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 .
Claim Status
Claims 3-5, 7, 8, 10-12, 14-18, 20, 22, 24, 26-34, 37-58, 61-64, 66-68, 70-74, 76, 78, 79 and 81 are cancelled.
Claims 1, 2, 6, 9, 13, 19, 21, 23, 25, 35, 36, 59, 60, 65, 69, 75, 77 and 80 are pending.
Priority
PNG
media_image1.png
130
900
media_image1.png
Greyscale
Claim Objections
Claims 1 and 59 are objected to because of the following informalities: Claims 1 and 59 read in part:
PNG
media_image2.png
128
636
media_image2.png
Greyscale
This seems grammatically awkward and the arrow indicates where the specification [0007] teaches the verb “are” should be.
Claim 25 is objected to because of the following informalities: the placement of “or” is awkward here:
PNG
media_image3.png
88
444
media_image3.png
Greyscale
Appropriate correction is required.
Claim Rejections - 35 USC § 102
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.
Claim(s) 1, 2, 6, 13, 19, 21, 23, 25, 35, 36, 59, 60, 69, 75, 77 and 80 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Arafa et al. (Nature Scientific Reports 2018;8:13674, 16 pages).
Claim interpretation: The limitation of: “free from attached peptide or antigenic moieties or other bioactive materials” is defined in the specification as meaning:
PNG
media_image4.png
396
940
media_image4.png
Greyscale
Regarding claims 1, 2, 6, 13, 59, 60 and 69, Arafa et al. disclose treating thermal burns in a subject in need thereof by administering biodegradable hydroxypropylcellulose with negatively charged gold particles of 28.9-37.65 nm size (average of 33.81 nm) and having a negative zeta potential of -34 mV and negative surface charge (Abstract; Page 5, Burn inductions and establishment of burn wound infections; page 6, Figure 1 and Results Characterization of the AuNPs “The zeta potential of the AuNPs showed a negative surface charge and the mean zeta potential equalled (−34.8 mV) (Fig. 1b).”) The gold particles are free from attached peptide or antigenic moieties or other bioactive materials.
Regarding claim 19, 21, 75 and 77, the composition was applied topically once daily (Page 5, The effects of the AuNPs thermoresponsive gels on the inhibition of wound area). It is the Examiner’s position that topical administration reads on transdermal administration.
Regarding claims 23, 25 and 80, the administration improved one or more symptoms of burn injury (Page 5, The effects of the AuNPs thermoresponsive gels on the inhibition of wound area; Page 9, The effect of the AuNPs thermoresponsive gels on the inhibition of the wound area. “The wounds on all mice that were treated with the prepared formulae, F1 and F2, showed continuous burn edge contraction over the course of treatment.”). The treatment period was 10 days to healing (Page 10, Figure 6) and closed the wound totally thus reducing the size of the burn area by 5%, 10%, 20%, 30% or more compared to a control.
Regarding claim 35, at least skin and tissue regeneration visually occurred (Page 10, Figure 6). The other claimed properties would be inherent in the administration of the negatively charged gold particles upon treating the wound in the natural course of wound healing. See MPEP 2112.01 II.COMPOSITION CLAIMS — IF THE COMPOSITION IS PHYSICALLY THE SAME, IT MUST HAVE THE SAME PROPERTIES
“Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).”
Regarding claim 36, Arafa et al. also administered silver sulphadiazine cream to a burn wound on the same subject (Page 10, Figure 6), where silver sulphadiazine cream is a second therapeutic agent useful to treat burn injury.
Claim(s) 1, 13, 19, 21, 23, 25 and 35 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhao et al. (Am J Transl Res 2018;10(1):246-255).
Regarding claims 1, 13, 19, 21, 25 and 35, Zhao et al. disclose twice daily administration to the thermal burns of a subject in need thereof with negatively-charged, hence a negative zeta potential, aerosol particles improve burn wounds (Title; Abstract; Introduction 1st and 2nd paragraphs; Page 247, Animal experiment). It appears that the aerosol generated is topically applied, which reads on transdermal application. Wound healing is accelerated compared to the control with contraction of the wound edges where at least skin and tissue regeneration visually occurred (Page 247,Figure 1), thus improving one or more symptoms of burn injury. The other claimed properties in claim 35 would be inherent in the negatively charged aerosol particles upon treating the wound in the natural course of wound healing. See MPEP 2112.01 II.COMPOSITION CLAIMS — IF THE COMPOSITION IS PHYSICALLY THE SAME, IT MUST HAVE THE SAME PROPERTIES
“Products of identical chemical composition cannot have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990).”
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 2, 6, 9, 13, 19, 21, 23, 25, 35, 36, 59, 60, 65, 69, 75, 77 and 80 are rejected under 35 U.S.C. 103 as being unpatentable over King et al. (WO2014160465) and Sembrano (US20100034905) and Farina et al. ( International Journal of Inflammation Volume 2013, Article ID 715645, 9 pages) and Heuer et al. (Frontiers in Immunology February 2021; volume 12, articles 614347; 11 pages) and Nam (US20190151266).
Applicant claims, for example:
PNG
media_image5.png
164
834
media_image5.png
Greyscale
PNG
media_image6.png
130
910
media_image6.png
Greyscale
PNG
media_image7.png
88
942
media_image7.png
Greyscale
Level of Ordinary Skill in the Art
(MPEP 2141.03)
MPEP 2141.03 (I) states: “The “hypothetical ‘person having ordinary skill in the art’ to which the claimed subject matter pertains would, of necessity have the capability of understanding the scientific and engineering principles applicable to the pertinent art.” Ex parte Hiyamizu, 10 USPQ2d 1393, 1394 (Bd. Pat. App. & Inter. 1988). The level of skill is that of a burn wound treatment specialist, such an educated artisan will draw conventional ideas from burn wound trauma treatment including methods and materials to treat burns as well as expertise in skin grafting, infection control, and intensive care management.
In addition, the prior art itself reflects an appropriate level (MPEP 2141.03(II)).
Determination of the scope and content of the prior art
(MPEP 2141.01)
Regarding claims 1-2, 6, 35, 59 and 60, King et al. teach a method of increasing the regeneration of damaged tissue in a patient in need thereof, comprising administering a pharmaceutical composition comprising negatively charged particles,
wherein said particles are free from attached peptide or antigenic moieties, and a carrier (Claim 115) and methods of removing pro-inflammatory mediators from the inflammatory milieu in a subject (Claims 38-48), which thereby ameliorates an inflammatory immune response (Claims 49-54) by decreasing inflammatory symptoms [00116, 00153]. King et al. also teach a method of increasing the regeneration of damaged tissue in a patient in need thereof, comprising administering a pharmaceutical composition comprising negatively charged particles, wherein said particles are free from attached peptide or antigenic moieties, and a carrier (Claim 115). No other bioactive agents are present. King et al. teach the administration of negatively charged particles, such as polystyrene, PLGA, or diamond particles, to subjects to ameliorate inflammatory immune responses (Abstract; claims 2-6, 11-12), where PLGA is biodegradable, where the subject has recently experienced physical trauma and the subject has recently experienced an injury ([0025, 00153]; claims 1, 36 and 74) where administration of the particles of the invention increases regeneration of damaged tissue in a subject such as regeneration of epithelial cells [0032], which is epithelialization of claim 35. King et al. teach a negative zeta potential of less than about -100 mV (Claim 7) or between -75 mV and 0 mV (Claim 8), which overlap the claimed ranges of from -100 mV to -1 mV or -80 mV to -30 mV.
Regarding claim 2, King et al. teach liposomal, PEG and cyclodextrin preparations [0065, 0081, 00123, 00127, 00130].
Regarding claim 9 and 65, King et al. teach a particles size between about 0.1 micron and about 10 microns (Claims 13-17), which overlaps the claimed ranges of from 100 nm to 1500 nm., from 100 to 1000 nm or from 400 to 800 nm.
Regarding claims 21 and 77, King et al. teach wherein said composition is administered orally, nasally, intravenously, intramuscularly, ocularly, transdermally, or subcutaneously (Claims 37, 75 and 112).
Regarding claim 35, as noted above King et al. teach regeneration of tissue where it appears that most of the claimed limitations are natural events in the healing process.
Regarding claim 36, King et al. teach administration of one or more therapeutic agents [00118].
Regarding claim 59, King et al. teach carrier particles include biodegradable polymers such as PLA, PGA and PLGA [0067].
Regarding claims 13, 19, 69 and 75, Sembrano teaches methods of treating burns (Title; Abstract) and: “A wound is a defect or break in the skin that comes from physical, mechanical or thermal damage including bums. There are several different types of bums including thermal, chemical, electrical, and radiation induced burns.” [0001]. Sembrano teaches: “The compositions may be administered directed to the skin or bum wound or they may be administered in a bandage or wrap to the skin or burn wound. They may be administered daily, hourly, one, two, three, four, five, six or more times a day, or they may be administered one, two, three, four or more times a week. Those of skill in the art may readily determine the treatment regimen depending upon the concentration of active ingredient and upon the severity and size of the burn wound. The compositions may be administered alone or in combination with other topical compositions either concurrently or sequentially.” [0028]
Regarding claims 1 and 59, Heuer et al. teach that: “Inflammation appears to be of particular importance in the context of thermal injuries…early re-epithelialization is one of the most important positive prognostic markers for an optimal outcome after thermal injury…Neutrophils infiltrate the wound after burn trauma” (Page 2, 2nd paragraph). And: “Activated neutrophils and elevated NET levels can be found in the adjacent tissue up to 60 days after the initial thermal injury in pigs and human, where the activated neutrophils produce large quantities of proteases and matrix metalloproteinases. This results in prolonged inflammation, increased tissue damage, and delayed wound healing, which in turn promotes formation of hypertrophic scars” (Page 2, 3rd paragraph).
Regarding claims 1 and 59, Farina et al. teach that trauma results from severe burn injury and “research seeking new mechanisms by which to attenuate inflammation after severe burn injury is needed” (Page 1, 1. Introduction) because” “Burn injury induces global changes to the entire immune system resulting in suppressed immune function and increased susceptibility to infection… Patients with severe burns are more likely to die from sepsis due to the massive release of inflammatory mediators from the burn wounds.” (Page 1, 2. Burns and Inflammation).
Regarding claims 1, 13, 59 and 69, Nam teaches that: “For the treatment of bums, it is quite important to heal the early burn wounds as fast as possible or to reduce the burned area. In the initial burn wound dressings, emphasis is placed on the initial treatment to prevent the transition to deep burns by control of infection and inflammation” [0004]. Nam teaches various causes of burns [0026], means of administration [0037]
Ascertainment of the difference between the prior art and the claims
(MPEP 2141.02) and Finding of prima facie obviousness
Rational and Motivation (MPEP 2142-2143)
The difference between the instant application and King et al. is that King et al. do not expressly teach that the inflammation is associated with burn injury resulting from exposure to a thermal, chemical, electrical, radiation source or combination thereof and administered as claimed in claim 19 that reduces the size of the burn as claimed to improve one or more symptoms of burn injury. This deficiency in King et al. is cured by the teachings of Sembrano, Nam, Farina et al. and Heuer et al.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to perform the method of King et al. on a subject with a burn injury, as suggested by Sembrano, Nam, Farina et al. and Heuer et al., and produce the instant invention. One of ordinary skill in the art would have been motivated to do this because Farina et al. and Heuer et al. establish that burn injury is a form of trauma and that inflammation is important in burn injuries where activated neutrophils can prolong inflammation, increase tissue damage and delay wound healing as taught by Heuer et al. Also, Farina et al. teach an express need in the art to attenuate inflammation in severe burn injury and Nam teaches the importance of controlling inflammation. Since the method of King et al. decreases or otherwise ameliorates the inflammatory response to physical trauma, and a burn is a form of physical trauma, then the ordinary artisan would have a reasonable expectation of success in performing the method of King et al. on a subject with a burn injury and improves one or more symptoms of burn injury as claimed and reduces the size of the burn area or by 5%, 10%, 20%, 30% or more compared to a control.
King et al. is silent on the cause of the burn injury but Nam and Sembrano teach that burns result from thermal, chemical, electrical and radiation. Thus, there is a reasonable expectation of success in treating a burn victim caused by any of those events.
Kin et al. appears silent on the administration regimen and all of the factors of instant claim 35. However, Sembrano not only teaches once daily or multiple times per day administration but also that those of skill in the art may readily determine the treatment regimen depending upon the concentration of active ingredient and upon the severity and size of the burn wound. Thus, the ordinary artisan in this art can optimize the treatment regimen in the patient’s best interest to heal the burn. Healing of the burn wound inherently means improving one or more symptoms of burn injury such as those found in claim 35. Especially when King et al. teach regeneration of epithelial cells [0032] and regeneration of damaged tissue (Claim 115; [00155]). The ordinary artisan would do so with a reasonable expectation of success.
The difference between the instant application and King et al. is that King et al. do not expressly teach wherein the negatively charged particles comprise iron, zinc, cadmium, gold or silver. However, King et al. teach: “negatively charged particles, such as polystyrene, PLGA, or diamond particles of a certain size and zeta potential, are administered to subjects, inflammatory immune responses are ameliorated…Negatively charged particles, therefore, may be useful in the treatment of any disease or condition characterized by an excessive inflammatory immune response”. [0053] The term “such as” means the components named are not limited but exemplary of negatively charged particles. King et al. also teach that in some embodiments, the particle is non-metallic [0064], which leaves the door open for metallic particles. Consequently, the ordinary artisan would have a reasonable expectation of success in employing any negatively charged particle, including metallic iron, zinc, cadmium, gold or silver in the method in the absence of evidence to the contrary.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the combined references, especially in the absence of evidence to the contrary.
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, 2, 6, 9, 13, 19, 21, 23, 25, 35, 36, 59, 60, 65, 69, 75, 77 and 80 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 20-22 and 26-31 of copending Application No. 17922484. The inventive entity of the copending application is different but the assignee, onCOUR Pharma, Inc., is the same. Although the claims at issue are not identical, they are not patentably distinct from each other because the copending teaches methods of treating ARDS or CSS in a subject with negatively charged PGA, PLA or PLGA having a negative zeta potential of -80 mV to -30 mV and a diameter of 0.3 to about 3 microns that are free from other therapeutically active agents (Claim 1) where the ARDS or CSS is a result of burn injury (Claim 3). The method improves the symptoms (Claims 27-30) and implicitly the symptoms from the burn injury. Intravenous administration is taught (Claim 31).
The copending does not expressly teach what the burn injury was a result from an exposure to a thermal source, chemical source, electrical source, radiation source, or any combination thereof . However, the ordinary artisan is aware that burn injury is at least caused by thermal means.
The copending does not expressly teach the treatment regimen. However, the treatment regiment such as once daily and means of administration such as orally, nasally, intramuscularly, ocularly, transdermally, or subcutaneously are obvious to the ordinary artisan to optimize the treatment for the desired outcome of healing the patient.
The copending does not expressly teach the reduction of burn area or the sequelae of claim 35. However, since the same particles with the same size and charge are taught by the copending application, then the same reduction and sequelae will be observed.
The copending does not teach administration of a second therapeutic agent. However, it is obvious to administer other therapeutics useful to treat burn injury for at least the additive effect in treatment.
Accordingly, the ordinary artisan would have recognized the obvious variation of the instantly claimed subject matter over the copending subject matter.
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 ERNST V ARNOLD whose telephone number is (571)272-8509. The examiner can normally be reached M-F 7-3:30.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Brian Y Kwon can be reached at 571-272-0581. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ERNST V ARNOLD/Primary Examiner, Art Unit 1613