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 .
Claims 1-8 are pending.
Claims 9-19 have been cancelled.
Applicant’s election, without traverse, of Group I (claims 1-8) and of species SEQ ID NO: 1 and SEQ ID NO: 4 in the remarks dated 11/13/2024 is reacknowledged. Claim 6 remains withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species (SEQ ID NO: 3), there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/13/2024.
Claims 1 and 4-8 have been amended.
Claims 1-5 and 7-8 are under examination on the merits.
Information Disclosure Statement
The submission dated 02/23/2026 has been considered by the examiner.
Withdrawn Objections/Rejections
The objections to claims 4-5 are withdrawn as addressed by the corrective claim amendments dated 02/23/2026. The rejections under 35 USC 112(b) of claims 4-5 and 7 are withdrawn as addressed by the clarifying amendments dated 02/23/2026. The rejections of the claims under 35 USC §103 and for double patenting as presented in the previous office action dated 10/28/2025 are withdrawn and replaced with the rejections as presented in this Office Action to better account for the new claim scope resulting from the claim amendments dated (02/23/2026).
Maintained-Claim Interpretation
There is no closed definition of the recitation of distal administration (which is only mentioned 3 times in the instant specification). The clearest guidance given is the disclosure that “[i]n another aspect, the administration is systemic and is distal to the site of action,” (see for example, paragraph 0025 of the specification). Therefore, a recitation of distal administration is held to mean/encompass systemic administration such that prior art teaching systemic administration would anticipate/make obvious the limitation of distal administration.
The recitation of an effective amount is held to be an amount that induces exosome production, secretion, and/or function in a subject (as is consistent with the definition provided at paragraphs 0005, 0007, 0097, 0161, 0164, and 0168 of the instant specification, provided as exemplary citations).
Note that recitations of injury or injured tissue are being interpreted to encompass tissues impacted by altered blood flow and/or ischemia caused by conditions such as cardiomyopathy in the absence of a closed, preclusive definition. This is consistent with the specification as filed.
Claim Rejections - 35 USC § 112
New-35 USC § 112(a)-New Matter
Claims 5 is 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. This is a new matter rejection.
The examiner is unable to find support for the added limitation in claim 5, i.e., “ a constitutively active equivalent of each thereof having at least 95% sequence identity to SEQ ID NO: 4”. Applicant states that support for the amendments can be found at paragraphs 0009-0014, 0150, 0128, and 0199 (noting the final paragraph of the specification is paragraph 0194). However, this portion of the specification does not provide support for a constitutively active SDF-1. The only mention of a constitutively active SDF-1 relates to the non-elected SEQ ID NO:3, not the elected SEQ ID NO:4 (see for example, paragraph 0121 at page 36). Applicant is required to cancel the new matter in response to this office action.
Should applicant disagree with the examiner’s factual determination above, applicant should provide evidence that either or both of the provisional applications provide support for the invention now claimed in the manner required by 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. This could be accomplished, for example, by pointing to the specific page and line numbers within the specification, which disclose each limitation of the claimed invention.
Maintained-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 1-5 and 7-8 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. This is a written description rejection.
The purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. 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. Dianwnd 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.
Independent claim 1 requires administering to a subject a generic vector encoding a generic SDF-1 polypeptide wherein the effective amount of said vector induces exosome production, secretion, and/or function in the subject as part of a method of treating an ischemic condition or a cardiomyopathy. Dependent claims recite that the inhibitor is at least 90% identical to SEQ ID NO: 4 (noting that an equivalent having 95% identity to SEQ ID NO: 4 that is constitutively active is also recited (see for example, claim 5)).
Likewise, claim 3, depending from claim 1, requires administering a generic vector encoding a generic CAMKK1 polypeptide to a subject as part of a method of treating an ischemic condition or a cardiomyopathy. Dependent claims recite that the inhibitor is at least 90% identical to SEQ ID NO: 1 (see for example, claim 7).
Claims 2, 4, and 8, through dependency, incorporate and fail to further describe the above noted vector encoding an SDF-1 polypeptide and/or vector encoding a CAMKK1 polypeptide.
The specification teaches that a “CAMKK1 polypeptide” can comprise, or alternatively consist essentially of, or yet further consist of SEQ ID NO: 1 or 2, or an equivalent of each thereof (see for example paragraph 0006 of the specification). The specification further teaches that an “SDF-1 polypeptide” can comprise, or alternatively consist essentially of, or yet further consist of SEQ ID NO: 3 or 4, or an equivalent of each thereof (see for example paragraph 0006 of the specification). The specification additionally teaches that a nonlimiting example of the polynucleotide/vector encoding the CAMKK1 or SDF-1 polypeptide can comprise, or alternatively consist essentially of, or yet further consist of the polypeptide encoding SEQ ID NO: 1 or 2 (or their equivalents) or SEQ ID NO: 3 or 4 (or their equivalents), respectively (see the specification at paragraph 0011). The specification only teaches two examples of SDF-1 polypeptides encoded by the claimed vector(s) and two examples of CAMKK1 polypeptides encoded by the claimed vector(s). No conserved structure is indicated as required to function in the method as claimed, because the 10% variation can occur anywhere within the claimed SEQ ID NOs. Therefore, in view of this disclosure, Applicant is claiming a broad genus of SDF-1 and CAMKK1 polypeptide-encoding vectors without a representative number of species of said genera or a clearly demonstrated structure/function correlation. The specification does not provide adequate written description for the entire claimed genera of species encompassed by the claims including those having only at least 90% identity to the recited SEQ ID NOs, because in the absence of empirical determination, one skilled in the art would be unable to immediately envision, recognize, or distinguish at least most of the members comprised within the genera claimed, specifically, which mutants/variants encompassed by the genus would function as claimed in the method(s).
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. Applicant has not disclosed species other than those having 100% sequence identity to the enumerated SEQ ID NOs for consideration (and only mentions an identity of 90% generically at paragraph 0046 of the specification). Thus, given the substantial structure variation within the genera as well as the high level of unpredictability in the art, the disclosure of four species is not sufficiently representative of the entire genus.
Although screening techniques can be used to isolate variant polypeptides (and the vectors/nucleotides encoding them) that possess the ability to function as claimed, Applicant is reminded that the written description requirement of 35 U.S.C. 112 is severable from the enablement provision. As stated in Vas-Cath Inc. v. Mahurkar (CA FC) 19 USPQ2d 1111, 935 F2d 1555, “The purpose of the 'written description' requirement is broader than to merely explain how to 'make and use'; the applicant must also 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.”
Applicant is further directed to In re Alonso (545 F.3d 1015 (Fed. Cir. 2008), which involved claims that were directed to methods of using antibodies wherein the court found that the claims lacked adequate written description for the recited genus of antibodies recited in the methods. (C) See p. 8, 3rd paragraph, where Applicant argues that the claims recite all essential features of the invention. Therefore, products used in methods are rightfully subject to the written description requirement.
Regarding the state of the art, Listov et al (Opportunities and challenges in design and optimization of protein function. Nat Rev Mol Cell Biol 25, 639–653 (2024)) teach that the primary amino acid sequence determines downstream structure (protein folding), which then determines function (presenting both the inverse folding problem and the inverse function problem (see for example, Figure 1 and its caption; see also Mishra et al (Inaccurate secondary structure predictions often indicate protein fold switching. Protein Sci. 2019 Aug;28(8):1487-1493. doi: 10.1002/pro.3664. Epub 2019 Jun 17)). Expanding on these problems in proteomics, Reardon (Nature 635, 246-248 (2024)) explains that the goal of designing a protein with known and predictable function, binding partners, size, location, and other traits is, for the moment, a dream. Reardon teaches that further challenges in protein design include predicting how a protein, even if it binds to target, will function upon said binding. Reardon teaches that the primary structure (amino acid sequence) of a protein is critical to function, noting that even proteins of similar shape do not execute the same functions, while those with different shapes may carry out the same tasks. Reardon goes on to teach that it is not always apparent which parts of the primary sequence are important; a seemingly useless amino-acid chain on the side of an enzyme, for instance, might affect how tightly a protein can bind to other molecules or its ability to flip between conformational states. Moreover, Reardon explains that when researchers attempt to solve the structure of a protein experimentally, they often end up seeing only the most stable conformation, which is not necessarily the form the protein takes when it is active (see for example, pages 246-247 of Reardon).
Therefore, the genera of claimed vectors comprising a polynucleotide encoding an SDF-1 polypeptide or a CAMKK1 polypeptide, including the polynucleotides/vectors encoding an equivalent peptide or a peptide having 90% identity to the recited SEQ ID NOs, are insufficiently described through a demonstrated correlation of a conserved/identifying structure with the claimed function(s) or through a representative number of species. Only species having 100% identity to the recited SDF-1 and/or CAMKK1 sequences are considered sufficiently described. Therefore, claims 1-5 and 7-8 are deemed to fail to meet the written description requirement, as presently drafted.
New 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 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2, 5, and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Penn2015 (WO2015168145A1; as previously cited in the office action dated 02/19/2025) in view of Saxena et al (Stromal cell-derived factor-1alpha is cardioprotective after myocardial infarction. Circulation. 2008 Apr 29;117(17):2224-31. doi: 10.1161/CIRCULATIONAHA.107.694992. Epub 2008 Apr 21.; as previously cited in the office action dated 02/19/2025).
Regarding claims 1 and 5, Penn2015 teaches a method of treating a subject having advanced ischemic cardiomyopathy (known in the art to result in ischemic tissue injury), the method comprising administering to said subject a therapeutically effective amount of a plasmid encoding SDF-1 (see for example, claim 1 of Penn2015), wherein the subject suffers from advanced ischemic cardiomyopathy (see Penn2015 claim 2). The method comprises administering to said subject a therapeutically effective amount of a plasmid encoding SDF-1 if the subject's end systolic volume is indicative of advanced ischemic cardiomyopathy (see for example, Penn2015 at claim 6), wherein the SDF-1 encoding plasmid is administered directly to, or expressed locally in, a weakened, ischemic, and/or peri-infarct region of myocardial tissue of the subject (see for example, Penn2015 at the abstract). Penn2015 teaches the use of an SDF-1 polypeptide that is sequentially identical to instant SEQ ID NO: 4 (see for example, Penn2015’s SEQ ID NO: 2 and paragraphs 0103 and 0110). Penn2015 teaches that CXCR4 is the primary receptor for SDF-1 (see for example, paragraphs 0053, 0182, 0187, 0282 (suggesting CXCR4 is already present, upregulated, an expressed in injured tissue such as inflamed or ischemic tissue), and Figure 16 of Penn2015)).
Penn2015 does not explicitly teach that the amount of SDF-1 vector administered induces exosome production/secretion/function.
However, Saxena et al teach that SDF-1α can attract CXCR4-expressing hematopoietic stem cells to the heart, where they are assumed to take up residence and improve cardiac function. The mechanism by which the stem cells might improve function remains unclear. Whether stem cells differentiate into functional cardiomyocytes has been in dispute, but recent studies have suggested that secreted signals arising from stem cells may somehow potentiate cardiac regeneration or repair (see for example, page 6/16) at the SDF-1α Promotes Survival of Ischemic Myocardium section).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of Penn2015 and Saxena et al. The artisan would have been motivated to make and use the invention as claimed because Penn2015 teaches that the method is successful for treating injury related to ischemia/cardiomyopathy (see for example, the abstract). Penn2015 further teaches and make obvious local administration of the vector encoding SDF-1 in the presence of its known receptor CXCR4 (see for example, paragraphs 0053, 0182, 0187, 0282 (suggesting CXCR4 is already present and upregulated in injured tissue such as inflamed or ischemic tissue and noting SDF-1 therapy capitalizes on increased, indefinitely prolonged, localized expression of CXCR4 in injured tissue), and Figure 16 of Penn2015), which would have made obvious administration/expression of SDF-1 in the presence of its known receptor (CXCR4), which would have been understood by the artisan to mean administration local to the site of tissue injury/ischemia. Practicing the method of directly/locally administering the polynucleotide encoding SDF-1 would have been obvious for reasons iterated above. Administration of an amount effective to treat the ischemic condition (the amount used in Penn2015) would have, absent evidence to the contrary, been an ‘effective amount’ as recited (defined throughout the instant disclosure only as an amount sufficient to induce exosome production/secretion/function; noting that no amount/dose of the vector is clearly provided in the instant disclosure), absent evidence to the contrary, such that it appears Applicant’s claims are to the mechanism by which the prior art method effects treatment. The MPEP provides that:
"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel." Id. See also MPEP 2112(I) with regard to inherency and product-by-process claims and MPEP § 2141.02 with regard to inherency and rejections under 35 U.S.C. 103,”
(see MPEP 2112(I)). Therefore, the cited references and teachings cited herein (above) are held to make obvious, as of the filing date, local administration of a vector encoding SDF-1 in the presence of CXCR4 for treating an ischemic condition such as cardiomyopathy.
Regarding claim 2, as discussed above, the method of Penn2015 as understood in light of Saxena et al is successful in effecting therapeutic change in ischemic, cardiac (injured) tissue (see for example, the abstract, claim 1, and paragraphs 0252-0253 of Penn2015). Where Penn2015 does not explicitly mention that the amount of polynucleotide locally administered to the injured tissue is an amount that induces exosome production, secretion, and/or function, it is noted that the amount administered in Penn2015 is effective for the shared goal of treating an ischemic condition or a cardiomyopathy, as instantly claimed. As noted above, the discovery of a mechanism by which a known product or process functions is not sufficient to overcome obviousness. The MPEP provides that, with respect to rejections under 35 USC §102 or §103, “[t]he inherent teaching of a prior art reference, a question of fact, arises both in the context of anticipation and obviousness.” In re Napier, 55 F.3d 610, 613, 34 USPQ2d 1782, 1784 (Fed. Cir. 1995),” (see MPEP §2112). Applicant's attention is further directed to MPEP § 2112 (II), which states, "there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003)." The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Therefore, the steps of locally administering a vector encoding an SDF-1 polypeptide to a subject for treating an ischemic condition or a cardiomyopathy are taught and made obvious by the combination of Penn2015 and Saxena et al, where the artisan would have had a reasonable expectation of success in light of the prior art disclosures.
Regarding claim 8, as discussed above, the SDF-1 encoding plasmid is administered directly to, or expressed locally in, a weakened, ischemic, and/or peri-infarct region of myocardial tissue of the subject (see for example, Penn2015 at the abstract). This is deemed to read upon and make obvious, with a reasonable expectation of success before the effective filing date, local administration into a peri-infarct zone of injured tissue.
Claims 3-4 and 7 are rejected under 35 U.S.C. 103 as being unpatentable over Penn2015 in view of Saxena et al, as applied to claims 1-2, 5, and 8 above, in further view of Penn (WO2016089826A1; as cited in the 11/22/2023 IDS).
Regarding claims 3-4, as noted above, Penn2015 and Saxena et al teach the method of instant claim 1.
Penn2015 and Saxena et al do not teach administration of a vector encoding CAMKK1.
However, Penn teaches a method of treating an ischemic or inflammatory condition
(understood to include treating resultant tissue injury) (wherein the ischemic or inflammatory condition is acute myocardial infarction, heart failure, peripheral artery disease, stroke, liver disease, ischemic kidney disease, multiple sclerosis, traumatic brain injury, spinal cord injury, graft versus host disease (GVHD), diabetes, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, an injury from a solid organ transplant, an orthopedic injury, a cartilage disorder, a wound, or any combination thereof) in an organ or tissue of a patient, comprising inducing an increase of the level of CAMKK1 in said organ or tissue (see for example, Penn at claims 1 and 19) wherein said organ or tissue may be the heart (myocardium) (see for example, Penn at claims 2-3) wherein the increase in the level of CAMKK1 in said organ or tissue is achieved by administering a vector comprising a nucleic acid encoding CAMKK1, where said vector may be administered systemically (distal to the site of action/tissue that is injured; see the claim interpretation section above) (see for example, paragraph 0043, embodiment 17, and claim 17 of Penn). Note that the vector may be a plasmid or a viral vector (see for example, Penn at claim 6).
Penn further teaches that there is no effect of CAMKKl on SDF-1 and there is no effect of SDF-1 on CAMKKl expression. The CAMKKl administration/approach appears to have the potential to be completely synergistic and not redundant to SDF-1 (see for example, paragraph 0061). CAMKKl was identified as a key regulator of myocardial stem cell (MSC) function. The fact that the SDF-1:CXCR4 axis and CAMKKl have no molecular overlap with respect to induced expression suggests that a combination of CAMKKl and SDF-1 should have synergistic effects, most obviously in acute injury, and likely in chronic tissue injury. The disclosed methods induce the enhancement of the regenerative secretome (secreted molecules) from multiple cell types, including MSCs. Without intending to be bound by theory, Penn teaches that the increased levels of CAMKK1 result in enhanced functional benefit through alteration of secreted factors from those cells expressing CAMKK1. This secretome induction can be used as a novel regenerative therapeutic (see for example, paragraphs 0062-0063 of Penn; also see paragraph 0055 of Penn which discusses data demonstrating that modulation of CAMKK1 does alter the MSC secretome and subsequent myocardial repair through potentially multiple mechanisms).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of Penn2015, Saxena et al, and Penn. The artisan would have been motivated to make and use the invention as claimed because Penn2015 and Penn teaches methods for treating an ischemic condition in the myocardium and Penn teaches that the SDF-1 and CAMKK1 interact synergistically to accomplish that shared goal, as disused above. Absent evidence to the contrary, it is presumed that the amount of SDF-1 encoding vector in Penn2015 and the amount of CAMKK1 encoding vector administered in Penn is an effective amount, as instantly recited, to induce exosome production, secretion, and/or function because the prior art methods teach treatment of tissue injured by ischemia. Further, where the instant disclosure does not provide what the effective amount may be through providing a clear dose/range of dosages of the claimed vector(s), it is presumed that the prior art amounts of SDF-1 encoding and CAMKK1 encoding vectors, taught to be effective for treating the same condition(s) as instantly claimed to be treated, would be an effective amount so as to meet the limitation of administering an effective amount of said vectors. The MPEP provides that:
"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel." Id. See also MPEP 2112(I) with regard to inherency and product-by-process claims and MPEP § 2141.02 with regard to inherency and rejections under 35 U.S.C. 103,”
(see MPEP 2112(I)). The MPEP further provides that, with respect to rejections under 35 USC §§120 and 103, “[t]he inherent teaching of a prior art reference, a question of fact, arises both in the context of anticipation and obviousness.” In re Napier, 55 F.3d 610, 613, 34 USPQ2d 1782, 1784 (Fed. Cir. 1995),” (see MPEP §2112). Applicant's attention is further directed to MPEP § 2112 (II), which states, "there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003)." The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Regarding claim 7, Penn teaches a CAMKK1 polypeptide that is sequentially identical to instant SEQ ID NO: 1 (see for example, Penn’s SEQ ID NO: 2 and paragraph 0030; encoded by a nucleotide of Penn’s SEQ ID NO: 1 see, for example paragraph 0027). One of ordinary skill in the art would have found it desirable to use a vector encoding this CAMKK1 because Penn teaches that it is successful in treating inflammatory or ischemic conditions (see for example, the abstract and claims 1 and 5).
New Rejections - 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 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 1-5 and 8 are rejected on the ground of nonstatutory double patenting as being unpatentable over of claims 1-11 of reference A (US11273208B2) in view of Penn2015 (WO2015168145A1) and Saxena et al (Stromal cell-derived factor-1alpha is cardioprotective after myocardial infarction. Circulation. 2008 Apr 29;117(17):2224-31. doi: 10.1161/CIRCULATIONAHA.107.694992. Epub 2008 Apr 21.).
Regarding claims 1 and 3-5, reference A claims a method of increasing vascular density comprising systemically administering cells comprising a vector encoding CAMKK1 (see for example, claims 1 and 4 of reference A).
Reference A does not claim administration of a vector encoding SDF-1.
However, Penn2015 teaches a method of treating a subject having advanced ischemic cardiomyopathy (known to result in ischemic tissue injury), the method comprising administering to said subject a therapeutically effective amount of a plasmid encoding SDF-1 (see for example, claim 1 of Penn2015), wherein the subject suffers from advanced ischemic cardiomyopathy (see for example, Penn2015 at claim 2). The method comprises administering to said subject a therapeutically effective amount of a plasmid encoding SDF-1 if the subject's end systolic volume is indicative of advanced ischemic cardiomyopathy (see for example Penn2015 at claim 6), wherein the SDF-1 encoding plasmid is administered directly to, or expressed locally in, a weakened, ischemic, and/or peri-infarct region of myocardial tissue of the subject (see for example, Penn2015 at the abstract). Penn2015 further teaches that CXCR4 is the primary receptor for SDF-1 (see for example, paragraphs 0053, 0182, 0187, 0282 (suggesting CXCR4 is already present and upregulated in injured tissue such as inflamed or ischemic tissue), and Figure 16 of Penn2015). Penn2015 teaches the use of an SDF-1 polypeptide that is sequentially identical to instant SEQ ID NO: 4 (see for example, Penn2015’s SEQ ID NO: 2 and paragraphs 0103 and 0110). One of ordinary skill in the art would have found it obvious to use this polypeptide in the method of Penn2015 because Penn2015 teaches that this is successful (see for example, paragraphs 0252-0253).
Penn2015 does not explicitly teach that the amount of SDF-1 vector administered induces exosome production/secretion/function.
However, Saxena et al teach that SDF-1α can attract CXCR4-expressing hematopoietic stem cells to the heart, where they are assumed to take up residence and improve cardiac function. The mechanism by which the stem cells might improve function remains unclear. Whether stem cells differentiate into functional cardiomyocytes has been in dispute, but recent studies have suggested that secreted signals arising from stem cells may somehow potentiate cardiac regeneration or repair (see for example, page 6/16).
It would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of reference A in view of Penn2015 and Saxena et al. The artisan would have been motivated to make and use the invention as claimed because Penn2015 teaches that the method is successful for treating injury related to ischemia/cardiomyopathy (see for example, the abstract). Practicing the method of directly/locally administering the polynucleotide encoding SDF-1 would have been obvious and an amount effective to treat the ischemic condition (the amount used in Penn2015) would have, absent evidence to the contrary, been an amount effective to induce exosome production/secretion/function, absent evidence to the contrary such that it appears Applicant’s claims are drawn to the mechanism by which the prior art method effects treatment. The MPEP provides that:
"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel." Id. See also MPEP 2112(I) with regard to inherency and product-by-process claims and MPEP § 2141.02 with regard to inherency and rejections under 35 U.S.C. 103,”
(see MPEP 2112(I)). Therefore, the cited references and teachings cited herein (above) are held to make obvious, as of the filing date, local administration of a vector encoding SDF-1 in the presence of CXCR4 for treating an ischemic condition such as cardiomyopathy.
Regarding claim 2, as discussed above, the method of Penn2015 as understood in light of Saxena et al is successful in effecting therapeutic change in ischemic, cardiac (injured) tissue (see for example, the abstract, claim 1, and paragraphs 0252-0253 of Penn2015). Where Penn2015 does not explicitly mention that the amount of polynucleotide locally administer to the injured tissue is an amount that induces exosome production, secretion, and/or function, it is noted that the amount administered in Penn2015 is effective for the shared goal of treating an ischemic condition or a cardiomyopathy, as instantly claimed. As noted above, the discovery of a mechanism by which a known product or process functions is not sufficient to overcome obviousness. The MPEP provides that, with respect to rejections under 35 USC §§ 102 and 103, “[t]he inherent teaching of a prior art reference, a question of fact, arises both in the context of anticipation and obviousness.” In re Napier, 55 F.3d 610, 613, 34 USPQ2d 1782, 1784 (Fed. Cir. 1995),” (see MPEP §2112). Applicant's attention is further directed to MPEP § 2112 (II), which states, "there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003)." The artisan would have had a reasonable expectation of success based on the cumulative disclosures of these prior art references.
Regarding claim 8, as discussed above, Penn2015 teaches a method wherein the SDF-1 encoding plasmid is administered directly to, or expressed locally in, a weakened, ischemic, and/or peri-infarct region of myocardial tissue of the subject (see for example, Penn2015 at the abstract.
Claim 7 is rejected on the ground of nonstatutory double patenting as being unpatentable over of claims 1-11 of reference A (US11273208B2), Penn2015, and Saxena et al, as applied to claims 1-5 and 8 above, in further view of Penn (WO2016089826A1).
Regarding claim 7, the combination of reference A, Penn2015, and Saxena et al do not teach a CAMKK1 having the instantly claimed SEQ ID NO: 1 or 2 or 90% identity thereto.
However, Penn teaches a CAMKK1 polypeptide that is sequentially identical to instant SEQ ID NO: 1 (see for example, Penn’s SEQ ID NO: 2 and paragraph 0030; encoded by a nucleotide of Penn’s SEQ ID NO: 1 see for example, paragraph 0027). One of ordinary skill in the art would have found it desirable to use a vector encoding this CAMKK1 because Penn teaches that it is successful in treating inflammatory or ischemic conditions where vascular density is a measure of therapeutic effect (see for example, the abstract, claims 1 and 5, and paragraph 0012).
Claims 1-2, 5, and 8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 8 of reference B (US 9844581B2) in view of Penn2015 (WO2015168145A1) and Saxena et al (Stromal cell-derived factor-1alpha is cardioprotective after myocardial infarction. Circulation. 2008 Apr 29;117(17):2224-31. doi: 10.1161/CIRCULATIONAHA.107.694992. Epub 2008 Apr 21.).
Regarding claims 1-2, 5, and 8, reference B claims a method of treating an ischemic cardiomyopathy in mammal comprising administering to weakened, ischemic, or peri-infarct tissue a vector encoding SDF-1 (see for example, claim 8).
Reference B does not explicitly claim that local administration is in an amount sufficient to induce exosome secretion, production, and/or function.
However, Penn2015 teaches a method of treating a subject having advanced ischemic cardiomyopathy, the method comprising administering to said subject a therapeutically effective amount of a plasmid encoding SDF-1 (see for example, claim 1 of Penn2015), wherein the subject suffers from advanced ischemic cardiomyopathy (see for example, Penn2015 at claim 2). The method comprises administering to said subject a therapeutically effective amount of a plasmid encoding SDF-1 if the subject's end systolic volume is indicative of advanced ischemic cardiomyopathy (see for example, Penn2015 at claim 6), wherein the SDF-1 encoding plasmid is administered directly to, or expressed locally in, a weakened, ischemic, and/or peri-infarct region of myocardial tissue of the subject (see for example, Penn2015 at the abstract). Penn2015 teaches that CXCR4 is the primary receptor for SDF-1 (see for example, paragraphs 0053, 0182, 0187, 0282 (suggesting CXCR4 is already present and upregulated in injured tissue such as inflamed or ischemic tissue), and Figure 16 of Penn2015). Penn2015 teaches the use of an SDF-1 polypeptide that is sequentially identical to instant SEQ ID NO: 4 (see for example, Penn2015’s SEQ ID NO: 2 and paragraphs 0103 and 0110).
Therefore, the artisan would have found it prima facie obvious to locally administer a vector encoding SDF-1 to a subject with ischemic injury, such as from cardiomyopathy, because the known receptor of SDF-1 is CXCR4, which is locally expressed in injured tissue. The artisan would have had a reasonable expectation of success in treating an ischemic or cardiomyopathy condition therefore, in light of the disclosures of the cited prior art.
One of ordinary skill in the art would have found it obvious to use this polypeptide in the method of Penn2015 because Penn2015 teaches that this is successful (see for example, the abstract). It would have been prima facie obvious to practice the method of administering a vector encoding SDF-1 to treat an ischemic condition, as taught by the references cited herein, such that the artisan would have had a reasonable expectation of success.
Claims 3-4 and 7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 8 of reference B (US 9844581B2) in view of Penn2015 and Saxena et al, as applied to claims 1-2, 5, and 8 above, in further view of Penn (WO2016089826A1).
Regarding claim 3, as discussed above, reference B, Penn2015, and Saxena et al teach the method of claim 1.
The cited references do not teach administration of a vector encoding CAMKK1.
However, Penn teaches a method of treating an ischemic or inflammatory condition (wherein the ischemic or inflammatory condition is acute myocardial infarction, heart failure, peripheral artery disease, stroke, liver disease, ischemic kidney disease, multiple sclerosis, traumatic brain injury, spinal cord injury, graft versus host disease (GVHD), diabetes, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, an injury from a solid organ transplant, an orthopedic injury, a cartilage disorder, a wound, or any combination thereof) in an organ or tissue of a patient, comprising inducing an increase of the level of CAMKK1 in said organ or tissue (see for example, Penn at claims 1 and 19) wherein said organ or tissue may be the heart (myocardium), liver, kidney, brain, spine, lungs, small intestine, large intestine, arteries, joints, cartilage, skin, or any combination thereof (see for example, claims 2-3 of Penn), wherein the increase in the level of CAMKK1 in said organ or tissue is achieved by administering a vector comprising a nucleic acid encoding CAMKK1 to said organ or tissue (see for example, Penn at claim 5). Note that the vector may be a plasmid or a viral vector (see for example, Penn at claim 6).
Penn further teaches that there is no effect of CAMKKl on SDF-1 and that there is no effect of SDF-1 on CAMKKl expression (data not shown). The CAMKKl administration/approach appears to have the potential to be completely synergistic and not redundant to SDF-1 (see for example, paragraph 0061). CAMKKl was identified as a key regulator of MSC function. The fact that the SDF-1:CXCR4 axis and CAMKKl have no molecular overlap with respect to induced expression suggests that a combination of CAMKKl and SDF-1 should have synergistic effects, most obviously in acute injury, and likely in chronic tissue injury. The disclosed methods induce the enhancement of the regenerative secretome (secreted molecules) from multiple cell types, including MSCs. Without intending to be bound by theory, it is believed that the increased levels of CAMKK1 result in enhanced functional benefit through alteration of secreted factors from those cells expressing CAMKK1. This secretome induction can be used as a novel regenerative therapeutic (see for example, paragraphs 0062-0063 of Penn; also see also paragraph 0055 discussing data demonstrating that modulation of CAMKK1 alters the MSC secretome and subsequent myocardial repair through potentially multiple mechanisms). In light of these teachings, it is presumed that the amount of the CAMKK1-encoding vector administered in the method of Penn causes an increase in CAMKK1 sufficient to influence the secretome (a system of secreted factors including exosomes; induce/secrete exosomes) so as to treat an ischemic/inflammatory condition in a subject such that Penn teaches administration of an effective amount, as instantly recited, of a vector encoding CAMKK1 as instantly claimed, absent evidence to the contrary.
Regarding claim 4, Penn teaches that the vector encoding CAMKK1 may be administered systemically, to the site, or to a peripheral site (see for example, paragraph 0043 of Penn), which is held to make obvious the limitation of distal administration as Penn teaches systemic administration (distal administration) is a successful method of administering said CAMKK1 encoding vector.
Regarding claim 7, Penn teaches a CAMKK1 polypeptide that is sequentially identical to instant SEQ ID NO: 1 (see for example, Penn’s SEQ ID NO: 2 and paragraphs 0027 and 0030, where SEQ ID NO: 1 of Penn is the nucleic acid sequence encoding the CAMKK1 polypeptide).
One of ordinary skill in the art would have found it obvious as of the filing date to use this polypeptide because Penn teaches that it is successful in treating inflammatory or ischemic conditions (see for example, the abstract and claims 1 and 5 of Penn). The artisan would have been motivated with a reasonable expectation of success to combine the references cited herein to take advantage of the therapeutic synergy taught by Penn (see for example, paragraph 0061).
Claims 1-2, 5, and 8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of reference C (US Application No. 17/667,375) in view of Penn2015 (WO2015168145A1), and Saxena et al (Stromal cell-derived factor-1alpha is cardioprotective after myocardial infarction. Circulation. 2008 Apr 29;117(17):2224-31. doi: 10.1161/CIRCULATIONAHA.107.694992. Epub 2008 Apr 21.).
Note that this is a provisional rejection.
Regarding claims 1-2, 5, and 8, reference C teaches a method of treating an ischemic or inflammatory condition (which may be cardiomyopathy, acute myocardial infarction, heart failure, etc.) in an organ or tissue (which may be the heart) of a patient comprising administering cells comprising a vector (nucleic acid) encoding CAMKK1.
Reference C does not teach administration of a vector encoding SDF-1.
However, Penn2015 teaches a method of treating a subject having advanced ischemic cardiomyopathy, the method comprising administering to said subject a therapeutically effective amount of a plasmid encoding SDF-1 (see for example, claim 1 of Penn2015), wherein advanced ischemic cardiomyopathy (see for example, Penn2015 at claim 2). The method comprises administering to said subject a therapeutically effective amount of a plasmid encoding SDF-1 if the subject's end systolic volume is indicative of advanced ischemic cardiomyopathy (see for example, Penn2015 at claim 6), wherein the SDF-1 encoding plasmid is administered directly to, or expressed locally in, a weakened, ischemic, and/or peri-infarct region of myocardial tissue of the subject (see for example, Penn2015 at the abstract). Penn2015 further teaches that CXCR4 is the primary receptor for SDF-1 (see for example, paragraphs 0053, 0182, 0187, 0282 (suggesting CXCR4 is already present and upregulated in injured tissue such as inflamed or ischemic tissue), and Figure 16 of Penn2015). Penn2015 teaches the use of an SDF-1 polypeptide that is sequentially identical to instant SEQ ID NO: 4 (see for example, Penn2015’s SEQ ID NO: 2 and paragraphs 0103 and 0110). One of ordinary skill in the art would have found it obvious to use this polypeptide in the method of Penn2015 because Penn2015 teaches that this is successful (see for example, the abstract of Penn2015).
Reference C and Penn2015 do not explicitly teach that the amount of SDF-1 vector administered induces exosome production/secretion/function.
However, Saxena et al teach that SDF-1α can attract CXCR4-expressing hematopoietic stem cells to the heart, where they are assumed to take up residence and improve cardiac function. The mechanism by which the stem cells might improve function remains unclear. Whether stem cells differentiate into functional cardiomyocytes has been in dispute, but recent studies have suggested that secreted signals arising from stem cells may somehow potentiate cardiac regeneration or repair (see for example, page 6/16).
Therefore, the method of administering the compounds as claimed would have been obvious and an amount effective to treat the ischemic condition would have, presumably, been an amount effective to induce exosome production/secretion/function, absent evidence to the contrary such that it appears Applicant’s claims are to the mechanism by which the prior art method effects treatment. The MPEP provides that:
"[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel." Id. See also MPEP 2112(I) with regard to inherency and product-by-process claims and MPEP § 2141.02 with regard to inherency and rejections under 35 U.S.C. 103,”
(see MPEP 2112(I)). Therefore, the combination of cited references (as cited herein) are held to make obvious as of the filing date administration of a vector encoding CAMKK1 and/or SDF-1 in the presence of CXCR4 for treating an ischemic condition such as cardiomyopathy.
The MPEP additionally provides that:
“It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In reKerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted) (Claims to a process of preparing a spray-dried detergent by mixing together two conventional spray-dried detergents were held to be prima facie obvious.). See also In reCrockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960) (Claims directed to a method and material for treating cast iron using a mixture comprising calcium carbide and magnesium oxide were held unpatentable over prior art disclosures that the aforementioned components individually promote the formation of a nodular structure in cast iron.); and Ex parteQuadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992) (mixture of two known herbicides held prima facie obvious),”
(see MPEP section 2144.06(I)). Therefore, one of ordinary skill in the art would have found it obvious as of the filing date to locally administer a vector encoding SDF-1 (having the amino acid sequence of instant SEQ ID NO: 4) in the presence of CXCR4 alone to treat an ischemic condition, or in tandem with administering a vector encoding a CAMKK1 having an amino acid sequence identical to instant SEQ ID NO: 1 in light of the above cited sequences given that administration of both vectors (SDF-1-encoding and CAMKK1-encoding are both individually taught to be useful for treating an ischemic condition such as cardiomyopathy).
Claims 3-4 and 7 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of reference C (US Application No. 17/667,375) in view of Penn2015 and Saxena et al, as applied to claims 1-2, 5, and 8 above, in further view of Penn (WO2016089826A1).
Note that this is a provisional rejection.
Regarding claim 3, as discussed above, reference C, Penn2015, and Saxena et al teach the method of claim 1.
The cited references do not teach distal administration of a vector encoding CAMKK1.
However, Penn teaches a method of treating an ischemic or inflammatory condition (wherein the ischemic or inflammatory condition is acute myocardial infarction, heart failure, peripheral artery disease, stroke, liver disease, ischemic kidney disease, multiple sclerosis, traumatic brain injury, spinal cord injury, graft versus host disease (GVHD), diabetes, chronic obstructive pulmonary disease (COPD), rheumatoid arthritis, an injury from a solid organ transplant, an orthopedic injury, a cartilage disorder, a wound, or any combination thereof) in an organ or tissue of a patient, comprising inducing an increase of the level of CAMKK1 in said organ or tissue (see for example, Penn at claims 1 and 19) wherein said organ or tissue may be the heart (myocardium), liver, kidney, brain, spine, lungs, small intestine, large intestine, arteries, joints, cartilage, skin, or any combination thereof (see for example, claims 2-3), wherein the increase in the level of CAMKK1 in said organ or tissue is achieved by administering a vector comprising a nucleic acid encoding CAMKK1 to said organ or tissue (see for example, Penn at claim 5). Note that the vector may be a plasmid or a viral vector (see for example, Penn at claim 6).
Penn further teaches that there is no effect of CAMKKl on SDF-1 and that there is no effect of SDF-1 on CAMKKl expression (data not shown). The CAMKKl administration/approach appears to have the potential to be completely synergistic and not redundant to SDF-1 (see for example, paragraph 0061). CAMKKl was identified as a key regulator of MSC function. The fact that the SDF-1:CXCR4 axis and CAMKKl have no molecular overlap with respect to induced expression suggests that a combination of CAMKKl and SDF-1 should have synergistic effects, most obviously in acute injury, and likely in chronic tissue injury. The disclosed methods induce the enhancement of the regenerative secretome (secreted molecules) from multiple cell types, including MSCs. Without intending to be bound by theory, it is believed that the increased levels of CAMKK1 result in enhanced functional benefit through alteration of secreted factors from those cells expressing CAMKK1. This secretome induction can be used as a novel regenerative therapeutic (see for example, paragraphs 0062-0063 of Penn; also see also paragraph 0055 discussing data demonstrating that modulation of CAMKK1 alters the MSC secretome and subsequent myocardial repair through potentially multiple mechanisms). In light of these teachings, it is presumed that the amount of CAMKK1 vector administered in the method of Penn causes an increase in CAMKK1 sufficient to influence the secretome (a system of secreted factors including exosomes; induce/secrete exosomes) so as to treat an ischemic/inflammatory condition in a subject such that Penn teaches administration of an effective amount of vector encoding CAMKK1 as instantly claimed, absent evidence to the contrary.
Regarding claim 4, Penn teaches that the vector may be administered systemically, to the site, or to a peripheral site (see for example, paragraph 0043 of Penn), which is held to make obvious the limitation of distal administration because Penn teaches that systemic administration (distal administration) is a successful method of administering said CAMKK1-encoding vector (see for example, the abstract).
Regarding claim 7, Penn teaches a CAMKK1 polypeptide that is sequentially identical to instant SEQ ID NO: 1 (see for example, Penn’s SEQ ID NO: 2 and paragraphs 0027 and 0030, noting that Penn’s SEQ ID NO: 1 is the nucleotide encoding the peptide of Penn’s SEQ ID NO: 2).
One of ordinary skill in the art would have found it obvious as of the filing date to use a vector encoding this polypeptide because Penn teaches this approach is successful in treating inflammatory or ischemic conditions (see for example, the abstract and claims 1 and 5 of Penn). The artisan would have been motivated with a reasonable expectation of success to combine the references cited herein to take advantage of the therapeutic synergy taught by Penn (see for example, paragraph 0061).
Applicant’s Arguments and Responses
A. Applicant argues that the combined cited prior art references (Penn, Penn2015, and Saxena et al) do not teach an effective amount of vector as claimed because the references do not explicitly teach that the amount administered induces production, secretion, and/or function of exosomes and do not teach local delivery/administration of the SDF-1 vector.
Response: This is unpersuasive. There is no evidence that the prior art methods do not result in production, secretion, and/or function of exosomes. Further, the discovery of a mechanism by which the methods of the prior art effect treatment of ischemic conditions (such as treating tissue injured by ischemia due to cardiomyopathy) do not make an otherwise obvious method newly patentable, as discussed above in greater detail. The prior art compositions administered, route of administration, and the population to be treated are the same (such that the resulting effects are presumed to be the same given that function flows from structure). The only difference could be one of dosage which is not claimed or disclosed in the present Application. As noted above, Penn2015 does teach local administration where Penn2015 teaches that “administered directly to, or expressed locally in, a weakened, ischemic, and/or peri-infarct region of myocardial tissue”, it is unclear what other reasonable interpretation the artisan would or could have made other than to understand that Penn2015 teaches local administration indistinct from the local administration presently claimed. Penn2015 additionally teaches CXCR4 is indefinitely, locally expressed in injured tissue, allowing administered SDF-1 therapy to capitalize on this feature of injured tissue (see for example, paragraph 0282 of Penn2015). The semantics are not merely similar, the local administration/expression to injured tissue expressing CXCR4 is explicitly mentioned. A mere allegation to the contrary which is not evidenced is insufficient to overcome what is clearly taught in the prior art. It appears Applicant’s invention is to the discovery of properties underlying the claimed method (exosome function/production/secretion). However, this is an inherent feature of practicing the prior art method and cannot be held to make patentable an otherwise known method absent an evidenced showing of some unpredictable result or criticality, neither of which have been demonstrated. Applicant denies this inherency, but has failed to articulate why administering structurally identical compounds via the same route, to the same population, for the same purpose, would not reasonable have the same downstream effects/results. There is no difference in the active steps required of reagents/vectors used which has been claimed or persuasively articulated. Applicant attacks the Saxena et al reference stating that it does not clearly teach that SDF-1 promotes exosome production/secretion/function. Saxena et al need not show this explicitly. The exosome production/secretion/function is clearly an inherent feature either of the claimed or the prior art method of administering structurally identical compounds via the same route, to the same population, for the same purpose. Applicant only points to this mechanistic discovery, but has not sufficiently shown a meaningful different between the reagents/active steps of the prior art method and the instantly claimed method. Therefore, the rejections of record are maintained at this time.
B. Applicant requests withdrawal of the rejections for double patenting alleging that references A, B, and C do not teach local administration of SDF-1.
Response: This has been fully considered but is not found to be persuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). References A, B, or C are never cited in isolation to reject any of the claims. The claims are made obvious by the combination of Penn 2015, Saxena et al, and Penn as cited in the rejections under 35 USC §103, where these references are then included in the rejections citing References A, B, or C. Any further argument of deficiency would appear to be redundant and sufficiently rebutted in the response to point A above. Therefore, the rejections for double patenting are maintained at this time.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ASHLEY GAO whose telephone number is (571) 272-5695. he examiner can normally be reached on M-F 9:00 am - 6:00 pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s
supervisor, Gregory Emch can be reached on (571) 272-8149. The fax phone number for the
organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent
Application Information Retrieval (PAIR) system. Status information for published applications
may be obtained from either Private PAIR or Public PAIR. Status information for unpublished
applications is available through Private PAIR only. For more information about the PAIR
system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR
system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would
like assistance from a USPTO Customer Service Representative or access to the automated
information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Ashley Gao/
Examiner, Art Unit 1678
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
Prosecution Insights