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 .
DETAILED ACTION
Claim Status
This action is in response to the amended claim set filed on 02/10/2025. Claims 1-6 are pending and are considered on the merits.
Priority
This application is a 371 of PCT/JP2023/024103 (filed on 06/29/2023), which claims benefit from foreign application JP 2022-137043 (filed on 08/30/2022). The priority claim of the instant application has been granted and the earliest benefit date is 08/30/2022 from the application JP 2022-137043.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 02/10/2025 and 07/13/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner. The corresponding signed and initialed PTO forms 1449 have been mailed with this action.
Claim Objections
Claims 1-2 and 5 are objected to because of the following informalities:
Claim 1 recites “a lysine residue at a 12th position from an N-terminus of the amino acid sequence”. Since the amino acid sequence has a defined sequence (i.e., SEQ ID NO: 1), it is recommended to change the phrase to “the lysine residue at the 12th position from the N-terminus of the amino acid sequence”.
Claim 2 recites “the N-terminus and/or a C-terminus”. It is recommended to change to “the N-terminus and/or the C-terminus”.
Claim 5 recites “a cytoplasm of the cell”. It is recommended to change to “the cytoplasm of the cell”.
Additionally, claim 5 recites “a target eukaryotic cell” in the last line. Since a eukaryotic cell has been recited in line 2, it is recommended to change to “the eukaryotic cell”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
(Written Description)
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 1-6 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
Specifically, instant claims encompass a genus of carrier peptide fragments comprising the amino acid sequence of SEQ ID No.: 1 with the lysine at the 12th position being D-form. Applicant is reminded that the transitional term “comprising” is inclusive or open-ended and does not exclude additional, unrecited elements or method steps. See MPEP 2111.03 (I). Therefore, the instant invention encompasses a genus of carrier peptide fragments comprising the claimed amino acid sequence of SEQ ID No: 1 (with the lysine at the 12th position being D-form and the other residues being L-forms) with addition of any amino acid sequences upstream or downstream of this sequence.
However, the specification only discloses a single species of carrier peptide fragment consisting of the amino acid sequence of SEQ ID NO: 1 with the lysine at the 12th position being D-form and the other residues being L-forms that has remarkably improved cell membrane permeation rate (see [0052], Table 2 row “Example 12” attached for the sequence and Fig 1 for permeation rate).
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Under the written description guidelines (see MPEP 2163) the Examiner is directed to determine whether one skilled in the art would recognize that the Applicant was in possession of the claimed invention as a whole at the time of filing. The following considerations are critical to this determination.
To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116. An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). The written description requirement is not necessarily met when the claim language appears in ipsis verbis in the specification. "Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement." Enzo Biochem, Inc. v. Gen-Probe, Inc., 323 F.3d 956, 968, 63 USPQ2d 1609, 1616 (Fed. Cir. 2002).
Accordingly, to satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.
SCOPE OF THE INVENTION
Independent claim 1 encompasses a genus of carrier peptide fragments comprising the claimed amino acid sequence of SEQ ID No: 1 (with the lysine at the 12th position being D-form and the other residues being L-forms) with addition of any other amino acid sequences upstream or downstream of the sequence, and this genus of carrier peptide fragments is bonded to a foreign substance to transfer the substance into the cytoplasm of a eukaryotic cell. However, the specification only discloses a single species of carrier peptide fragment consisting of the amino acid sequence of SEQ ID NO: 1 with the lysine at the 12th position being D-form and the other residues being L-forms that is bonded to a foreign substance to transfer the substance into the cytoplasm of a eukaryotic cell at a remarkably improved rate (see [0052], Table 2 row “Example 12” attached for the sequence and Fig 1 for permeation rate).
Dependent claims 2-6 encompass a construct comprising the carrier peptide fragment and a foreign substance that is bonded to the fragment, the substance being an organic compound, being disposed on the C-terminus of the fragment, and a method for transferring a foreign substance into the cytoplasm of a eukaryotic cell by supplying the construct into a sample including the cell, the cell being a mammalian cell. However, the specification only discloses a combination of the limitations (see above).
ACTUAL REDUCTION TO PRACTICE
Accordingly, Applicant did not demonstrate a reduction to practice of a genus of carrier peptide fragments comprising the claimed amino acid sequence of SEQ ID No: 1 (with the lysine at the 12th position being D-form and the other residues being L-forms) with any amino acid sequences upstream or downstream of the sequence, nor did Applicant adequately set forth in terms of distinguishing identifying characteristics as evidenced by other descriptions of the invention that are sufficiently detailed to show that Applicant was in possession of the claimed genus of carrier peptide fragments.
DISCLOSURE OF STRUCTURE
The Applicant claims a genus of carrier peptide fragments comprising the claimed sequence and forms with any other amino acid sequences upstream or downstream of the sequence, but has provided no other carrier peptide fragments than the specific carrier peptide fragment consisting of the claimed sequence and forms. Certainly, a skilled artisan could make a carrier peptide fragment comprising the claimed sequence and forms and could add any other amino acids upstream and downstream of the sequence. However, the prior art is silent on the genus of resulted carrier peptide fragments having cell membrane permeation ability. Furthermore, neither the specification nor the art indicates a relationship between the structure of the claimed genus of carrier peptide fragments and the cell membrane permeation ability.
SUFFICIENT RELEVANT IDENTIFYING CHARACTERISTICS
As mentioned above, the skilled artisan could make a carrier peptide fragment comprising the claimed sequence and forms with addition of any other amino acids upstream and downstream of the sequence. However, the prior art is silent on the genus of resulted carrier peptide fragments having cell membrane permeation ability.
The breadth of the claims encompasses a genus of carrier peptide fragments comprising the claimed sequence and forms with any other amino acid sequences upstream or downstream of the sequence, yet the present specification provides no guidance nor description on what amino acid sequences can be added upstream or downstream of the sequence and still makes a carrier peptide fragment that has cell membrane permeation ability. Therefore, the skilled artisan would not know what rational approach to take to make the genus of carrier peptide fragments, with any predictable outcome on its possession of cell membrane permeation ability. Therefore, it is incumbent on the applicant to provide this nexus between structure and function, in order to be given credit for possession of the claimed genus of carrier peptide fragments comprising the claimed sequence and forms with any other amino acid sequences upstream or downstream of the sequence.
An applicant may show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. Enzo Biochem, 323 F.3d at 964, 63 USPQ2d at 1613.
STATE OF THE ART & QUANTITY OF EXPERIMENTATION
The making and using the claimed invention is not well established. Although the making of carrier peptide fragments was known in the state of the art, one of skill in the art would neither expect nor predict the appropriate cell membrane permeation ability produced according to the claimed genus of carrier peptide fragments.
Prior art Goyal et al., (J Biol Chem. 2006;281(35):25223-25230) discloses a unique nuclear and nucleolar localization signal of LIM Kinase 2 “KKRTLRKNDRKKR” motif (that is similar to the instantly claimed sequence of KKRTLRKSNRKKR in instant SEQ ID NO: 1) and teaches “After fusing this motif to enhanced green fluorescent protein, the fusion protein localized exclusively in the nucleus and nucleolus” (e.g., abstract). However, Goyal further teaches “LIMK1 and LIMK2 are localized predominantly in the cytoplasm” (p. 25223, right col, para 2. It is noted that LIMK2 comprises the motif at amino acids 491-503 (abstract), i.e., the motif in LIMK2 cannot localize the full-length LIMK2 in the nucleus and nucleolus, as distinct from the motif-EGFP fusion protein), indicating that adding any amino acid sequences upstream or downstream of the motif (such as in the full-length LIMK2 protein) would likely compromise its function (such as the nuclear and nucleolar localization ability). Accordingly, Goyal evidences that making and using the claimed carrier peptide fragments, that comprise the claimed sequence and form with addition of any amino acid sequences upstream or downstream of the sequence, for transferring a foreign substance into a cell, was not well established.
Applicant has claimed a genus of carrier peptide fragments comprising the claimed sequence and forms with any other amino acid sequences upstream or downstream of the sequence for transferring a foreign substance into a cell, yet the present specification has not disclosed such carrier peptide fragments other than the specific carrier peptide fragment consisting of the claimed sequence and forms that has cell membrane permeation ability, has not set forth in terms of distinguishing identifying characteristics as evidenced by other descriptions of the invention that are sufficiently detailed to show that Applicant was in possession of the claimed genus of carrier peptide fragments. Furthermore, the state of the art indicated that making and using the claimed genus of carrier peptide fragments for transferring a foreign substance into a cell is not well established and would require undue experimentation, and one of skill in the art would neither expect nor predict the claimed function of transferring a foreign substance into a cell produced according to the claimed genus of carrier peptide fragments comprising the claimed amino acid sequence and forms with addition of any other amino acid sequences upstream or downstream of the sequence.
CONCLUSION
The Examiner concludes that there is insufficient written description of the instantly claimed genus of carrier peptide fragments comprising the claimed sequence and forms with addition of any other amino acid sequences upstream or downstream of the sequence for transferring a foreign substance into a cell. Specifically, Applicant has only provided one single species of the specific carrier peptide fragment consisting of the claimed amino acid sequence and forms that has cell membrane permeation ability, thus does not provide sufficient number of species to represent the entire scope of the claimed extremely broad genus of carrier peptide fragments. Therefore, the Examiner concludes that there is insufficient written description to show that Applicant was in possession of the claimed genus of carrier peptide fragments comprising the claimed sequence and forms with addition of any other amino acid sequences upstream or downstream of the sequence for transferring a foreign substance into a eukaryotic cell.
(Scope of Enablement)
Claims 5-6 are 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 transferring a target foreign substance from outside a eukaryotic cell into at least the cytoplasm of the cell, the method comprising the steps of (1) preparing a construct, and (2) supplying the construct into a sample including the eukaryotic cell, wherein the construct comprises a carrier peptide fragment and a foreign substance that is bonded to the N-terminus and/or C-terminus of the carrier peptide fragment (i.e., instant claim 2), wherein the carrier peptide fragment consists of the amino acid sequence of SEQ ID No: 1: KKRTLRKSNRKKR, wherein the lysine residue at the 12th position from the N-terminus of the amino acid sequence is a D-form and the other amino acid residues are L-forms (i.e., instant claim 1) (see [0052], Table 2 row “Example 12” attached above for the sequence and Fig 1 for permeation rate), does not reasonably provide enablement for a method for transferring a target foreign substance from outside a eukaryotic cell into at least the cytoplasm of the cell using a genus of carrier peptide fragments comprising the amino acid sequence of SEQ ID No: 1: KKRTLRKSNRKKR (with the lysine residue at the 12th position being a D-form and the other amino acid residues being L-forms) with addition of any amino acid sequences upstream or downstream of this sequence. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The Court in Wands states: “Enablement is not precluded by the necessity for some 'experimentation.'” Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single simple factual determination, but rather is a conclusion reached by weighing many factual considerations.” (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or 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. While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
The office has analyzed the specification in direct accordance to the factors outlined in In re Wands. MPEP 2164.04 states: "[W]hile the analysis and conclusion of a lack of enablement are based on factors discussed in MPEP 2164.01(a) and the evidence as whole, it is not necessary to discuss each factor in written enablement rejection." These factors will be analyzed, in turn, to demonstrate that one of ordinary skill in the art would have had to perform "undue experimentation" to use the invention and therefore, Applicant's claims are not enabled commensurate with the scope of the invention.
SCOPE OF THE INVENTION
The breadth of the claims encompasses a genus of method for transferring a target foreign substance from outside a eukaryotic cell into at least the cytoplasm of the cell using a genus of carrier peptide fragments comprising the amino acid sequence of SEQ ID No: 1: KKRTLRKSNRKKR (with the lysine residue at the 12th position being a D-form and the other amino acid residues being L-forms) with addition of any amino acid sequences upstream or downstream of this sequence. However, the specification only discloses a single species of the specific carrier peptide fragment consisting of the claimed amino acid sequence and forms that has cell membrane permeation ability. Thus, the specification fails to describe the genus of methods.
ACTUAL REDUCTION TO PRACTICE
Accordingly, Applicant did not demonstrate a reduction to practice of a genus of carrier peptide fragments comprising the claimed amino acid sequence of SEQ ID No: 1 (with the lysine at the 12th position being D-form and the other residues being L-forms) with addition of any other amino acid sequences upstream or downstream of the sequence. Since the specification only discloses and provides guidance for a single species of the specific carrier peptide fragment consisting of the claimed amino acid sequence and forms that has cell membrane permeation ability and is used to transfer a target foreign substance into a cell, the absence of working examples necessitates further experimentation. Therefore, the specification does not provide sufficient guidance on how to use the claimed genus of methods.
STATE OF THE ART & QUANTITY OF EXPERIMENTATION
In fact, the state of the art teaches that a method for transferring a target foreign substance into a cell by using a carrier peptide fragment comprising the claimed amino acid sequence and forms with addition of any amino acid sequences upstream or downstream of the sequence is not a highly successful technique or has highly variable results.
Prior art Goyal et al., (J Biol Chem. 2006;281(35):25223-25230) discloses a unique nuclear and nucleolar localization signal of LIM Kinase 2 “KKRTLRKNDRKKR” motif (that is similar to the instantly claimed sequence of KKRTLRKSNRKKR in instant SEQ ID NO: 1) and teaches “After fusing this motif to enhanced green fluorescent protein, the fusion protein localized exclusively in the nucleus and nucleolus” (e.g., abstract). However, Goyal further teaches “LIMK1 and LIMK2 are localized predominantly in the cytoplasm” (p. 25223, right col, para 2. It is noted that LIMK2 comprises the motif at amino acids 491-503 (abstract), i.e., the motif in LIMK2 cannot localize the full-length LIMK2 in the nucleus and nucleolus, as distinct from the motif-EGFP fusion protein), indicating that adding any amino acid sequences upstream or downstream of the motif (such as in the full-length LIMK2 protein) would likely compromise its function (such as the nuclear and nucleolar localization ability). Accordingly, Goyal evidences that making and using the claimed carrier peptide fragments, that comprise the claimed sequence and form with addition of any amino acid sequences upstream or downstream of the sequence, for transferring a foreign substance into a cell, was not well established.
Since the state of the art did not provide guidance for transferring a foreign substance into a eukaryotic cell by using a carrier peptide fragment comprising the claimed amino acid sequence and forms with addition of any amino acid sequences upstream or downstream of the sequence encompassed by the instant invention, it is incumbent upon the instant specification to do so. The physiological art is recognized as unpredictable (MPEP 2164.03). As set forth in In re Fisher, 166 USPQ 18 (CCPA 1970), compliance with 35 USC 112, first paragraph requires: “That scope of claims must bear a reasonable correlation to scope of enablement provided by specification to persons of ordinary skill in the art; … in cases involving unpredictable factors, such as most chemical reactions and physiological activity, scope of enablement varies inversely with degree of unpredictability of factors involved.” Moreover, the courts have also stated that reasonable correlation must exist between scope of exclusive right to patent application and scope of enablement set forth in the patent application (27 USPQ2d 1662 Ex parte Maize!.). In view of the foregoing, due to the lack of sufficient guidance provided by the specification regarding the issues set forth above, the state of the relevant art, and the breadth of the claims, it would have required undue experimentation for one skilled in the art to use the instant broadly claimed invention.
CONCLUSION
In conclusion, since the art teaches that the method for transferring a foreign substance into a eukaryotic cell by using a carrier peptide fragment comprising the claimed amino acid sequence and forms with addition of any amino acid sequences upstream or downstream of the sequence is prone to influence by multiple factors, and is highly unpredictable, and the specification does not provide ample guidance, one would be burdened with undue experimentation to use the claimed invention for transferring a foreign substance into a eukaryotic cell by using the claimed genus of carrier peptide fragments.
In conclusion, given the breadth of the claims and the limited scope of the specification, an undue quantity of experimentation is required to use the invention beyond the scope of a method for transferring a target foreign substance from outside a eukaryotic cell into at least the cytoplasm of the cell, the method comprising the steps of (1) preparing a construct, and (2) supplying the construct into a sample including the eukaryotic cell, wherein the construct comprises a carrier peptide fragment and a foreign substance that is bonded to the N-terminus and/or C-terminus of the carrier peptide fragment, wherein the carrier peptide fragment consists of the amino acid sequence of SEQ ID No: 1: KKRTLRKSNRKKR, wherein the lysine residue at the 12th position from the N-terminus of the amino acid sequence is a D-form and the other amino acid residues are L-forms.
Double Patenting Rejections
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of US Patent Nos. 12,617,817 (‘817) or 12,392,770 (‘770) in view of Shaik et al., (Oncotarget. 2018; 9(70): 33249-33257). Although the claims at issue are not identical, they are not patentably distinct from each other.
Patent claims of ‘817 recite a method of introducing a foreign substance of interest into at least cytoplasm of eukaryotic cells from outside the cells, the method comprising: (1) a step of preparing a foreign substance introduction construct including a carrier peptide fragment composed of the amino acid sequence below (SEQ ID NO: 1) KKRTLRKSNRKKR (the exact same sequence as instantly claimed in instant claim 1) and the foreign substance of interest linked to the N-terminal and/or C-terminal side of the carrier peptide fragment; (2) a step of supplying the foreign substance introduction construct to a sample containing a target eukaryotic cell (reference claim 1 related to instant claim 5), wherein the target eukaryotic cell into which the foreign substance introduction construct is introduced is a human or non-human mammalian cell (reference claim 5, related to instant claim 6), a foreign substance introduction construct prepared for introducing a foreign substance of interest into at least cytoplasm of eukaryotic cells from outside the cells, the foreign substance introduction construct comprising: a carrier peptide fragment composed of KKRTLRKSNRKKR (SEQ ID NO: 1), and the foreign substance of interest linked to the N-terminal and/or C-terminal side of the carrier peptide fragment (reference claim 6, related to instant claims 1-2 and 4), wherein the foreign substance is any organic compound selected from the group consisting of polypeptides, nucleic acids, dyes, and drugs (reference clam 7, related to instant claim 3).
Patent claims of ‘770 recite a method for introducing a foreign substance of interest from outside a eukaryotic cell into at least a cytoplasm of the cell, the method comprising: a step of preparing a foreign substance introduction construct that has a carrier peptide fragment comprising either of the following amino acid sequences: (SEQ ID NO: 1) KKRTLRKSNRKKRWPC (the first 13 amino acids being the exact same sequence as instantly claimed in instant claim 1) and the foreign substance of interest bonded to an N-terminal side and/or C-terminal side of the carrier peptide fragment; a step of supplying the foreign substance introduction construct into a sample that contains a target eukaryotic cell (reference claim 1 related to instant claim 5), wherein the eukaryotic cell that is the target for the introduction of the foreign substance introduction construct is a human cell or a cell from a nonhuman mammal (reference claim 5, related to instant claim 6), a foreign substance introduction construct for introducing a foreign substance of interest from outside a eukaryotic cell into at least the cytoplasm of the cell, comprising: a carrier peptide fragment comprising either of the following amino acid sequences: (SEQ ID NO: 1) KKRTLRKSNRKKRWPC and the foreign substance of interest bonded to the N-terminal side and/or the C-terminal side of the carrier peptide fragment (reference claim 6, related to instant claims 1-2 and 4), wherein the foreign substance is any organic compound selected from the group consisting of polypeptides, nucleic acids, dyes, and drugs (reference clam 7, related to instant claim 3), wherein the foreign substance is located at the C-terminal side of the carrier peptide fragment (reference claim 8, related to instant claim 4).
One of ordinary skill in the art would have immediately expected that the amino acid residues in the carrier peptide fragment in the patents would likely be L-forms since that is the natural form of amino acids in vivo.
However, patent claims are silent on the limitation that the lysine residue at the 12th position from the N-terminus of the amino acid sequence is a D-form and the other amino acid residues are L-forms.
Shaik teaches an E2F1 inhibitory peptide coupled to penetratin (PEP) increase its uptake into cells (e.g., abstract), thus teaches a construct comprising a carrier peptide fragment (i.e., the penetratin) and a foreign substance (an E2F1 inhibitory peptide) that is bonded to the carrier peptide fragment. Shaik teaches the E2F inhibiting L-enantiomeric penetratin peptide was found to be unstable in serum and acknowledges that there are a vast array of modifications for protecting biologically active peptides from enzymatic degradation in serum, such as N-terminal acetylation and incorporation of non-natural amino acids such as D- amino acids, and substitution of L- by D-amino acids is a well-established strategy to increase the stability of a peptide (p. 33250, left col, para 4 and p. 33254, para 1). Shaik teaches a new peptide form, D-Arg PEP was generated by substituting L-arginine with D-arginine in the L- PEP peptide sequence (p. 33250, left col, para 4) and teaches the D-Arg penetratin peptide (D-Arg PEP) was more stable than the L- form and was more cytotoxic as compared to the L-Arg PEP when tested against the human castrate resistant cell lines (e.g., abstract). Thus, Shaik teaches even a single substitution of an L- by D-amino acid (e.g., substituting L-arginine with D-arginine) is sufficient to increase the stability and the function of the penetratin peptide, evidenced by the increased cytotoxicity in cancer cells.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to have modified the method and the construct recited in the patent claims of ‘817 or ‘770, by combining a single substitution of an L- by D-amino acid in the carrier peptide fragment as suggested by Shaik with a reasonable expectation of success. Since Shaik teaches even a single substitution of an L- by D-amino acid (e.g., substituting an L-arginine with a D-arginine) is sufficient to increase the stability and the function of the penetratin peptide evidenced by the increased cytotoxicity in cancer cells (e.g., abstract), one of ordinary skill in the art would have had a reason to combine a single substitution of an L- by D-amino acid in the carrier peptide fragment as suggested by Shaik in order to improve the stability and the function of the carrier peptide fragment.
Furthermore, in regard to the specific lysine residue at the 12th position from the N-terminus of the amino acid sequence being a D-form, it is noted that the patent claims recite a carrier peptide fragment merely having 13 amino acids or 16 amino acids. Therefore, one of ordinary skill in the art would have immediately envisioned the taught option of substituting the lysine residue at the 12th position from the N-terminus of the amino acid sequence from an L-form to a D-form, among the limited genus of options (13 options or 16 options) as suggested by Shaik. See MPEP 2131.02 (III).
Since the instant application claims are obvious over cited patent claims, in view of Shaik, said claims are not patentably distinct.
Provisional Double Patenting Rejections
Claims 1-6 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over copending claims 1-10 of copending Application No. 18/876,605 (‘605). Although the claims at issue are not identical, they are not patentably distinct from each other.
Copending claims of ‘605 recite a carrier peptide fragment comprising the following amino acid sequence: RKKRNSKRLTRKK (copending claim 1, the exact same sequence in a reverse order as instantly claimed KKRTLRKSNRKKR in instant claim 1), wherein a D-lysine residue is included as a lysine residue of the amino acid sequence (copending claim 3, related to instant claim 1), a construct comprising the carrier peptide fragment according to claim 1; and a foreign substance that is bonded to an N-terminus and/or a C-terminus of the carrier peptide fragment (copending claim 4, related to instant claim 2), wherein the foreign substance is at least one kind of organic compound selected from the group consisting of a polypeptide, a nucleic acid, a dye, and a drug (copending claim 5, related to instant claim 3), wherein the foreign substance is disposed on the C-terminus of the carrier peptide fragment (copending claim 6, related to instant claim 4), a method for transferring a target foreign substance from outside a eukaryotic cell into at least a cytoplasm of the cell, the method comprising the steps of: (1) preparing a construct including the carrier peptide fragment according to claim 1, and the target foreign substance that is bonded to an N-terminus and/or a C-terminus of the carrier peptide fragment; and (2) supplying the construct into a sample including a target eukaryotic cell (copending claim 7, related to instant claim 5), wherein the eukaryotic cell to which the construct is to be transferred is a human or nonhuman mammalian cell (copending claim 10, related to instant claim 6).
However, although copending claim 3 recites a D-lysine residue is included as a lysine residue of the amino acid sequence indicating that the other amino acid residues are L-forms, copending claims do not specifically recite the lysine residue at the 12th position from the N-terminus of the amino acid sequence is a D-form.
Nevertheless, since the copending claims recite a carrier peptide fragment comprising the amino acid sequence that merely has 5 lysine residues, one of ordinary skill in the art would have immediately envisioned the taught option of including the lysine residue at the 12th position from the N-terminus of the amino acid sequence being D-form, among the limited genus of options (5 options) as taught by copending claims. See MPEP 2131.02 (III).
Since the instant application claims are obvious over cited application claims, said claims are not patentably distinct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims in the copending application have not in fact been patented.
Conclusion
No claims are allowed.
Examiner Contact Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jianjian Zhu whose telephone number is (571)272-0956. The examiner can normally be reached M - F 8:30AM - 4PM (EST).
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/JIANJIAN ZHU/Examiner, Art Unit 1631
