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 .
Election/Restrictions
Applicant’s election without traverse of an outcome of increasing oxygen delivery in a subject and the compositions comprising HEPES buffered saline and dextrose with liposomes encapsulating the calcium salt of trans-crocetin in a pegylated liposome comprising hydrogenated soy phosphatidyl choline (HSPC), cholesterol and PEG-1,2-distearoyl-sn-glycero-3-phosphoethanolamine (DSPE), a diameter of 80 – 150 nm, anionic, and a zeta potential of -1 to -25 mV in the reply filed on May 11, 2026 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
The Examiner did not locate the elected size range in the claims or even in the specification, although a range of 80 – 120 nm was located in claim 195 that is supported by the disclosure as filed.
Drawings
The drawings are objected to because the quality of the structures drawn in the figures is not sufficiently high to prevent issues with quality should this application processed to allowance. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claim 196 is objected to because of the following informalities: abbreviations are present that are not spelled out the first time they appear such as in parts [m] and [n] of this claim. Appropriate correction is required.
Claim Rejections - 35 USC § 112 – Scope of Enablement
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, 188 – 192, 195 – 205 and 209 – 211 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for increasing the oxygen partial pressure in the blood stream and for the treatment of conditions known in the art that can be treated by trans-crocetin, does not reasonably provide enablement for increased oxygen delivery, the prevention of diseases or conditions or the treatment of conditions that are not known to be treatable by trans-crocetin administration. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The disclosure and claims of the application have been compared per the factors indicated in the decision In re Wands, 8 USPQ2nd 1400 (Fed. Cir. 1988) as to undue experimentation
The factors include:
1. The nature of the invention;
2. The breadth of the claims;
3. The predictability or unpredictability of the art;
4. The amount of direction or guidance presented;
5. The presence or absence of working examples
6. The quantity of experimentation necessary;
7. The state of the prior art; and
8. The relative skill of those skilled in the art.
Each relevant factor is addressed below on the basis of comparison of the disclosure, the claims and the state of the art in the assessment of undue experimentation.
The nature of the invention; the breadth of the claims:
The claims require administration of a composition comprising trans-crocetin at a dosage of 2 – 10 mg/kg to a subject in need. The preamble recites that the method is to increase delivery of oxygen in the subject or to treat or prevent a disease or condition. The disease or condition encompasses any possible disease or condition that can arise. Between the recitation of prevention and what appears to be a general need for more oxygen delivery, the patient population to whom the trans-crocetin is administered is not limited by the independent claim.
The predictability or unpredictability of the art; the amount of direction or guidance presented; the presence or absence of working examples; the quantity of experimentation necessary; the state of the prior art; the relative skill of those skilled in the art:
The relative skill of those skilled in the art is high such as medical doctor. Trans-crocetin is known in the art to increase the partial pressure of O2 in the blood (abstract of US 3,975,519) and has antioxidant activity, cardiovascular protection and skin cancer suppression effects (¶ [0002] of US 2021/0331997; English language equivalent of CN109180469).
The specification provides numerous examples of the preparation of liposomes comprising trans-crocetin although there are some data set forth for patients administered the compositions. Example 7 (p 214 of specification as filed onward) administered liposomes comprising trans-crocetin to patient with severe acute respiratory distress syndrome and receiving artificial respiratory support due to COVID-19. Figure 15 shows the PaO2/FiO2 (partial pressure of arterial oxygen/fraction of inspired oxygen) over time increased in the subjects using the dosing regimen set forth in ¶ [0485] of the specification as filed. No other experimental results such as relating to the treatment or prevention of other conditions was located in the disclosure as originally filed.
Trans-crocetin is known in the art and demonstrated in the specification as filed to increase the partial pressure of oxygen in the blood stream and to have antioxidant activities. Such antioxidant activities could have therapeutic effects on some conditions and several are set forth in the prior art, but the claims encompass the prevention or treatment of any disease or condition. Nothing in the art appreciated therapeutic effects would indicate activity towards a condition such as diabetes which would require effects on insulin levels and/or insulin activity or antibacterial effects that would prevent or treat bacterial infections. Therefore undue experimentation would be required to enable the full scope of the instant claims to determine which diseases or conditions could be prevented and/or treated by the administration of trans-crocetin within the claimed dosage range.
Claim Rejections - 35 USC § 112 – Indefiniteness
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 195 - 200, 203 and 204 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.
Each claim contains at least one instance of “e.g.” which means “for example” that renders the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 196 also contains several instances of "such as" that renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Please clarify.
Claims 189 – 192 and 195 – 204 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. Each claim contains the phrase “any range contained therein” which is not clear and would appear to encompass infinite ranges as any number falling within any of the explicitly recited ranges could serve as an end point for a range. This broadens the scope of the claim to such an extent that the metes and bounds cannot be determined. Please clarify.
Claim 196 is 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 196 recites subsections [a] – [an] as alternative limitations, the vast majority referring in the alternative to all of the previous subsections. For example, subsection [g] begins with “the aqueous solution according to any one of [a] – [f] and subsection [h] begins with “the aqueous solution according to any one of [a] – [g]”. The sheer number of possible alternatives means that the metes and bounds of this claim cannot be determined.
Please clarify.
Rewriting each subsection as a separate claim in the current format would result in numerous improper multiple dependent claims as no multiply dependent claim can depend on any other multiple dependent claim (see MPEP 608.01(n)(I)).
Claim 210 is 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 210 recites the limitation "the pharmaceutical composition" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 103
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.
Claim(s) 1 and 191 are rejected under 35 U.S.C. 103 as being unpatentable over Gainer (US 3,975,519).
Gainer discloses a method for increasing the partial pressure of oxygen (O2) in the blood of a mammal by administering an effective dose of a water soluble carotenoid (whole document, e.g., abstract). The treatment can provide relief for the treatment of cystic fibrosis, asthma, emphysema and intensive care units where oxygen tents are used (col 2, ln 26 – 33). 8,8’diapo-8,8’-carotenic acid or crocetin is one of two most preferred compounds (col 3, ln 9 – 10) of the formula shown at col 2, ln 55 useful for this purpose and that indicates that preferred compound is trans-crocetin. The carotenoid can be used in an injectable form (col 3, ln 21). Water soluble carotenoids have been found to increase the diffusivity of oxygen through aqueous medium (col 1, ln 15 – 17) and increase the partial pressure of oxygen in the bloodstream after intravenous injection and could also be taken orally (col 3, ln 12 – 18). Significant increases in oxygen partial pressure in the blood were observed 15 – 20 minutes after injection of crocetin-saline in the ear vein of New Zealand white male rabbits (col 3, ln 33 – 36 and col 4, ln 5 – 24). The animal or human is treated with preferably 0.001 to 100 mg of active ingredient per kilogram of body weight per each application (col 3, ln 25 – 27) with dosages in mg/kg/day and mg/kg/week disclosed at col 3, ln 18 – 20 and 27 – 31).
The example administered 0.3 mg (10 mL of 30 µg/mL solution) of crocetin to 4 kg rabbits which is 0.075 mg/kg, lying outside the claimed range and therefore fail to anticipate the instant claims.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to optimize the administered dose of trans-crocetin within the range disclosed by Gainer to increase the delivery of oxygen. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because Gainer discloses the increase in oxygen partial pressure in the blood upon administration of trans-crocetin to a subject. The amount of therapeutic agent administered to a subject is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of the therapeutic agent to administer in order to best achieve the desired results. Factors including age, weight, overall health, condition being treated, severity of the condition being treated and dosing schedule can alter the optimal dosing for a subject. The claimed values lie within the range disclosed by Gainer and there is no evidence of record as to the criticality of the claimed dosage range.
Claim(s) 188 – 190, 192, 196, 197 – 203, 209 and 210 are rejected under 35 U.S.C. 103 as being unpatentable over Gainer as applied to claims 1 and 191 above, and further in view of CN101811956 (CN’956, complete machine translation accompanies this Office Action).
Gainer is discussed above.
The presence of the trans-crocetin in a liposome is not disclosed.
CN’956 discloses the preparation of saffron acid from the carotenoid family (¶ [0004]). Liposomes of trans-saffron acid can further improve cellular lipidation (p 41 of translation, last ¶). Note the discussion in ¶ [0037] indicating that trans-saffron acid and trans-crocetin are used interchangeably in this document. Cellular level experiments have demonstrated that trans-crocin and liposomes containing trans-crocin have significant antioxidant activity and the effect of preventing and treating fatty liver (¶ [0028]). When trans-saffron acid was treated with liposomes, the decrease in TG was significantly greater than that of trans-saffron acid alone, and the difference was even more pronounced at low concentrations (¶ [0082]). When trans-saffron acid was treated with liposomes, the decrease in ROS was greater than that in the trans-saffron acid intervention group alone, and the difference was more obvious at low concentrations (¶ [0084]). Decreases in MDA, a product of lipid peroxidation that can promote free radical chain reactions that is an indirect reflection of the degree of oxidative damage to cells was also observed upon administration of saffron acid (p 45 of translation).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to administer trans-crocetin in a liposomal form to increase the oxygen partial pressure in a subject. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because Gainer discloses that non-liposomal trans-crocetin has such an effect in biological systems and CN’956 indicates that liposomes comprising trans-crocetin show increased biological effects compared to non-liposomal trans-crocetin, reasonably suggesting that such encapsulation would have similar increased effects on oxygen partial pressure in the blood stream when administered to a subject. Cystic fibrosis, asthma, emphysema are chronic health conditions and therefore subjects with these conditions can be in continued need to increased oxygen partial pressure on an ongoing basis. That would require administration of trans-crocetin over extended periods of time and not just a single administration. One of ordinary skill in the art would take this into account when determining not only the dose to be administered and the frequency of administration but also the length of administration of the trans-crocetin containing formulation that will determine the number of doses administered. There is no evidence of record as to the criticality of the claimed dosage parameters such as timing of dosing and number of doses administered to a subject.
Claim(s) 195, 196, 204 and 205 are rejected under 35 U.S.C. 103 as being unpatentable over Gainer and CN’956 as applied to claims 1, 188 –192, 196, 197 – 203, 209 and 210 above, and further in view of Lockwood et al. (US 2007/0015735) and Garbuzneko et al. (Langmuir, 2005).
Gainer and CN’956 are discussed above.
Elected features such as size and zeta potential of the liposomes and constituents of the liposomes such as the elected are not disclosed by either reference.
Lockwood et al. discloses carotenoid, analogs or derivatives thereof (whole document, e.g., abstract). The ordinary practitioner in the art would appreciate that pharmaceutical compositions, pharmaceutical formulations or pharmaceutical preparations encompass includes pharmaceutically acceptable salts of the compound (¶ [0094], and amongst such pharmaceutically acceptable salts is calcium (¶ [0095]).
Garbuzneko et al. discloses the electrostatics of large unilamellar vesicles (LUVs) in various lipid concentrations that were correlated with steric stabilization (whole document, e.g., abstract). Studies liposomes comprised a phosphatidylcholine such as HSPC, cholesterol and a mPEG (methyl polyethylene glycol) lipid such as mPEG-DSPE in various amounts (see table 1). A unimodal liposome size distribution of a mean of 110 ± 10 nm was determined by dynamic light scattering (section 3.3.2). mPEG-DSPE is a negatively charged lipid whose progressive addition to the liposomes was found to increase the negative surface potential (abstract).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to prepare liposomes using materials such as those disclosed by Garbuzneko et al. that can have a negative zeta potential and size falling within the elected range and the trans-crocetin can be provided as a pharmaceutically acceptable salt. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because liposomes loaded with trans-crocetin are disclosed by CN’956 but the components are not disclosed and materials such as PEG-DSPE, cholesterol and HSPC can be used to prepare liposomes. Pharmaceutically acceptable salts of carboxylic acid containing compounds are known to those of ordinary skill in the art. Such an artisan can determine the appropriate liposome composition (e.g., ingredients, size and zeta potential) and the salt form of the therapeutically effective compound to include in the formulation. There is no evidence of record as to the criticality of these features.
Claim(s) 196 and 211 are rejected under 35 U.S.C. 103 as being unpatentable over Gainer, CN’956, Lockwood et al. and Garbuzneko et al. as applied to claims 1, 188 –192, 196, 197 – 203, 209 and 210 above, and further in view of Webb et al. (US 2005/0118249).
Gainer, CN’956, Lockwood et al. and Garbuzneko et al. are discussed above.
HEPES buffer and dextrose as part of the liposomal formulation and the loading method of claim 211 are not disclosed.
Webb et al. discloses Liposomal compositions which have enhanced retention properties for biological agents (whole document, e.g., abstract). The liposomes can be provided in HBS (HEPES buffered saline; e.g., the description of Figure 6A). Dextrose can also be a pharmaceutically acceptable carrier to be used when compositions are administered intravenously (¶ [0079]). Loading methods a pH gradient across the lipid bilayer that results in the uncharged species crossing the membrane that is then charged and while and while neutral exterior buffer and acidic interior buffer are known, other method os establishing pH gradients are known (¶ [0007]). Organic acids such as gluconic acid, tartaric acid or citric acid can be present in the acidic loading buffers (¶ [0067]).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to use carriers for the liposomes such as those that can contain HBS and/or dextrose and to load the active agent in the liposome after liposome formation. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because liposomal formulations can be administered in pharmaceutically acceptable carrier such as those disclosed by Webb et al. that include HBS and dextrose. The selection of such carriers from those that are known in the art is well within the skill of one of ordinary skill in the art. Liposomes can be loaded with therapeutic agents after liposome formation and one of ordinary skill in the art knows of such methods based on the prior art and their knowledge. The selection of the exact method by which the liposomes are loaded with therapeutic agent does not patentably distinguish the instant claims over the prior art.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
Claims 1, 188 – 192, 195 – 205 and 209 – 211 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 197 – 190, 193 – 199 and 201 - 208 of copending Application No. 18/018,132 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of US’132 recite a method of increasing the delivery of oxygen or treating or preventing a disease or condition in a subject, which comprises administering an effective amount of a fixed dose of 200 – 900 mg trans-crocetin, or any range therein between, to a subject in need thereof (claim 197). The trans-crocetin can be liposomal form with various characteristics (e.g., claim 193). The dosage is given in mg, not mg/kg as in the instant claims. For the range of 200 – 900 mg to at least overlap with the instantly claimed range of 2 – 10 mg/kg, subjects must weigh between 20 kg and 450 kg, a range which encompasses adults humans and therefore the claims of US’132 and the instant claims are not patentably distinguished as carrying out the method of US’132 with human adults.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 188 – 192, 195 – 205 and 209 – 211 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 187 - 207 of copending Application No. 18/018,205 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of US’205 recite a method of increasing the delivery of oxygen or treating or preventing a disease or condition in a subject, which comprises administering an effective amount of one or more fixed dose of 50 mg to 900 mg liposomal trans-crocetin, or any range therein between, to a subject in need (claim 187). Various characteristics of the liposomal formulation as required by the instant claims are recited in the dependent claims. The dosage is given in mg, not mg/kg as in the instant claims. For the range of 50 – 900 mg to at least overlap with the instantly claimed range of 2 – 10 mg/kg, subjects must weigh between 5 kg and 450 kg, a range which encompasses many children and humans and therefore the claims of US’205 and the instant claims are not patentably distinguished as carrying out the method of US’205 with humans.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 188 – 192, 195 – 205 and 209 – 211 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 123 - 141 of copending Application No. 19/333,941 in view of Gainer (US 3,975,519). The claims of US’941 recite pegylated-liposomal compositions comprising a trans-carotenoid salt (claim 123) and various methods in which the composition is administered to subjects such as a treating or preventing a lung condition (claims 136 and 137) or those characterized by ischemia, hypoxia or nitric oxide deficiency (claim 128 and 139). The subjects of such methods fall within the scope of the patient population of the instant claims.
The dose of the pegylated-liposomal compositions comprising a trans-carotenoid salt is not claimed.
Gainer is discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate optimize the dose of the therapeutic agent administered to a subject in the claims of US’941. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the amount of therapeutic agent administered to a subject is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of the therapeutic agent to administer in order to best achieve the desired results. Factors including age, weight, overall health, condition being treated, severity of the condition being treated and dosing schedule can alter the optimal dosing for a subject. Cystic fibrosis, asthma, emphysema are chronic health conditions and therefore subjects with these conditions can be in continued need to increased oxygen partial pressure on an ongoing basis. That would require administration of trans-crocetin over extended periods of time and not just a single administration. One of ordinary skill in the art would take this into account when determining not only the dose to be administered and the frequency of administration but also the length of administration of the trans-crocetin containing formulation that will determine the number of doses administered. There is no evidence of record as to the criticality of the claimed dosage parameters such as timing of dosing and number of doses administered to a subject.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 188 – 192, 195 – 205 and 209 – 211 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 4, 6 – 11, 29, 31 32, 35, 45, 50, 51, 58, 59, 80, 81 and 109 of copending Application No. 19/339,809 in view of Gainer (US 3,975,519). The claims of US’809 recite a composition comprising liposomes encapsulating a carotenoid as defined in claim 1 that can be trans-crocetin with a multivalent cation (claim 6). Features of the liposomes as required by the instant claims are claimed (e.g., claims 21, 32 and 35). Methods for treating or preventing a disease in a subject in need thereof are also present and can be characterized by ischemia, hypoxia or nitric oxide deficiency (claims 80 and 81).
The dose of the liposomal compositions comprising a carotenoid is not claimed.
Gainer is discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate optimize the dose of the therapeutic agent administered to a subject in the claims of US’809. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the amount of therapeutic agent administered to a subject is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of the therapeutic agent to administer in order to best achieve the desired results. Factors including age, weight, overall health, condition being treated, severity of the condition being treated and dosing schedule can alter the optimal dosing for a subject. Cystic fibrosis, asthma, emphysema are chronic health conditions and therefore subjects with these conditions can be in continued need to increased oxygen partial pressure on an ongoing basis. That would require administration of trans-crocetin over extended periods of time and not just a single administration. One of ordinary skill in the art would take this into account when determining not only the dose to be administered and the frequency of administration but also the length of administration of the trans-crocetin containing formulation that will determine the number of doses administered. There is no evidence of record as to the criticality of the claimed dosage parameters such as timing of dosing and number of doses administered to a subject.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 188 – 192, 195 – 205 and 209 – 211 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 186 of copending Application No. 19/640,753 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of US’753 recite methods of treatment of increasing the delivery of oxygen in a subject (claim 1) or numerous other indications such as treating acute respiratory distress syndrome (claim 7) by the administration of an effective amount of trans-crocetin. The subjects of such methods fall within the scope of the patient population of the instant claims. The trans-crocetin can be in liposomal form (e.g., claims 28 – 31) with various characteristics as required by the instant claims (e.g., claim 36). Claim 38 recites dosages in mg/kg including a range of 2 – 20 mg/kg as recited in the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 188 – 192, 195 – 205 and 209 – 211 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 39 of U.S. Patent No. 12,458,597 in view of Gainer (US 3,975,519). The claims of US’597 recite pegylated-liposomal compositions comprising a trans-carotenoid salt with a multivalent cation counterion (claim 1) and methods for preparing such a composition (claims 24 and 28 - 32). Various features of the liposome as required by the instant claims are also claimed (e.g., claims 7 – 11). Methods for treating or preventing a disease in a subject needing such treatment or prevention are also present including lung diseases or conditions (claims 21 – 23). The subjects of such methods fall within the scope of the patient population of the instant claims.
Dosages of the trans-carotenoid are not claimed other than effective amounts.
Gainer is discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate optimize the dose of the therapeutic agent administered to a subject in the claims of US’597. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the amount of therapeutic agent administered to a subject is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of ordinary skill to determine the optimal amount of the therapeutic agent to administer in order to best achieve the desired results. Factors including age, weight, overall health, condition being treated, severity of the condition being treated and dosing schedule can alter the optimal dosing for a subject. Cystic fibrosis, asthma, emphysema are chronic health conditions and therefore subjects with these conditions can be in continued need to increased oxygen partial pressure on an ongoing basis. That would require administration of trans-crocetin over extended periods of time and not just a single administration. One of ordinary skill in the art would take this into account when determining not only the dose to be administered and the frequency of administration but also the length of administration of the trans-crocetin containing formulation that will determine the number of doses administered. There is no evidence of record as to the criticality of the claimed dosage parameters such as timing of dosing and number of doses administered to a subject.
Claims 1, 188 – 192, 195 – 205 and 209 – 211 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 26 of U.S. Patent No. 12,622,874. The claims of US’874 recite a of increasing the delivery of oxygen in a subject comprising administering an effective amount of one or more dose(s) of 2 mg/kg to 10 mg/kg liposomal trans-crocetin, or any range therein between, to a subject in need thereof with the trans-crocetin being in a salt form with a one of the claimed counterions (claim 1). Various features of the liposomes as required by the instant claims are also claimed (claims 21 and 25).
Conclusion
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/Nissa M Westerberg/Primary Examiner, Art Unit 1618
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