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 .
Status of the Clams
Claims 1-10, 12, and 26-28 responsive to communications on 03/02/2023 are pending.
Claims 1-10, 12, and 26-28 have been examined on their merits.
Specification
The disclosure is objected to because of the following informalities: the specification misspells Wharton’s colloid (also referred to as Wharton’s jelly in the art) as “Walton colloid” in numerous locations (paragraphs [0015, 0027, etc.]). This appears to be the result of a transliteration error from the original Japanese into English.
Appropriate correction is required.
Claim Objections
Claim 3 is objected to because of the following informalities: the claim recites the term “Walton-colloid” which is a misspelling of the term Wharton’s colloid (Wharton’s jelly). Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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 1-9, 12, and 26-28 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for:
A method for treating a cranial nerve disorder, or delaying or alleviating the onset thereof, comprising administering a pharmaceutical composition comprising a culture supernatant of tissue cells derived from fetal appendage as an active ingredient to a subject in need thereof.
does not reasonably provide enablement for:
A method for treating a cranial nerve disorder, or preventing, delaying or alleviating the onset thereof, comprising administering a pharmaceutical composition comprising a culture supernatant of tissue cells derived from fetal appendage as an active ingredient to a subject in need thereof.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
SCOPE OF THE INVENTION
The breadth of the claims encompasses a method for preventing the onset of a cranial nerve disorder. The claim implies that a method of administering a pharmaceutical composition comprising a culture supernatant of tissue cells derived from fetal appendage as an active ingredient to a patient is sufficient to prevent the onset of a cranial nerve disorder (and thus, prevent the cranial nerve disorder).
As discussed supra, the specification fails to describe a method of preventing the onset of a cranial nerve disorder by administering a pharmaceutical composition comprising a culture supernatant of tissue cells derived from fetal appendage as an active ingredient to a patient and would require undue experimentation to discover methods for preventing the onset of a cranial nerve disorder.
The specification only discloses and provides guidance for treating a cranial nerve or delaying or alleviating the onset thereof.
The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The Court in Wands states: “Enablement is not precluded by the necessity for some 'experimentation.'” Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. “Whether undue experimentation is needed is not a single simple factual determination, but rather is a conclusion reached by weighing many factual considerations.” (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims. While all of these factors are considered, a sufficient amount for a prima facie case is discussed below.
The office has analyzed the specification in direct accordance to the factors outlined in In re Wands. MPEP 2164.04 states: "[W]hile the analysis and conclusion of a lack of enablement are based on factors discussed in MPEP 2164.01(a) and the evidence as whole, it is not necessary to discuss each factor in written enablement rejection." These factors will be analyzed, in turn, to demonstrate that one of ordinary skill in the art would have had to perform "undue experimentation" to make and/or use the invention and therefore, Applicant's claims are not enabled commensurate with the scope of the invention.
ACTUAL REDUCTION TO PRACTICE
The specification does not provide guidance for or a working example for a method of administering a pharmaceutical composition comprising a culture supernatant of tissue cells derived from fetal appendage as an active ingredient to a patient is sufficient prevent the onset of a cranial nerve disorder.
Instead, the specification only demonstrates that in a hypoxic reperfusion pediatric cerebral palsy model (Example 4, paragraphs [0089-0091]), mice treated with MSC culture supernatant demonstrated improved spontaneous behavior over time as compared to non-treated mice (Figs. 3 and 4). Furthermore, as compared to controls (healthy mice), neither treated or untreated groups demonstrated significant results after 2 or 4 weeks (Fig, 4).
Thus, applicant does not demonstrate that the method can prevent the onset of a cranial nerve disease.
The lack of working examples that demonstrate the prevention of the onset of a cranial nerve disease necessitates further experimentation.
Therefore, the specification does not provide sufficient guidance on how to perform a method for preventing a cranial nerve disease by administering a pharmaceutical composition comprising a culture supernatant of tissue cells derived from fetal appendage as an active ingredient to a patient.
STATE OF THE ART & QUANTITY OF EXPERIMENTATION
As evidenced by Anoutaleb et al. (Journal of Chemical Neuroanatomy, 2019 on IDS 07/26/2024), methods comprising administering conditioned media (a pharmaceutical composition) derived from the supernatant of amniotic MSCs (thus, tissue cells derived from a fetal appendage) to rats (subjects) following cerebral ischemia reperfusion injury to provide neuroprotective effects including activating neuronal ERK1/ERK2-BDNF signaling pathway, neurogenesis, angiogenesis as well as suppression of apoptosis (Abstract, p1) where known in the art. However, Anoutaleb is silent as to the prevention of the onset of cranial nerve diseases specifically.
This is confirmed by Ueda et al. (US20150203821A1, 2015, on IDS 07/26/2024), who evidences that methods for treating central nerves system diseases in Creutzfeldt Jakob disease (as identified in the instant specification as a cranial nerve disease) comprising administering a pharmaceutical composition comprising a culture supernatant to a subject (“culture sup”) derived from umbilical cord MSCs (paragraphs [0100, 0024-0027]), but does not demonstrate preventing a cranial nerve disease.
This is further confirmed by Messina et al. (US20140154226A1, 2014) who evidences methods for treating a patient with neurodegenerative condition (a subject in need) comprising administering to the patient an effective amount a pharmaceutical composition comprising conditioned media (supernatant) derived from cells from umbilical cord tissue (a fetal appendage) (claims 20 and 21; paragraphs [0002, 0026]), but does not demonstrate preventing a cranial nerve disease.
As a result, since the prior and art at the effective filing date of the present application did not provide guidance for preventing the onset of a cranial nerve disease by administering ta pharmaceutical composition comprising a culture supernatant of tissue cells derived from a fetal appendage, the physiological art is recognized as unpredictable (MPEP 2164.03). As set forth in In re Fisher, 166 USPQ 18 (CCPA 1970), compliance with 35 USC 112, first paragraph requires: “That scope of claims must bear a reasonable correlation to scope of enablement provided by specification to persons of ordinary skill in the art; in cases involving predictable factors, such as mechanical or electrical elements, a single embodiment provides broad enablement in the sense that, once imagined, other embodiments can be made without difficulty and their performance characteristics predicted by resort to known scientific laws; in cases involving unpredictable factors, such as most chemical reactions and physiological activity, scope of enablement varies inversely with degree of unpredictability of factors involved.” Moreover, the courts have also stated that reasonable correlation must exist between scope of exclusive right to patent application and scope of enablement set forth in the patent application (27 USPQ2d 1662 Ex parte Maizel). In view of the foregoing, due to the lack of sufficient guidance provided by the specification regarding the issues set forth above, the state of the relevant art, and the breadth of the claims, it would have required undue experimentation for one skilled in the art to make and use the instant broadly claimed invention.
CONCLUSION
In conclusion, since the art does not provide guidance for preventing the onset of a cranial nerve disease and is highly unpredictable with respect to performing this method, and since the specification does not provide ample guidance with respect to achieving the unexpected results, one would be burdened with undue experimentation to perform the claimed invention in order to prevent the onset of a cranial nerve disease.
In conclusion, given the breadth of the claims and the limited scope of the specification, an undue quantity of experimentation is required to make and use the invention beyond the scope of a method of treating a cranial nerve disorder, or delaying or alleviating the onset thereof, comprising administering a pharmaceutical composition comprising a culture supernatant of tissue cells derived from fetal appendage as an active ingredient to a subject in need thereof as discussed above.
Claims 2-9, 12, and 26-28 are rejected under 35 USC 112(a) for their dependency on claim 1.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1-5, 8-10, and 26-28 are rejected under 35 U.S.C. 102(a)(1) or 35 U.S.C. 102(a)(2) as being anticipated by Messina et al. (US20140154226A1, 2014) as evidenced by Anthony et al. (Cureus, 2019).
In regards to claims 1-2, 8-9, and 26, Messina discloses methods for treating a patient with a neurodegenerative condition (a subject in need) comprising administering to the patient an effective amount of a pharmaceutical composition comprising conditioned media (supernatant) derived from cells from umbilical cord tissue (a fetal appendage) (claims 20 and 21; paragraphs [0002, 0026]). As the effective amount of the pharmaceutical composition as disclosed by Messina is the treating agent, a person of ordinary skill in the art would have recognized that it is the active ingredient.
In regards to the effect of the preamble, in regards to the intended use as a method for treating a cranial nerve disorder (see MPEP 2111.02), Messina discloses that the method can treat Creutzfeldt-Jakob disease (paragraph [0043], a non-hereditary prion disease), which claim 26 indicates is a cranial nerve disorder. Additionally, as evidenced Anthony, Creutzfeldt-Jakob disease is involved in cranial nerve palsies (Abstract, p1), and therefore, the method of Messina is at least capable of perming this intended use.
In regards to claim 3, Messina discloses that the umbilical cells, express mesenchymal stem cell (MSC) markers (claim 6; paragraph [0071]), and therefore, appear to be in fact umbilical MSCs.
In regards to claim 4, Messina discloses that the conditioned medium comprises cytokines (paragraph [00040]).
In regards to claim 5, Messina discloses that the cultured umbilical cells secrete IL-6 (paragraph [0074, 0118]) and that the pharmaceutical composition can comprise IL-6 (paragraph [0101]).
In regards to claim 10, Messina discloses that the conditioned media (the cranial nerve therapeutic agent) is obtained (recovered) from media that postpartum cells (fetal appendage cells) were grown in (paragraph [0026]).
In regards to claims 27 and 28, whether the pharmaceutical composition regenerates cranial nerves as in claim 27 or survival and proliferation of the specific cells as in claim 28, these are properties of the method steps as in claim 1 and describe natural effects that would occur if the method were performed.
In the instant case, because Messina discloses that the pharmaceutical composition regenerates neural tissue (paragraph [0002]) and because, as above, Messina discloses that the pharmaceutical composition, Messina discloses that the method can treat Creutzfeldt-Jakob disease (paragraph [0043]) which claim 26 indicates is a cranial nerve disorder (and as evidenced by Anthony is involved in cranial nerve palsies (Abstract, p1)), regeneration of cranial nerves as in claim 27 or survival and proliferation of the specific cells as in claim 28 would be the expected result of the method of Messina.
Therefore, Messina anticipates the invention as claimed.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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 6 is rejected under 35 U.S.C. 103 as being unpatentable over Messina et al. (US20140154226A1, 2014) in view of Anoutaleb et al. (Journal of Chemical Neuroanatomy, 2019 on IDS 07/26/2024) as evidenced by Anthony et al. (Cureus, 2019).
Messina anticipates claim 1 as discussed above.
In regards to claim 6, Messina is silent as to the number of days fetal cells were cultured to obtain supernatant.
However, to produce supernatant umbilical cord MSCs for treating neurological ischemia, Aboutaleb discloses that the cells were cultured for 48hrs (Conditioned media collection, p88), which overlaps with the range as in claim 6. A person of ordinary skill in the art would have been motivated to culture cells for this amount of time because Anoutaleb indicates that it is sufficient for obtaining supernatant for achieving neuroprotective effects including activating neuronal ERK1/ERK2-BDNF signaling pathway, neurogenesis, angiogenesis as well as suppression of apoptosis (Abstract, p1). Furthermore, because Anoutaleb teaches that supernatant can be obtained after 48 hours and Messina and Anoutaleb are in the same technical field of using supernatant from fetal tissues to treat neurological diseases, it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Messina and Anoutaleb renders the invention unpatentable as claimed.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Messina et al. (US20140154226A1, 2014) in view of Liu et al. (Biochemical Engineering Journal, 2014) as evidenced by Anthony et al. (Cureus, 2019).
Messina anticipates claim 1 as discussed above.
In regards to claim 7, Messina teaches that fetal cells can be expanded at densities of 5000 cells/cm2 (paragraph [0211]). While this density is reported in cells/cm2, not cells/mL, a person of ordinary skill in the art could have arrived at a concentration of 5 x 104 to 5 x 106/mL by routine optimization, and the disclosure does not point to a criticality in this amount.
In regards to routine optimization, according to MPEP 2144.05(II)(A), generally differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.")
In the instant case because Liu teaches that amniotic fluid stem cells (MSCs) can be cultured to densities of 3.2 x 106 cells/mL (Abstract, p71; Table 3, p77), which overlaps with the range as in claim 7, a person of ordinary skill in the art could have arrived at a density of 5 x 104 to 5 x 106/mL by routine optimization with predictable results and a reasonable expectation of success.
Furthermore, a person of ordinary skill in the art would have been motivated to culture cells at a higher density in order to obtain more conditioned media. Additionally, because as above, Liu teaches that amniotic fluid stem cells (MSCs) can be cultured to densities of 3.2 x 106 cells/mL (Abstract, p71; Table 3, p77), which overlaps with the range as in claim 7, it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Messina and Liu render the invention unpatentable as claimed.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Messina et al. (US20140154226A1, 2014) in view of Jabbehdari et al. (Current Eye Research, published online 05/14/2020) as evidenced by Anthony et al. (Cureus, 2019).
Messina anticipates claim 1 as discussed above.
In regards to claim 12, Messina does not explicitly teach that the pharmaceutical composition is lyophilized.
However, a person of ordinary skill in the art would have been motivated to lyophilize the conditioned media because Jabbehdari teaches lyophilized MSC-derived conditioned media can be stored for extended periods of time, transported conveniently, distributed in consistent concentrations, and readily adjusted for potency (Introduction, p1490). Furthermore, because Jabehdari teaches that conditioned media derived from MSCs can be lyophilized and is as effective as fresh media (Abstract, p1490-1491), it could have been done with predictable results and a reasonable expectation of success.
Therefore, the combined teachings of Messina and Jabbehdari renders the invention unpatentable as claimed.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-10, 12, and 26-28 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8, 10, and 22-24 of copending Application No. 18/003,392 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of both inventions are drawn to methods for treating a cranial nerve defect or methods for producing a cranial nerve disorder therapeutic agent comprising administering a pharmaceutical composition comprising supernatant derived from fetal cells.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH (PAUL) MIANO whose telephone number is (571)272-0341. The examiner can normally be reached Mon-Fri from 8:30am to 5:30pm.
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/JOSEPH PAUL MIANO/Examiner, Art Unit 1631