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 .
This is the First Office Action on the Merits of US18/029,174 filed on 03/29/2023 which is a 371 of PCT/EP2021/076844 filed on 09/29/2021 which claims US priority benefit of US Provisional 63/085,771 filed on 09/30/2020. The Filing Receipt received on 10/11/2023 is controlling.
The Applicants’ Amendment to the Claims filed on 12/01/2025 is entered.
Claims 2-3, 5-6, are cancelled.
Claims 1, 4, and 7-28 are pending.
Claims 4 and 9-28 are withdrawn.
Claims 1 and 7-8 are under examination in this office action.
Election/Restrictions
Applicant’s election without traverse of invention Group I (i.e., claims 1 and 7-8) in the reply filed on 12/01/2025 is acknowledged.
Claims 4 and 9-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/01/2025.
Information Disclosure Statement
The IDS statements filed on 03/29/23, 05/25/2023, and 10/10/2025 have been considered by the examiner.
Specification
The disclosure is objected to because of the following informalities: A heading for “Brief Description of the Drawings” should be included in page 40.
Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informalities: For improved clarity, the term “selected from the group of” in line 4 should be amended to recite “selected from the group consisting of”.
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.
Claims 1 and 7-8 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites the limitation "wherein at least 50% of said amino acids" in line 3. There is insufficient antecedent basis for this limitation in the claim. The antecedent basis appears to be found in the term “a source of autophagy inhibiting amino acids“ in line 3. However, this phrase recites a source of autophagy inhibiting amino acids. . It appears reciting “said source of autophagy inhibiting amino acids” would be remedial. Regarding present claims, it is unclear if the 50% parameter is intended to mean that 50% of the total amino acids found in the source are selected from the group of amino acids listed in the claim. For example, a source could be a peptide containing all glycine residues which could be interpreted to meet the limitation of the claim but which would not necessarily result in the cells being provided with a composition that is 50% of total amino acids being selected from the list of amino acid residues recited in the claims. Alternatively, the source could be a mixture of different peptides having a mix of amino acids listed in the claim. Thus, as written, it is unclear what composition is required to be provided to the cells. During examination claims must be given their broadest reasonable interpretation in light of the specification but without reading limitations into the claim. Thus present claims are construed to read on the broader interpretation where “a source” which may read on a single peptide or a composition of single amino acids, where at least 50% amino acid residues are selected from the group of alanine (in one letter code: A), glutamine (Q), glycine (G), valine (V), leucine (L), isoleucine (I), proline (P) and arginine (R). This interpretation does not require that the total potential amino acids provided to the cell is 50% of total.
Claims 7-8 are indefinite as they depend from claim 1 and are not remedial.
Also, claims 7-8 are indefinite because each of claims 7-8 lack sufficient antecedent basis for the term “said amino acid” in claims 7-8 for the same reasoning provided for claim 1. It appears reciting “said source of autophagy inhibiting amino acids” would be remedial.
Also, regarding claims 7-8, the term “said group of autophagy inhibiting amino acids” lacks sufficient antecedent basis because claim 1 does not actually recite the term “a group of autophagy inhibiting amino acids”. Claim 1 recites “a source of autophagy inhibiting amino acids“ but does not actually specify that the listing of amino acids in claim 1 is “said group of autophagy inhibiting amino acids”. For purpose of examination claims 7-8 are being construed to mean that any single source of autophagy inhibiting amino acids provided to the cells must contain an amino acid from the group consisting of: alanine (A), glutamine (Q), glycine (G), valine (V), leucine (L), isoleucine (I), proline (P) and arginine (R). Further, if the method discloses providing a single amino acid from this list, the single amino acid meets the limitation that the source comprises 100% of an autophagy inhibiting amino acid.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(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.
Claims 1 and 7-8 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 of providing specific cells recited in the instant FIGs and Examples (such as endothelial cells to assay cytoskeleton organization or human U937 cells to assay mTOR activity) with a source of autophagy inhibiting amino acids being an AQGV peptide or salt of an organic acid selected from maleic acid, acetic acid, tartaric acid, and citric acid, thereof (i.e., SEQ ID NO: 5), for reducing cytoskeleton organization or mTOR does not reasonably provide enablement for the broad embodiments encompassed by the present claims. 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 following factors have been considered in the analysis of enablement: (1) the
nature of the invention, (2) the breadth of the claims, (3) the state of the prior art, (4) the level of one of ordinary skill, (5) the level of predictability in the art, (6) the amount of direction provided by the inventor, (7) the existence of working examples, (8) the quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed.Cir. 1988).
The nature of the invention: The invention is drawn to a method for reducing p38 MAPK kinase activity, for reducing PI3/AKT/mTOR activity, or for reducing cytoskeleton reorganization comprising providing cells with a source of amino acids having at least 50% of amino acids being an alanine, glutamine, glycine, valine, leucine, isoleucine, proline or arginine. The 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).
(2) The breadth of the claims: The claims are broad to any type of cell including cells within a human patient and any source of autophagy inhibiting amino acids having at least 50% of amino acids being an alanine, glutamine, glycine, valine, leucine, isoleucine, proline or arginine.
(3) The state of the prior art: A review of the patent and non-patent literature indicates that methods of providing cells with autophagy inhibiting amino acids and peptides consisting of autophagy inhibiting amino acids were routinely practiced before the effective filing date of the presently claimed invention. See prior art rejections below. However, using these methods to achieve the intended use recited in claim 1 for reducing p38 MAPK kinase activity, for reducing PI3/AKT/mTOR activity, or for reducing cytoskeleton reorganization appears to be cell-specific and unpredictable. For example, Kahn et al discloses that glutamine (i.e., an autophagy inhibiting amino acid) effects on cellular AKT/mTOR activity cell-specific and context-specific. (See Abstract; page 2040, right col, para 1; Fig7, page 2050). In addition, Follo et al teach a method of providing cancer cells with an autophagy inhibiting amino acid being proline and monitoring the effect on mTORC1 activity. (See Follo et al, Cell Communications and Signaling 2019 Vol 17, pages 1-18). Also, Son et al shows that leucine results in acetyl-CoA which promotes mTORC1 activity through EP300-mediated acetylation of Raptor, an mTORC1 regulator. Son et al disclose that this pathway is cell-type specific and context-specific. (See Son et al Cell Metabolism 2019 Vol 29, pages 192-201; Abstract, entire document).
(4) The level of one of ordinary skill: The relative skill of those in the art is high,
generally that of Ph.D research scientist.
(5) The level of predictability in the art: The level of predictability is considered variable as evident in the prior art discussed above and is not considered to provide sufficient enablement to practice the claimed invention. For example, Son et al shows it was unpredictable before the effective filing date of the claimed invention whether a given amino acid listed in the present claims would effect mTOR activity. Son et al discloses that “Leu treatment failed to rescue mTORC1 activity in AA-starved, AUH knockdown cell”. Further, Son et al state that they further treated starved cells with isoleucine, valine, showing valine had no effect, and only high concentrations of isoleucine could rescue mTORC1 activity in AA-starved cells.
(6) The amount of direction provided by the inventor: The instant specification shows a method of providing specific cells recited in the instant FIGs and Examples (such as endothelial cells to assay cytoskeleton organization or human U937 cells to assay mTOR activity) with a source of autophagy inhibiting amino acids being a specific peptide salt, with a preferred embodiment of an AQGV peptide or salt of an organic acid selected from maleic acid, acetic acid, tartaric acid, and citric acid, thereof (i.e., SEQ ID NO: 5), for reducing cytoskeleton organization or mTOR activity. The specification lists 32 examples of such peptides. (See pages 61-67).
(7) The existence of working examples: The working embodiment in the instant
application describes a method of providing human derived peripheral blood monocytes (“as a prototype cell-system for FPR-expression”). (See page 59.) These cell were provided with the peptide AQGV. Results are shown in Fig4.
However, the working example(s) do not encompass the breadth of the present claims using any cell type and any source of autophagy inhibiting amino acids. While the MPEP 2164.02 states the specification need not contain an example if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. In re Borkowski, 422 F.2d 904, 908, 164 USPQ 642, 645 (CCPA 1970), the lack of a working example, however, is a factor to be considered, especially in a case involving an unpredictable and undeveloped art.
(8) The quantity of experimentation needed to make or use the invention: In view of unpredictable nature of embodiments encompassed by the breadth of the present claims, as evidenced by the cited references, without further guidance, one of skill in the art would have to practice a substantial amount of trial and error experimentation, an amount considered undue and not routine, to practice the instantly claimed invention.
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim interpretation regarding claims 1 and 7-8: Claims are drawn to a method the active method step of providing cells with a source of autophagy inhibiting amino acids, wherein at least 50% of said amino acids are selected from the group of alanine (A), glutamine (Q), glycine (G), valine (V), leucine (L), isoleucine (I), proline (P) and arginine (R). The intended use “for reducing p38 MAPK kinase activity, for reducing PI3K/AKT/mTOR activity, or for reducing cytoskeleton reorganization” is not generally provided weight for purpose of applying prior art especially because this intended use language in the preamble is not further connected to active method step in the body of the claim. Further, regarding the limitations of amino acids being 50%, 75%, and 100%, it is noted that the claim is drawn to providing a source. Such source may be a single type of autophagy inhibiting amino acid. Providing a single type of such amino acid to the cell meets the limitation of amino acids being 50%, 75%, and 100%.
Claims 1 and 7-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 2008/171094 to Benner et al (published July 17, 2008).
Regarding claims 1 and 7-8 Benner et al describes (see Examples, Figs. 7-11) providing cells by intraperitoneal injection a source of autophagy inhibiting amino acids, specifically the peptides: LAGV, AQGV, VLPALPQ or LQGV. Benner et al show providing these peptides had beneficial activity on the imiquimod induced skin lesions in mice, an animal model for burn patients; also salts of the said peptides such as salts of maleic acid, tartaric acid and citric acid are disclosed (see para 0070). Regarding the limitations regarding amino acid composition of at least 50% (claim 1), 75% (claim 7) and 100% (claim 8), these peptide sources LAGV, AQGV, VLPALPQ or LQGV consist solely of amino acids selected from the group of alanine (A), glutamine (Q), glycine (G), valine (V), leucine (L), isoleucine (I), proline (P) and arginine (R).
Thus, Benner et al anticipates claims 1 and 7-8 as presently written.
Claims 1 and 7-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Follo et al (Cell Communications and Signaling 2019 Vol 17, pages 1-18).
Regarding claims 1 and 7-8, Follo et al teach a method of providing cancer cells with an autophagy inhibiting amino acid being proline and monitoring the effect on mTORC1 activity. See Fig9 just below.
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Thus, Follo et al anticipates claims 1 and 7-8 as presently written.
Claims 1 and 7-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Son et al (Cell Metabolism 2019 Vol 29, pages 192-201).
Regarding claims 1 and 7-8, Son et al shows that leucine results in acetyl-CoA which promotes mTORC1 activity through EP300-mediated acetylation of Raptor, an mTORC1 regulator. Son et al disclose that this pathway is cell-type specific and context-specific. (See Abstract, entire document). Son et al teach that “Leu treatment failed to rescue mTORC1 activity in AA-starved, AUH knockdown cell”. Further, they state that they further treated starved cells with isoleucine, or valine, showing valine had no effect, and only high concentrations of isoleucine could rescue mTORC1 activity in AA-starved cells.
Thus, Son et al anticipates claims 1 and 7-8 as presently written.
Double Patenting
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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1, and 7-8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 30-55 of copending Application No. 18/548,845 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because instant claims are anticipated by copending claims.
Regarding instant claims 1, and 7-8, copending claim 34 recites providing a neutrophil cell with a source which is a dipeptide AQ. A dipeptide AQ meets the limitation of a source comprising 100% autophagy inhibiting amino acids. Thus copending claim 34 anticipates instant claims 1 and 7-8.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, and 7-8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 61 and 63 of copending Application No. 17/639018 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because instant claims are rendered obvious over the combination of copending claims 61 and 63.
Regarding instant claims 1, and 7-8, copending claim 63 recites a method of modifying vascular permeability in a subject by administering the pharmaceutical of claim 58. Claim 61 depends from claim 58 and recites the peptide source of LQGV which has 100% autophagy inhibiting amino acids.
It would have been prima facie obvious to use the pharmaceutical composition of copending claim 61 in the method of copending claim 63 because each of these claims depends from the same base claim 58.
Thus the combination of copending claims 61 and 63 renders obvious instant claims 1 and 7-8.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
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CATHERINE S. HIBBERT
Primary Examiner
Art Unit 1658
/CATHERINE S HIBBERT/Primary Examiner, Art Unit 1658