DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application filed 08/07/2023 is a National Stage entry of PCT/US22/15480 , International Filing Date: 02/07/2022. PCT/US22/15480 Claims Priority from Provisional Application 63278740 , filed 11/12/2021. PCT/US22/15480 Claims Priority from Provisional Application 63146321 , filed 02/05/2021.
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/21/2023 is in compliance with the
provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by
the examiner.
Claim Interpretation
For the purpose of applying prior art, the claim scope has been interpreted as per the guidance set forth in MPEP § 2111.
For claim 1, regarding the scope of “reducing the risk of a sepsis-induced vascular leak, tissue edema or organ dysfunction in a subject comprising administering an effective amount of a composition”, t is noted that the instant specification does not define “reduce the risk”. In the absence of an express intent to impart a novel meaning to the claim terms, the words are presumed to take on the ordinary and customary meanings attributed to them by those of ordinary skill in the art. The ordinary and customary meaning of a term may be evidenced by a variety of sources, including the words of the claims themselves, the specification, drawings, and prior art. However, the best source for determining the meaning of a claim term is the specification as set forth in MPEP § 2111.01 (III). As noted, for example in Fig 17 A-G, the Examiner interprets “reducing the risk” to encompass “reduce severity”. Thereafter, in claims 2-17, 19 and 20, the Examiner interprets “reducing the risk” as “reduce severity”, in determining the meaning of the claim term as set forth in the Figures.
Regarding claims 1-17, 19 and 20, the preamble is read in the context of the claim (see MPEP § 2112.02). The Examiner interprets the method claims as reducing the severity, in a subject population, who are not presented with the associated symptoms of sepsis (as recited in claims 1-8, 19), and heart attack (as recited in claims 9-17, 20) at the time when the method is practiced. Therefore, the subject population is any population absent the aforementioned symptoms.
Regarding claims 1, 9, 19 and 20, the disjunctive conjunction “or” is interpreted by the examiner as presenting alternatives. For example, in claim 1, “reducing the risk” is directed to “sepsis-induced vascular leak” or to “tissue edema” or to “organ dysfunction” as alternatives. Claim 1 is not interpreted by the Examiner as “sepsis-induced vascular leak” or “sepsis-induced tissue edema” or “sepsis-induced organ dysfunction”.
The interpretation of “or” in claim 1, is extended to claims 9, 19 and 20.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-17, 19 and 20 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.
The claimed invention is directed to a method of reducing risk of: 1) sepsis-induced vascular leak, tissue edema or organ dysfunction as recited in claims 1-8 and 19, 2) heart attack-induced cardiac dysfunction, atherosclerosis, inflammatory bowel disease or diabetes-induced cardiomyopathy, as recited in claims 9-17 and 20 -in a subject, comprising administering Lipocalin 10 (Lcn10; SEQ ID NO: 1), truncated Lipocalin 10 (SEQ ID NO: 2), Lcn10 expressing vectors for SEQ ID NO: 1 or SEQ ID NO: 2 and combinations thereof. The specification reduces to practice experiments to teach reducing the risk, comprising administering Lipocalin 10 (Lcn10; SEQ ID NO: 1) and Lcn10 expressing vectors for SEQ ID NO: 1 (Fig 8, Fig 10, Fig 11, Fig 17, Fid 20, Fig 21, Fig 23). The specification does not teach administering truncated Lipocalin 10 (SEQ ID NO: 2), Lcn10 expressing vectors for SEQ ID NO: 2 or combinations comprising SEQ ID NO: 2 to achieve the desired result.
While the general knowledge and level of skill in the art for peptide amino acids is evident, this knowledge and level of skill does not supplement the omitted description because specific, not general guidance is needed for the Lcn10 truncate, Lcn10 expressing vectors for SEQ ID NO: 2 or combinations comprising SEQ ID NO: 2 to achieve the desired result.
There is a presumption that an adequate written description of the claimed invention is present when the application is filed. In re Wertheim, 541 F.2d 257, 263, 191 USPQ 90, 97 (CCPA 1976) ("[W]e are of the opinion that the PTO has the initial burden of presenting evidence or reasons why persons skilled in the art would not recognize in the disclosure a description of the invention defined by the claims."). However, issues of adequate written description may arise even for original claims, for example, when an aspect of the claimed invention has not been described with sufficient particularity such that one skilled in the art would recognize that the inventor had possession of the claimed invention at the time of filing. 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 (see MPEP 2163 I(A)).
Possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing that the invention was "ready for patenting" such as by the disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the inventor was in possession of the claimed invention. See, e.g., Pfaff v. Wells Elecs., Inc., 525 U.S. 55, 68, 119 S.Ct. 304, 312, 48 USPQ2d 1641, 1647 (1998); Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406; Amgen, Inc. v. Chugai Pharm., 927 F.2d 1200, 1206, 18 USPQ2d 1016, 1021 (Fed. Cir. 1991).
In the instant case, one would only conclude that Applicant was in possession of a method of reducing the risk, using Lipocalin 10 (SEQ ID NO: 1) and Lipocalin 10-expressing vectors and not the truncate or vector expressing the truncate or combinations with the truncate as claimed.
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.
Claims 1-17, 19 and 20 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.
Regarding claims 1 and 19, the limitation “reducing the risk of sepsis-induced vascular leak, tissue edema or organ dysfunction” can be interpreted as a list of potential alternatives which can vary and ambiguity arises. Does the Applicant mean: reducing the risk of sepsis-induced i) vascular leak ii) tissue edema or iii) organ dysfunction or does the applicant mean sepsis-induced vascular leak or tissue edema or organ dysfunction. Claims 1 and 19 are indefinite as it is unclear what the limitation is referring to. For examination, the claim will be interpreted as the latter.
Regarding claim 9 and 20, the limitation “reducing the risk of a heart attack-induced cardiac dysfunction, atherosclerosis, inflammatory bowel disease or diabetes-induced cardiomyopathy” can be interpreted as a list of potential alternatives which can vary and ambiguity arises. Does the Applicant mean: reducing the risk of a heart attack-induced i) cardiac dysfunction ii) atherosclerosis or iii) inflammatory bowel disease iv) diabetes-induced cardiomyopathy or does the applicant mean heart attack-induced cardiac dysfunction or atherosclerosis or inflammatory bowel disease or diabetes-induced cardiomyopathy. Claims 9 and 20 are indefinite as it is unclear what the limitation is referring to. For examination, the claim will be interpreted as the latter.
Claims 2-8 which depend on claim 1 and claims 10 to 17 which depend on claim 9 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as these claims incorporate by dependency the indefiniteness of claims 1 and 9.
Claim Rejections - 35 USC § 101
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.
Claim 18 is rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon (natural product) without significantly more. The claim recites the judicial exception of SEQ ID NO: 2. This judicial exception is not integrated into a practical application because the claim is drafted such that there is no difference in substance from the sequence claim of SEQ ID NO: 2, to the naturally occurring human lipocalin 10 protein (LCN10_HUMAN). The claim does not include additional elements that are sufficient to amount to significantly more than the judicial exception because the additional claim elements do not integrate the judicial exception into something more than the judicial exception. See the following analysis:
Step 1: Is the claim to a process, machine, manufacture or composition of matter?
Yes, the claim is directed to a composition of matter.
Step 2A: Is the claim directed to a law of nature, a natural phenomenon (product of nature) or
abstract idea?
Prong One: Does the claim recite an abstract idea, law of nature or natural phenomenon? Yes,
the claim recites an amino acid sequence. Under the broadest reasonable interpretation, the claimed
sequence SEQ ID NO: 2 is the sequence of LCN10_HUMAN protein that is naturally occurring.
Prong Two: Does the claim recite additional elements that integrate the judicial exception into a
practical application? No, the additional elements in the claim do not integrate the judicial exceptions
into a practical application. The claim is directed only to the amino acid sequence and to the function
incorporated by the sequence.
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.
Claims 1-5 and 9-14 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Shedlock, Devon et al., hereinafter Devon (WO2019046815A1; published 2019-03-07) (reference provided in the IDS).
Devon teaches methods to express an exogenous sequence (e.g. a chimeric antigen receptor or therapeutic protein) in primitive HSCs (hematopoietic stem cells), HSCs, and/or HSC descendent cells [0106]. Therapeutic proteins of the disclosure include secreted proteins. Devon teaches therapeutic proteins listed in Table 1 [0398]. In Table 1, Devon teaches Lipocalin 10 (gene name LCN10), SEQ ID NO: 7741 which has 100% sequence identity to SEQ ID NO: 1 of the instant application. Devon teaches, in a therapeutic context, the therapeutic protein is a human protein, including a secreted human protein. When expressed or secreted by immune or immune precursor cells of the disclosure, the combination comprising the immune or immune precursor cell and the therapeutic protein secreted therefrom may be considered a monotherapy. However, the immune or immune precursor cells of the disclosure
may be administered as a combination therapy with a second agent [0397]. Primitive HSCs produced by the methods of the disclosure may be therapeutically-effective when administered as a single dose [0105]. Devon teaches that modified T cells, derived from modified HSCs persists in a patient as a stable population to prevent potential relapse [0108]. As noted, in certain embodiments of the methods of Devon, the subject has a disease or disorder and the plurality of therapeutic immune cells or immune precursor cells improves a sign or symptom of the disease or disorder, optionally by providing a therapeutic protein systemically or locally within the subject [0401]. Devon teaches that therapeutic secreted proteins may be used as monotherapy or in combination with another therapy in the treatment or prevention of any disease or disorder [0401].
Claim 1 is directed to reducing the risk of sepsis-induced vascular leak or tissue edema or organ
dysfunction in a subject, not presented with the disease at the time the method is practiced (see Claim interpretation section). The method comprises administering a composition “selected from the group consisting of Lipocalin 10 (SEQ ID NO: 1), a truncated Lipocalin 10 (Lcn10) protein having the amino acid sequence SEQ ID NO: 2, Lcn10- expressing vectors for full length/truncated Lcn10, and combinations thereof” which is a Markush grouping of a closed set of alternatives (MPEP § 2173.05(h)).
Devon specifically teaches therapeutic protein SEQ ID NO: 7741, Lipocalin 10 (see Table 1), which has 100% sequence identity to SEQ ID NO: 1 in the instant application. Devon teaches therapeutic proteins in the treatment or prevention of disease [0401]. Devon teaches that T cells derived from modified HSCs, modified to express the therapeutic protein, persists in a patient as a stable population to prevent potential relapse [0108].
Claims 2-5 are directed to the method of claim 1 wherein the method reduces the risk of tissue edema, organ dysfunction and sepsis-induced vascular leak. The teachings of Devon anticipate claims 1-5.
Claim 9 is directed to reducing the risk of heart attack-induced cardiac dysfunction or atherosclerosis or inflammatory bowel disease or diabetes-induced cardiomyopathy
in a subject, that is not presented with the disease at the time the method is practiced (see Claim interpretation section).
Claims 10-14 are directed to the method of claim 9 wherein the method reduces the risk of heart attack-induced cardiac dysfunction as recited in claim 10, atherosclerosis as recited in claim 11, inflammatory bowel disease as recited in claim 12 and diabetes-induced cardiomyopathy as recited in claim 13.
Claim 14 is directed to the method of claim 9 wherein the subject is administered SEQ ID NO: 1.
Devon teaches therapeutic protein Lipocalin 10, which has 100% sequence identity to SEQ ID NO: 1 (see SEQ ID NO: 7741; Table 1 in Devon). Devon teaches therapeutic proteins in the treatment or prevention of disease [0401]. Devon teaches that T cells derived from modified HSCs, modified to express the therapeutic protein, persists in a patient as a stable population to prevent potential relapse [0108]. In the embodiments of methods taught in Devon, the subject has a disease or disorder and the plurality of therapeutic immune cells or immune precursor cells improves a sign or symptom of the disease or disorder, optionally by providing a therapeutic protein systemically or locally within the subject [0401]. Devon teaches that therapeutic secreted proteins may be used as monotherapy or in combination with another therapy in the treatment or prevention of any disease or disorder [0401].
Regarding claims 1-4 and 9-13, the claim limitation “reducing the risk” is interpreted by the examiner as intended use. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. Shoes by Firebug LLC v. Stride Rite Children’s Grp., LLC, 962 F.3d 1362, 2020 USPQ2d 10701 (Fed. Cir. 2020) (see MPEP § 2111. 02 (II)). As previously noted, where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). (See MPEP § 2112.01 (I)).
Therefore, the disclosure of Devon anticipates claims 1-5 and 9-14.
Claim Rejections - 35 USC § 103
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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 7, 8, 16 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Shedlock, Devon et al., hereinafter Devon (WO2019046815A1; published 2019-03-07) in view of Fitzgerald, Steven et al., hereinafter Fitz (WO2006040574A2; published 20 April 2006) (references provided in the IDS).
Claims 8 and 17 are directed to administering Lipocalin 10 via vein injection in a subject.
Claims 7 and 16 are directed to a dosage of 50-200 ng/g body weight.
Devon teaches Lipocalin 10 therapeutic protein (SEQ ID NO: 7741) in the treatment or prevention of disease (see Table 1 [0401]). Devon teaches that in a therapeutic context, the therapeutic protein is a human protein, including a secreted human protein. When expressed or secreted by immune or immune precursor cells, the combination comprising the immune or immune precursor cell and the therapeutic protein secreted therefrom may be considered a monotherapy. In the embodiments of methods taught in Devon, the subject has a disease or disorder and the plurality of therapeutic immune cells or immune precursor cells improves a sign or symptom of the disease or disorder, optionally by providing a therapeutic protein systemically or locally within the subject [0401].
Devon does not teach a dosage of 50-200 ng/g body weight. Devon does not teach the method wherein the subject is administered with Lipocalin 10 via vein injection.
Fitz teaches lipocalin-like polypeptides of which INSP153 (SEQ ID NO: 30) is the closest homolog for Lipocalin 10 (see page 2; line 15 and page 7; line 28). Fitz teaches INSP153pred, INSP153, INSP153-SV1, INSP153-SV2, INSP153-SV3 polypeptides, INSP153-soll polypeptide; INSP153-sol2 polypeptide and INSP153-sol3 polypeptide and/or fragments thereof (e.g. fragments containing the lipocalin domain) useful in the diagnosis and/or treatment of diseases (see page 14, line 25). Fitz teaches pharmaceutical compositions comprising polypeptide, or a nucleic acid molecule, or a vector, or a host cell (see page 16, line 30). Fitz teaches that the pharmaceutical composition may be administered by “intravenous routes” (page 50, line 19) and “direct delivery accomplished by injection,....intravenously” (page 50, line 28). Fitz teaches that the precise effective amount for a human subject can be determined by routine experimentation and is within the judgement of the clinician. Generally, an effective dose will be from 0.01 mg/kg to 50 mg/kg, preferably 0.05 mg/kg to 10 mg/kg (page 49, line 24). Fitz explicitly teaches that since polypeptides may be broken down in the stomach, they are preferably administered parenterally (for instance intravenous, etc.) (page 53, line 23).
Obviousness can be established by combining or modifying the teachings of the prior art to
produce the claimed invention where there is some teaching, suggestion, or motivation to do so. In re Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) (discussing rationale underlying the motivation-suggestion-teaching test as a guard against using hindsight in an obviousness analysis).
Consequently, it would have been prima facie obvious to one of ordinary skill in the art before
the effective filing date of the claimed invention to administer SEQ ID NO: 1 taught in Devon, intravenously, and at the dose range, as taught by Fitz, to reduce the risk of disease. One motivated to do so would have a reasonable expectation of success, as polypeptides, breakdown in the stomach and therefore are preferably administered parenterally (see Fitz page 53, line 23). Thus, one would have recognized that applying the teaching of Devon to the method of Fitz would have yielded predictable results and improved the therapeutic availability of SEQ ID NO: 1 to reduce the risk of disease (See MPEP §2143 I(A)(D)).
Conclusion
No claim is allowed.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ARCHANA VARADARAJ whose telephone number is (571)272-2366. The examiner can normally be reached Monday-Friday 10:00am-5:00pm.
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/ARCHANA VARADARAJ/Examiner, Art Unit 1658
/LIANKO G GARYU/Supervisory Patent Examiner, Art Unit 1654