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 .
Status of Claims
This application was originally filed on 9/17/24 with claims 1-33. A preliminary amendment filed the same day amended claims 2, 6, 8, 9, 11, 13, 14, 16, 17, 19, 23, 25, 26, 28, and 30-32 and canceled claims 3-5, 7, 10, 12, 15, 20-22, 24, 27, 29, and 33. Claims 1-2 ,6, 8-9 ,11, 13, 16-19, 23, 25-26, 28, and 30-32 are pending and under examination on their merits.
Priority
This application claims benefit of provisional application 63/321,370, filed 3/18/22. As discussed below, the as-filed disclosure does not provide support for the claims as drafted because the written-description requirement is not met. As such, the effective filing date for prior-art purposes is 3/17/23, the date the parent PCT application was filed with WIPO.
Claim Objections
The claims are objected to for general illegibility. There is extensive pixelation throughout the claim listing, likely resulting from the use of dark gray or dark blue font. Applicant is invited to view the claim listing on Patent Center to see the listing in the Office’s records. Future claim listings should use only black font in order to ensure a clear record and to avoid delays at the printer.
Claims 2 and 19 contain periods other than within abbreviations and at the end of the claim and are therefore improper. See MPEP 608.01(m). Parentheses are encouraged to set off the (a), (b), and (c) designators.
Claims 2 and 19 misspell the word “Muparfostat,” for example at line 5 of claim 2. Correction is requested.
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 2, 9, 11, 12, 16, 17, 19, 26, and 32 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 2 is indefinite for reciting exemplary language throughout. The claim refers to “sulfated phosphomannopentaose (PI-88, Mupar[f]ostat).” This is confusing because “sulfated phosphomannopentaose” is generic to PI-88 (phosphomannopentaose bisulfate) and Muparfostat (phosphomannopentaose monosulfate). Examples and preferences are best set forth in the specification, not the claims. MPEP 2173.05(d). It is unclear whether the claim is limited to the species or whether the full genus is within its scope.
Next, claim 2 recites “such as” at lines 10 and 11 and “e.g.” at line 29. Similarly, claim 2 refers to “KI-105 series compounds,” which operates as “KI-105 type compounds,” which is indefinite. See MPEP 2173.05(d). It is unclear which compounds are “KI-105 series compounds.” Claim 2 also refers to “RK-682 series compounds,” which is indefinite for the same reason.
Claim 2 also defines the variables R1-R4 (lines 19-26) and then indicates that “optionally, R1, R2, and/or R3 are, independently, a C1-5 alkanoyl group.” (Line 28.) This “optionally” limitation does not serve to identify an alternative; rather, it functions to give examples or preferences for R1, R2, and/or R3. This is indefinite. See MPEP 2173.05(d).
Finally, claim 2 provides heparastatin HCl “having the exemplary structure” followed by a chemical-structure depiction. It is unclear whether heparastatin HCl is limited to that structure or not. Claim 2 should be amended such that it lists alternatives and is clear about what options are within its scope. Claim 19 suffers similar deficiencies throughout and should be amended similarly.
Claim 9 is indefinite for reciting exemplary language, specifically “optionally” at line 9. The word “optionally” here is not operating to identify an alternative to the tissue being in the form of the organ; it functions to give one example of a downstream treatment of the organ. See MPEP 2173.05(d). Examples and preferences lend confusion when they are included in a claim. Claim 23 suffers a similar deficiency and is also indefinite.
Claim 11 is indefinite for reciting exemplary language, specifically “e.g.” at line 3. See MPEP (d). Examples and preferences lend confusion when they are included in a claim. Claim 12 depends from claim 11 and does not rectify the indefiniteness, so it must also be rejected under 35 U.S.C. 112(b).
Claim 16 is indefinite for reciting exemplary language, specifically “optionally” at line 5. The word “optionally” here is not operating to identify an alternative to the enumerated dosages; it functions to give a preference for the upper bound of the dosage. See MPEP 2173.05(d). Examples and preferences lend confusion when they are included in a claim. Claim 32 suffers a similar deficiency at lines 4 and 8 and is also indefinite.
Claim 16 refers to “a therapeutic equivalent concentration to a concentration of SF-4 (heparastatin) of at least 10 nM, . . . and, optionally, no greater than 5 mM.” It is unclear what the basis for “equivalence” is. Claim 16 might be requiring that the concentration of the heparanase inhibitor be present at the enumerated concentrations or it might be requiring that it be present at a concentration that is equivalent in some way to a concentration of SF-4. Claim 32 suffers a similar deficiency and is also indefinite.
Claim 17 refers to graft tissue “such as lung tissue or a lung.” Examples and preferences lend confusion when they are included in a claim. It is unclear whether claim 17 is limited to lung tissue. See MPEP 2173.05(d).
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, 2, 6, 8, 9, 11, 13, 14, 16-19, 23, 25, 26, 28, and 30-32 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.
Claim 1 is drawn to a method that comprises contacting graft tissue with “an amount of a heparanase inhibitor effective to reduce transplant rejection of the tissue” after implantation. Claim 18 is drawn to a method for transplanting graft tissue comprising implanting the tissue, then contact it with “an amount of a heparanase inhibitor effective to reduce transplant rejection of the tissue.” Claims 2 and 19 list various heparanase inhibitors or “pharmaceutically acceptable salt[s] or isostere[s]” of them. The skilled artisan would not have concluded that applicant possessed the claimed “effective amount” of all heparanase inhibitors. The skilled artisan would also not have concluded that applicant possessed the effective amount of isosteres of those inhibitors.
Before the effective filing date, Ziolkowski et al. (2012, Journal of Clinical Investigation 122: 132-141; reference U on PTO-892) teaches the heparanase inhibitor PI-88 is preventative for type 1 diabetes in NOD mice because it protects islets from radical oxygen species (ROS). (Page 135.) Cassinelli et al. (2020, “Non-Anticoagulant Heparins as Heparanase Inhibitors,” in Heparanase: From Basic Research to Clinical Applications, Vlodasky et al., eds.; reference V on PTO-892) reviews other applications for heparanase inhibitors. Cassinelli identifies heparanase inhibitors as useful antiviral agents (section 20.7.1 at page 511), anti-inflammatory agents (section 20.7.5 at page 513), and anti-cancer agents (section 20.7.3 at page 512). Barash et al. (2021, Cancers 13: 2959; reference W on PTO-892) teaches the heparanase inhibitor 4-MMI as useful for attenuating primary tumor growth and metastasis as well as for treating colitis, pancreatitis, diabetic neuropathy, tissue fibrosis, and viral infections involving heparanase. (Abstract.) Before the effective filing date, however, the art did not recognize a general role for heparinase inhibitors as being protective against transplant rejection when the compounds are contacted with tissue for transplantation. “[F]or inventions in emerging and unpredictable technologies, or for inventions characterized by factors not reasonably predictable which are known to one of ordinary skill in the art, more evidence is required to show possession.” MPEP 2163(II)(A)(3)(a)(1).
The skilled artisan would not have concluded that applicant possessed an effective amount of every heparanase inhibitor that would protect transplantable tissue from immune rejection upon implantation. Applicant provides a single working example in which rat lungs are placed on ex vivo lung perfusion (EVLP) for an undisclosed time with an unidentified amount of the agent heparostatin (SF4), then transplanted into recipients. (Paragraph 131.) Applicant observed reduced signs of transplant rejection compared to lungs not treated with SF4. (Paragraph 131.) The specification does not, however, provide sufficient disclosure such that the skilled artisan would identify an “effective amount” of SF4, much less an “effective amount” of every other heparanase inhibitor.
Beyond the issue with “effective amounts” of the enumerated heparanase inhibitors in claims 2 and 19, the claims also include embodiments that provide effective amounts of isosteres of those compounds. An “isostere” is one of two or more substances (as carbon monoxide and molecular nitrogen) that exhibit similarity of some properties as a result of having the same number of total or valence electrons in the same arrangement and that consist of different atoms and not necessarily the same number of atoms. (See definition from Merriam-Webster, https://www.merriam-webster.com/medical/isostere, at reference X on PTO-892.) This limitation opens the scope of the claim to all compounds that have the same number of valence electrons and the same general arrangement but not the claimed structures. The skilled artisan considering applicants’ disclosure in light of the prior and contemporaneous art would not have envisaged all isosteres of the enumerated heparanase inhibitors and also concluded that applicants possessed the necessary “effective amount” required to achieve the claimed endpoint.
Claims 16 and 32 refer to administering “a therapeutic equivalent concentration to a concentration of SF-4 (heparastatin) of at least 10 nM, . . . and, optionally, no greater than 5 mM.” As discussed above, the specification does not identify the amount of SF4 that provides the desired outcome, so the skilled artisan would not have concluded that applicants possessed amounts of other heparanase inhibitors that are “equivalent” to some concentration of SF4.
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, 2, 8, 9, 11, 13, 17-19, 23, 25, 26, 28, and 30 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Simeonevic et al. (US 20110104173; on 11/25/24 IDS). Simeonevic qualifies as prior art under section 102(a)(1) outside the one-year grace period of 35 U.S.C. 102(b). This rejection addresses the embodiment in which the heparanase inhibitor is PI-88 and is contacted with the transplanted tissue within the recipient of the tissue.
Simeonevic teaches that heparanase plays a role in islet allograft rejection; specifically, heparanase inhibitors such as PI-88 can delay the immune destruction of islet allografts in conventional mice and protect islet isografts in autoimmune diabetic NOD hosts. (Paragraph 72.) Simeonevic exemplifies administering PI-88 to prediabetic NOD mice and observes lack of autoimmune destruction of transplanted beta-islets in treated mice. (Paragraphs 145-146, 151-152.) Regarding claims 11 and 28, Simeonevic administers 10mg PI-188 per kg per day, which equates to approximately 4.167[Symbol font/0x6D]M assuming a molecular weight for PI-188 of 2,400 Da. Regarding claims 13 and 30, Simeonevic administers PI-188 daily (every 24 hours) intraperitoneally. Regarding claim 17, Simeonevic’s treated islets are graft tissue prepared according to the method of claim 1; claim 17 does not require that the graft tissue be isolated from its source animal.
Claims 1, 2, 6, 9, 11, 13, 14, 17-19, 23, 26, 28, 30, and 31 are rejected under 35 U.S.C. 102(a)(1) as anticipated by Noda et al. (2021, Scientific Reports 11:12265; on 11/25/24 IDS). Noda was published online on 6/10/21 and is therefore prior art outside the section 102(b) grace period (see Priority discussion above). This rejection addresses the embodiment in which the heparanase inhibitor is heparin or N-acetyl heparin (a “chemical derivative of heparin”) and is contacted with the transplanted tissue within the donor of the tissue.
Noda teaches administering heparin or N-acetyl heparin (NAH) intravenously to rats through the jugular vein in order to perfuse the lung tissue. (Page 9, second full paragraph.) Noda then procures the lungs from the treated rats and performs ex vivo lung perfusion. (Page 9, third full paragraph.) Noda administers 300[Symbol font/0x6D]g of heparin or NAH in 300[Symbol font/0x6D]L saline, addressing the requirements of claims 11 and 28. Noda teaches performing the infusion for at least one hour after induction of ischemia, addressing the timing requirements of claims 13 and 30. Noda teaches transplanting the perfused lungs and assaying endothelial glycocalyx (eGC) shedding and endothelial damage, finding that inhibition of heparanase with heparin or NAH maintained both syndecan-1 staining and endothelial barrier integrity relative to untreated lungs. (Page 5.)
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Lora E Barnhart Driscoll, whose telephone number is (571)272-1928. The examiner can normally be reached M-F 7:00-4:00 p.m. ET.
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/Lora E Barnhart Driscoll/Primary Examiner, Art Unit 3991
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