 F.3d 1552, 34 USPQ2d 1210 (Fed. Cir. 1995) (holding that a process could not render the product of that process obvious under 35 U.S.C 103).”
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, it is necessary to understand what Applicant has possession of and what Applicant is claiming. From the specification, it is clear that Applicant has possession of polypeptides comprising the amino acid sequence of SEQ ID NO: 1, 5, 12, 18-24 and 26-28. The claims are drawn to polypeptides comprising a portion of TrkB-FL that is derived from SEQ ID NO: 1, comprises Asn 520 and Ser 521, and is 5 to 20 residues in length; a linker; and a cell penetrating peptide that is connected to the portion of TrkB-FL by the linker; wherein the isolated portion of TrkB- FL spans the calpain cleavage site of TrkB-FL, wherein the polypeptide is able to prevent calpain cleavage of TrkB FL to produce TrkB-ICD, as well as polypeptides that have substitutions, conservative substitutions, modifications or replacements within the amino acid sequences of SEQ ID NO: 18, 19 and 20. Thus, the claims are not limited to a protein with a specific amino acid sequence. The claims only require the claimed polypeptides to share some degree of structural similarity to the protein of SEQ ID NO: 1 and to have the activities to satisfy the asserted utility requirement of the instant invention—being useful to treat various pathologies upon clinical administration. The specification only describes polypeptides having the amino acid sequence of SEQ ID NO: 22, 23, 24, 26, 27 and 28 and fails to teach or describe any other protein which is derived from SEQ ID NO: 1 and has the activities required to practice the invention as claimed.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of polypeptides, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
20. Claims 52 and 53 are further rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method for treating a subject affected by Alzheimer’s disease (AD) by administering a therapeutically effective amount of a polypeptide comprising an amino acid sequence of SEQ ID NO: 22, 23, 24, 26, 27, or 28, does not reasonably provide enablement for the full scope of the claimed methods. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
Claims 52 and 53 are broadly drawn to methods of treating subjects affected by AD and subjects “affected by a neuropathological condition, a pathology characterized by excitotoxicity, epilepsy, prion-like diseases, muscular dystrophies, Huntington's disease, Parkinson's disease, multiple sclerosis, ischemia, stroke, brain trauma, a pathology related to TrkB-FL cleavage, depression, anxiety, bipolar disorders, schizophrenia, obesity, autism, rett syndrome, retinal ganglion cell loss, ageing, amyotrophic lateral sclerosis (Lou Gehrig's disease), the adverse neurologic complications of Down syndrome, diabetic peripheral neuropathy, or other types of peripheral neuropathy” by administration of a polypeptide comprising a “portion of TrkB-FL that is derived from SEQ ID NO: 1, comprises Asn 520 and Ser 521, and is 5 to 20 residues in length; a linker; and a cell penetrating peptide that is connected to the portion of TrkB-FL by the linker; wherein the isolated portion of TrkB- FL spans the calpain cleavage site of TrkB-FL, and wherein the polypeptide is able to prevent calpain cleavage of TrkB FL to produce TrkB-ICD.” However, the specification does not provide sufficient guidance to enable practice the full scope of the claimed invention without undue experimentation.
The enablement requirement is met when one skilled in the art, having read the specification, could practice the invention without “undue experimentation.” Cephalon, Inc. v. Watson Pharm., Inc., 707 F.3d at 1336 (Fed. Cir. 2013). The factors to be considered in determining whether a disclosure would require undue experimentation include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art and, (8) the breadth of the claims. In re Wands, 8 USPQ2d, 1400 (CAFC 1988).
The specification describes significance of BDNF impaired signaling during pathology of AD, pp. 1 and 34, for example. The invention is a demonstration “that TrkB-FL cleavage increases during AD progression,” and further the “design of a small TAT-TrkB peptide that prevents this cleavage and restores BDNF physiological actions on synaptic transmission and plasticity,” p. 34. Working Examples at pp. 34-43 disclose the design and production of the peptides of the invention and their effect on release of glutamate in vitro and improvement of memory in vivo when using art-recognized AD model, 5xFAD. The specification fails to provide any further information that would allow one of skill in the art to extrapolate the information limited to the specific peptides and to the Alzheimer’s pathology only to any one of the diseases or disorders recited within claim 53 or to the use of polypeptides that currently lack adequate written description within the specification as originally filed, see section 19 earlier.
The nature of the invention involving biological molecules and their effect on a physiological system is complex and unpredictable. As was found in Ex parte Hitzeman, 9 USPQ2d 1821 (BPAI 1987), a single embodiment may provide broad enablement in cases involving predictable factors such as mechanical or electrical elements, but more will be required in cases that involve unpredictable factors such as most chemical reactions and physiological activity. This invention is in a class of invention which the CAFC has characterized as "the unpredictable arts such as chemistry and biology", Mycogen Plant Sci., Inc. v. Monsanto Co., 243 F.3d 1316, 1330 (Fed. Cir. 2001). See also In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970); Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 927 F.2d 1200, 1212, 18 USPQ2d 1016, 1026 (Fed. Cir.), cert. denied, 502 U.S. 856 (1991).
The prior art does not recognize the pathologies recited within claim 53 as obvious variants of one another. The disorders rather encompass a broad range of pathological conditions of substantial phenotypic, pathophysiological, epidemiological and etiological heterogeneity for which treatment of one does not constitute an effective treatment for another.
With respect to claim breadth, the standard under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, entails the determination of what the claims recite and what the claims mean as a whole. In addition, when analyzing the enablement scope of the claims, the teachings of the specification are to be taken into account because the claims are to be given their broadest reasonable interpretation that is consistent with the specification (see MPEP 2111 [R-1], which states that claims must be given their broadest reasonable interpretation. “During patent examination, the pending claims must be "given *>their< broadest reasonable interpretation consistent with the specification." In re Hyatt, 211 F.3d 1367, 1372, 54 USPQ2d 1664, 1667 (Fed. Cir. 2000). Applicant always has the opportunity to amend the claims during prosecution, and broad interpretation by the examiner reduces the possibility that the claim, once issued, will be interpreted more broadly than is justified. In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550- 51 (CCPA 1969).”
As such, the broadest reasonable interpretation of the claimed methods is that they allow treatment of AD, neuropathological conditions in general, pathologies characterized by excitotoxicity, epilepsy, prion-like diseases, muscular dystrophies, Huntington's disease, Parkinson's disease, multiple sclerosis, ischemia, stroke, brain trauma, a pathology related to TrkB-FL cleavage, depression, anxiety, bipolar disorders, schizophrenia, obesity, autism, Rett syndrome, retinal ganglion cell loss, ageing, amyotrophic lateral sclerosis (Lou Gehrig's disease), the adverse neurologic complications of Down syndrome, diabetic peripheral neuropathy, and other types of peripheral neuropathy, all by administration of fusion proteins comprising a portion of a protein that is derived from a polypeptide of SEQ ID NO:1 . Thus, the claims encompass an unreasonable number of pathological conditions to be treated by administration of broad range of polypeptides of ambiguous structure, which the skilled artisan would not know how to evaluate. As opposed to the claims, what is disclosed about the claimed method is narrow: a set of experimental results related to AD and specifically identified polypeptides and no other obvious specific examples of disorders, polypeptides suitable for immediate clinical administration or guidance as how to practice the full scope of instant claimed methods.
The standard of an enabling disclosure is not the ability to make and test if the invention worked but one of the ability to make and use with a reasonable expectation of success.
A patent is granted for a completed invention, not the general suggestion of an idea and how that idea might be developed into the claimed invention. If mere plausibility were the test for enablement under section 112, applicants could obtain patent rights to “inventions” consisting of little more than respectable guesses as to the likelihood of their success. In the decision of Genentec, Inc, v. Novo Nordisk, 42 USPQ 2d 100, (CAFC 1997), the court held that:
“[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable” and that “[t]ossing out the mere germ of an idea does not constitute enabling disclosure.” The court further stated that “when there is no disclosure of any specific starting material or of any of the conditions under which a process is to be carried out, undue experimentation is required; there is a failure to meet the enablement requirements that cannot be rectified by asserting that all the disclosure related to the process is within the skill of the art,” “[i]t is the specification, not the knowledge of one skilled in the art, that must supply the novel aspects of an invention in order to constitute adequate enablement.”
The instant specification is not enabling because one cannot follow the guidance presented therein and practice the claimed methods without first making a substantial inventive contribution to perfect the method and complete the invention.
Conclusion
21. No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to OLGA N CHERNYSHEV whose telephone number is (571)272-0870. The examiner can normally be reached 9AM to 5:30PM, Monday to Friday.
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/OLGA N CHERNYSHEV/Primary Examiner, Art Unit 1675
March 4, 2026