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 .
Claim Rejections - 35 USC § 112
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 1-10, 12-19 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
In this instance, the amount of experimentation is undue based on a consideration of at least the Wands factors as details below.
A) The breadth of the claims
Breadth of claim limitation “the one or more bioactive agent circulates through the lymphatic vasculature to one or more secondary lymphatic tissue” was not fully enabled by the disclosure.
B) The nature of the invention
The nature of the invention 2 and 50, 000 delivery structures, i.e. microneedle/needle to one or more sites of a skin of a patient having lymphatic vasculature.
C) The state of the prior art
The prior arts teach that injecting drugs at by using intradermal injection, intravenous, subcutaneous, intramuscular, or intradermal injections or oral delivery methods or a single administration depth in the dermis or to lymphatic system
D) The level of one of ordinary skill
A medical professional with sufficient skill and experience in working with delivering one or more agents to one or more lymphatic tissues of a subject. Delivering drugs by using intradermal injection to the lymphatic system, i.e. target the blood system, which at low rates, move out of the blood capillaries, into the interstitial tissues, and into the lymphatic system.
E) The level of predictability in the art
Generally understood to be predictable with regards to delivery to the lymphatic vasculature with parenteral administration methods, intravenous, subcutaneous, intramuscular, or intradermal injections or oral delivery methods. However, these parenteral administration methods above have been inconsistent and not reproducible. Injecting a drug at a single administration depth in the dermis can lead to patient-to-patient variability due to the drug being delivered in a location with reduced lymphatic capillaries or diffusion or movement of the drug deeper into the subcutaneous tissue.
F & G) The amount of direction provided by the inventor & the existence of working examples
Direction provided is for after administration and uptake, the one or more bioactive agents circulates through the lymphatic vasculature to one or more secondary lymphatic tissues comprising one or more lymph nodes, see claim 1 of the current application.
The inventor provides limited direction in the specification, claims, drawings, and abstract as originally filed. Although the specification provides Examples 1-4 of delivering one or more bioactive agents to the lymphatic vasculature. However, the disclosure lacks providing any support to get the result of the bioactive agent being circulates through the lymphatic vasculature or to one or more secondary lymphatic tissue.
Does the physician/clinician obtain any special technique such as rotating or vibrating the needle while injecting bioactive agents into the target area to get the result of the bioactive agent being circulated through the lymphatic vasculature?
In addition, it is unclear to Examiner that which tissue being considered as “one or more secondary lymphatic tissue comprising one or more lymph nodes”, as required in the claim 1. Can Applicant provide the drawing to show the primary lymphatic tissue, and the secondary lymphatic tissue?
H) The quantity of experimentation needs to make or use the invention based on the content of the disclosure.
As mentioned, Applicant provides Examples 1-4 of delivering one or more bioactive agents to the lymphatic vasculature. However,
one having ordinary skill in the art would not know how to get the claimed result of circulating the bioactive agents through the lymphatic vasculature... One having ordinary skill in the art would not be able to make or use the invention in its entire scope without undue experimentation because no explanation or guidance has been disclosed as getting a result of circulating the bioactive agents through the lymphatic vasculature...
Applicant may argue that one in the art would know how to make and use the invention; however, this would not be persuasive because the disclosure fails to include any special step or how to get the result of bioactive agent being circulated... without undue experimentation due to the broad nature of the claims.
As noted above Applicant has provided no way to determine the result as mentioned the above and therefore the amount of direction provided is insufficient to constitute an enabling disclosure.
Due to the failure of Applicant to adequately describe the invention, one would have to experiment unduly to reach the claimed result of the bioactive agents being circulated ... and thus the invention is not enabled.
112 6th Acknowledgement
With regard to Applicant’s “means for penetrating at least a most superficial layer of the epidermis” of claim 5, the language appears to be an attempt to invoke 35 USC 112, 6th paragraph interpretation of the claims. A claim limitation will be interpreted to invoke 35 U.S.C. 112, sixth paragraph, if it meets the following 3-prong analysis:
(A) the claim limitations must use the phrase “means for ” or “step for; ”
(B) the “means for ” or “step for ” must be modified by functional language;
and
(C) the phrase “means for ” or “step for ” must not be modified by sufficient structure, material or acts for achieving the specified function.
In the instant case, applicant appears to have met the limitations set forth in MPEP § 2181, and examiner has turned to the specification for clarification.
In the specification, applicant defines the “means for penetrating at least a most superficial layer of the epidermis” as a needle. Accordingly, the examiner is interpreting the “means for penetrating at least a most superficial layer of the epidermis” to encompass a needle and its equivalents. Equivalent structures may include those that perform the function specified in the claim, structures that are not excluded by any specific definition provided in the specification for an equivalent, or is a structural equivalent of the corresponding element disclosed in the specification. See MPEP 2183.
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.
Claim 19 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.
The limitations in claim 19 is identical to the limitations in claim 1. Therefore, the claim 19 should be cancelled.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-7, 9-10, 12-19 are rejected under 35 U.S.C. 103 as being unpatentable over Allen et al. (US 6,334,856)
Regarding claims 1 & 19, Allen discloses a method of treating a subject with a disease comprising one or more sites of lymphadenitis (col. 3, line 66) by administering one or more bioactive agents to the one or more sites of lymphadenitis comprising:
(a) applying one or more delivery devices having between 2 and 50,000 delivery structures (e.g. multiple microneedle arrays, Fig. 1A. Therefore, the delivery device or the needle having more than 2 or between 2 to 50,000 delivery structures to one or more sites of a skin of a subject having lymphatic vasculature, (lymphatic vessels, col. 3, line 66), wherein the delivery device contacts one or more layers of epidermis with one or more reversible permeability enhancers comprising a chemical, physical or electrical permeability enhancer, col 7,lines 31-36, that will bring a result of inducing a reversible increase in the permeability of one or more barrier cells of the epidermis to at least one or more bioactive agents;
(b) administering a total liquid dosage (total amount of injection) in between 2 and 50,000 sub-doses of the one or more bioactive agents at a controlled administration flow rate through the delivery device, col. 16, lines 46-66.
Note: each of the microneedle arrays holds at least one small sub-doses (compare with a total liquid dosage = total amount of each sub-doses contained in the microneedle arrays) for inserting into target sites.
wherein each sub-dose (holding by each of the microneedles) of the one or more bioactive agents is independently administered (each of the microneedle arrays holds independently at least one sub-dose of the bioactive agent), in an administering step, to a plurality of independent depths ranging from about less than 100 µm, more preferably about 30 µm, (col. 9, lines 2-4, which is in a required range of 1 to about 500 µm) beyond a most superficial surface layer of the epidermis of the subject prior to any subsequent diffusion or movement of the one or more bioactive agents within the epidermis, see Fig. 1A;
With regarding the limitations “wherein following the administering, the one or more bioactive agents moves or diffuses deeper through the epidermis through a basal layer of the epidermis and into at least a portion of underlying viable dermis to achieve an uptake of a portion of the one or more bioactive agents by one or more susceptible lymphatic capillary plexus to achieve a greater delivery of the one or more bioactive agents to the lymphatic vasculature compared to intravenous, intradermal, or subcutaneous delivery of the identical one or more bioactive agents” is a functional limitation or a result of administering 2-50,000 sub-doses of the bioactive agent(s) with an insertion depth ranging from 1-500 µm beyond a most superficial surface layer of the epidermis of the subject. Having said the above, since Allen discloses a method of providing 2 to 50,000 sub-doses of the bioactive agents with the insertion into the epidermis (a plurality of independent depths ranging from 1 to less 100 µm, more preferably about 30 µm). Therefore, following the administering step, the result of the one or more bioactive agents in Allen moves or diffuses deeper through the epidermis through a basal layer of the epidermis and into at least a portion of underlying viable dermis to achieve an uptake of a portion of the one or more bioactive agents by one or more susceptible lymphatic capillary plexus to achieve a greater delivery of the one or more bioactive agents to the lymphatic vasculature (e.g. the transport of material, i.e. bioactive agents into or across the lymphatic vessels, col. 3,lines 60-66) compared to intravenous, intradermal, or subcutaneous delivery of the identical one or more bioactive agents
With regarding the limitations “wherein after administration and uptake, the one or more bioactive agents circulates through the lymphatic vasculature to one or more secondary lymphatic tissues comprising one or more lymph nodes, thereby -65-38108-491administering the one or more bioactive agents to the one or more sites of lymphadenitis”, it is a result of delivering the one or more bioactive agent by using the delivery device (having between 2 and 50,000 delivery/needle structures such as microneedle array) with insertion depth from 1-500 µm, i.e. within the epidermis layer. In this case, Allen discloses a same concept of using microneedle arrays (having between 2 to 50,000 delivery/needle structures) for delivering one or more bioactive agent in combine with one or more permeability enhancers into the epidermis tissue and therefore, the bioactive agents is moving and diffusing deeper through the epidermis through a basal layer of the epidermis and into at least a portion of underlying viable dermis and through to lymphatic vasculature (i.e. the bioactive agent into or across the lymphatic vessels, col. 3, lines 60-66) to one more secondary lymphatic tissue comprising one or more lymph nodes, thereby administering the one or more bioactive agents to the one or more sites of lymphadenitis.
In addition, Applicant admits in paras [0101-1003], or it is well-known (or inherently) that lymphatic vessels are vessels that form pathways for discharging tissue fluid separate from circulation system. Therefore, when the bioactive agent moves into or through the lymphatic vascular to one or more secondary lymphatic tissue in circulation flowing.
Regarding claim 2, Allen discloses that wherein an average of the plurality of independent depths exhibits a combined average sub-dose delivery depth within the epidermis, e.g., a plurality of independent depths ranging from 1 to less 100 µm, more preferably about 30 µm, col. 9, lines 2-4 and also see Fig. 1A, which is beyond a most superficial surface layer of the epidermis.
Regarding claim 3, similar to the analysis as mentioned in the claim 2 above. Allen also discloses that wherein the plurality of independent depths has a combined average depth of administration within the epidermis, wherein each independently administered sub-dose is at a depth within the epidermis that is deeper, shallower, or the same.
Regarding claim 4, as best as understood, Allen also discloses that wherein a frequency of each of the independent sub-dose administration depths within the viable epidermal layer and/or a non-viable epidermal layer exhibits a Gaussian distribution (normal distribution) of depths.
Regarding claim 5, Allen discloses that wherein the delivery device comprises an array (multiple microneedle arrays) comprising between 2 and 50,000 of the delivery structures in fluid communication with the one or more bioactive agents in a liquid carrier vehicle (a reservoir for holding the bioactive agent within the upper portion 11, co. 15, lines 64-65; or a channel/lumen/bore formed in a hollow of the microneedle for delivering drugs, or micropump, col. 5, lines 8-26, col. 7, lines 7-15);
wherein the delivery device comprises a means for controlling the administration flow rate including at least one component selected from the group consisting of a pump (micropumps), a fluid delivery rate controller, or any combination thereof, see col. 7,lines 1-21;
wherein the delivery structures comprise a means (i.e. microneedle arrays device or needle) for penetrating at least a most superficial layer of the epidermis, see Fig. 1A; and
wherein the one or more bioactive agents in a liquid carrier vehicle is delivered by the delivery structures to the plurality of depths within the viable epidermis of a subject, thereby administering between 2 and 50,000 sub-doses of the one or more bioactive agents.
Regarding claim 6, Allen discloses that wherein the delivery structures comprise a standard or nonstandard geometric shape, col. 5, lines 27-57.
Regarding claim 7, Allen discloses that wherein the delivery structures comprise needles.
Regarding claim 8, this claim is being rejected using same analysis as noted in the claim 1 above. However, Allen does not disclose the limitation that the flow rate about 0.01-100 µl/hr per each of the delivery structures at a total combined controlled administration flow rate about 0.02-50,000 µl/hr/cm2 based on a total surface area of the one or more delivery devices that is in contact with the skin of the subject.
It would have been obvious to one having ordinary skill in the art at the time of the invention was made to provide a flow rate the flow rate about 0.01-100 µl/hr per each of the delivery structures at a total combined controlled administration flow rate about 0.02-50,000 µl/hr/cm2, since it has been held that discovering an optimum value of a result effective variable involves only routine skill in the art. For example: it depends on type of skin of children, male, female ... it also depends on age, and depends on each treatment of the disease. In addition, the flow rate based on the total surface area that depends on the size of tumors, the treatment of each condition of a patient.
Regarding claim 9, Allen discloses the claimed invention, as discussed in the claim 1 above. Allen further discloses that wherein the one or more bioactive agents is delivered to a tissue volume of the epidermis encompassing the one or more bioactive agents prior to any subsequent diffusion or movement of the one re more bioactive agent within the epidermis at variable volume rates, col. 16, lines 20-col. 17, line 12. However, Allen does not disclose the volume of the delivered bioactive agent of about 0.7 mm3 to about 2,500 mm3. It would have been obvious to one having ordinary skill in the art at the time of the invention was made to obtain the values above, since it has been held that discovering an optimum value of a result effective variable involves only routine skill in the art. In addition, it depends on the treatment of each patient such as number of doses, or pressure/force being injected into the target epidermis.
Regarding claim 10, Allen discloses the claimed invention, as discussed in the claim 110. The method according to claim 1. Allen discloses that the one or more bioactive agents is continuously administered to a subject for a time period of about 0.1 hours to about 96 hours (e.g. the device is affixed to the skin or other tissue to deliver drugs continuously... ranging from a few seconds to several hours to days, col 16, lines 60-63.
Regarding claim 12, Allen discloses that the physical permeability enhancer comprises a nanostructured (nanometers, col. 9, lines 41-42), or nanotopography surface (e.g. porous structure, col. 5, lines 7-13, col. 11, lines 15-46.
Regarding claim 13, Allen discloses the claimed invention, as discussed in the claim 1 above except for the limitation that wherein administration of one or more bioactive agents achieves a dermal interstitial fluid pressure in the underlying dermis beneath a site of administration of about 1 mmHg to about 15 mmHg. It would have been obvious to one having ordinary skill in the art at the time of the invention was made to obtain the values above, since it has been held that discovering these values (e.g. 1 mmHg to about 15 mmHg) of a result effective variable involves only routine skill in the art. For example, the dermal interstitial fluid pressure value depends on the skin characteristic of each patient (children, adult, male, female or old patient) and depends on using pressure/force being injected into the target epidermis.
Regarding claim 14, Allen discloses the claimed invention, as discussed in the claim 1 above except for the limitation that wherein a relative concentration of one or more bioactive agents within the one or more lymphatic tissues is about 1.25 fold to about 50 fold more than intravenous, intradermal, or subcutaneous delivery of the identical one or more bioactive agents. It would have been obvious to one having ordinary skill in the art at the time of the invention was made to obtain the values above, since it has been held that discovering these values (e.g. 1.25 fold to about 50 fold) of a result effective variable involves only routine skill in the art.
Regarding claim 15, as best as understood, Allen discloses the claimed invention, as discussed in the claim 1 above. A person skilled in the art would recognize that wherein a blood serum absorption rate of the one or more bioactive agents is equivalent to intradermal delivery and subcutaneous delivery of the identical one or more bioactive agents.
Regarding claims 16-17, Allen discloses the claimed invention, as discussed in the claim 1 above except for the limitations that wherein a ratio of an initial dose of one or more bioactive agents localized per gram of lymph node tissue to a whole blood tissue is from about 5:1 to about 15:1 after about 36 hours.
It would have been obvious to one having ordinary skill in the art at the time of the invention was made to obtain the values above, since it has been held that discovering these ratio values in claims 16-17 of a result effective variable involves only routine skill in the art. For example: it depends on each treatment of each patient that determined by a physician.
Regarding claim 18, Allen discloses the claimed invention, as discussed in the claim 1 above 18. The method according to claim 1, wherein the bioactive agent is useful for treating, retarding the progression of, delaying the onset of, or reducing the symptoms of an auto immune disease comprising at least one or more areas of lymphadenitis, col. 3, line 60-col. 4, line 4.
Claims 1-10, 13-19 are rejected under 35 U.S.C. 103 as being unpatentable over Pettis et al. (US 2005/0180952).
Regarding claims 1 & 19, Pettis discloses a method of treating a subject with a disease comprising one or more sites of lymphadenitis by administering one or more bioactive agents to the one or more sites of lymphadenitis comprising:
(a) applying one or more delivery devices having between 2 and 50,000 delivery structures (e.g. multiple microneedle arrays, para [0080], therefore, the delivery device or the needle having more than 2 or in the requirement ranges between 2 to 50,000 delivery structures) to one or more sites of a skin of a subject having lymphatic vasculature, (see abstract, para [0002]), wherein the delivery device contacts one or more layers of epidermis (e.g. the formulations are delivered at a targeted depth just under the stratum corneum and encompassing the epidermis and upper dermis, para [0082]) with one or more reversible permeability enhancers comprising: electrical permeability enhancer (e.g. the microneedle array being used to delivery bioactive agents by electric field, such as iontophoresis, para [0078]). Pettis also states in the Back Ground of the Invention that it is well-known in the art to delivery drug with rely upon a chemical permeability enhancer (chemical mediators, para [0003]) or physical permeability enhancer (hydrophobic adsorption, para [0004]) or electrical permeability enhancer (e.g. the microneedle array being used to delivery bioactive agents by electric field, such as iontophoresis, paras [0003], sonophoresis, para [0003], electroporation, para [0003]) that induces a reversible increase in the permeability of one or more barrier cells of the epidermis to at least one or more bioactive agents (para [0002]);
Note: the limitation “... that induces a reversible increase in the permeability of one or more barrier cells of the epidermis to at least one or more bioactive agents” is a result of using delivery device (such as microneedle arrays or needle device) being inserted into the one or more layer of epidermis with combine of using one or more reversible permeability enhancers. Therefore, Pettis discloses all the claimed subject matter as discussed in the step a) above.
(b) administering a total liquid dosage (total amount of injection) in at least 2 sub-doses (in between required ranges of 2 and 50,000 sub-doses) of the one or more bioactive agents at a controlled administration flow rate through the delivery device, para [0019-0021, 0090-0091]. For example: each of the microneedle arrays holds at least one small sub-doses (compare with a total liquid dosage = total amount of each sub-doses contained in the microneedle arrays) for inserting into one or more sites of lymphadenitis (lympathic vasculature). The microneedle array is used to increase the rate of delivery or the amount of agent delivered in a given period of time instead of using one needle injection.
wherein each sub-dose of the one or more bioactive agents is independently administered (each of the microneedle arrays holds independently at least one sub-dose of the bioactive agent), in an administering step, to a plurality of independent depths ranging from about 0.025- 2.5mm = 25-2500 µm, para [0082] (which is in a required range of 1 to about 500 µm) to bring the result of the independent depths being beyond a most superficial surface layer of the epidermis of the subject (e.g. the formulations are delivered at a targeted depth just under the stratum corneum and compassing the epidermis and upper dermis, para [0082]) prior to any subsequent diffusion or movement of the one or more bioactive agents within the epidermis;
With regarding the limitations “wherein following the administering, the one or more bioactive agents moves or diffuses deeper through the epidermis through a basal layer of the epidermis and into at least a portion of underlying viable dermis to achieve an uptake of a portion of the one or more bioactive agents by one or more susceptible lymphatic capillary plexus to achieve a greater delivery of the one or more bioactive agents to the lymphatic vasculature compared to intravenous, intradermal (into the dermis layer), or subcutaneous delivery of the identical one or more bioactive agents” is a functional limitation or a result of administering 2-50,000 sub-doses of the bioactive agent(s) with an insertion depth ranging from 0.025- 2.5mm = 25-2500 µm, para [0082] (which is in a required range of 1 to about 500 µm) beyond a most superficial surface layer of the epidermis of the subject. Having said the above, Pettis discloses the administering 2-50,000 sub-doses of the bioactive agent(s) with an insertion depth ranging from 0.025- 2.5 mm = 25-2500 µm beyond a most superficial surface layer of the epidermis of the subject, also see claims 1. Therefore, Pettis clearly discloses the limitations as required the above such as: wherein following the administering, the one or more bioactive agents moves or diffuses deeper through the epidermis through a basal layer of the epidermis and into at least a portion of underlying viable dermis, para [0021], to achieve an uptake of a portion of the one or more bioactive agents by one or more susceptible lymphatic capillary plexus to achieve a greater delivery of the one or more bioactive agents to the lymphatic vasculature compared to intravenous, or subcutaneous delivery of the identical one or more bioactive agents”.
With regarding the limitations “wherein after administration and uptake, the one or more bioactive agents circulates through the lymphatic vasculature to one or more secondary lymphatic tissues comprising one or more lymph nodes, thereby -65-38108-491administering the one or more bioactive agents to the one or more sites of lymphadenitis”, it is a result of delivering the one or more bioactive agent by using the delivery device (having between 2 and 50,000 delivery/needle structures such as microneedle array). In this case, Pettis discloses a same concept of using microneedle arrays (having between 2 to 50,000 delivery/needle structures) for delivering one or more bioactive agent in combine with one or more permeability enhancers (e.g. iontophoresis) into the epidermis tissue (as discussed above) and therefore, the bioactive agents circulates (the distribution with high bioavailability to the lymphatic tissue local to the administration site, followed by a more wide spread lymphatic delivery into the general circulation, para [0015]) and diffusing deeper through the epidermis through a basal layer of the epidermis and into at least a portion of underlying viable dermis and through to one or more secondary lymphatic tissues comprising one or more lymph nodes, para [0017]) and thereby -65-38108-491administering the one or more bioactive agents to the one or more sites of lymphadenitis.
Regarding claim 2, Pettis discloses that wherein an average of the plurality of independent depths exhibits a combined average sub-dose delivery depth within the epidermis of about 0.025 to 2.5 mm (250-2500 µm, para [0082], which is within the required ranges of 70-175 µm) beyond a most superficial surface layer of the epidermis.
Regarding claim 3, similar to the analysis as mentioned in the claim 2 above. Pettis also discloses that wherein the plurality of independent depths has a combined average depth of administration within the epidermis, wherein each independently administered sub-dose is at a depth within the epidermis that is deeper, shallower, or the same. For example: each patient has different thickness value of the epidermis tissue, and depend on a target treatment area in deep or shallow area.
Regarding claim 4, as best as understood, Pettis also discloses that wherein a frequency of each of the independent sub-dose administration depths within the viable epidermal layer and/or a non-viable epidermal layer exhibits a Gaussian distribution (normal distribution) of depths.
Regarding claim 5, Pettis discloses that wherein the delivery device comprises an array (multiple microneedle arrays, para [0080], therefore the microneedle arrays is more than 2), comprising between 2 and 50,000 of the delivery structures in fluid communication with the one or more bioactive agents in a liquid carrier vehicle (a reservoir for holding bioactive agent or a holder, paras [0089-0090, 0098]);
wherein the delivery device comprises a means for controlling the administration flow rate including at least one component selected from the group consisting of a pump, a fluid delivery rate controller, a syringe, a pen, an elastomer membrane, or any combination thereof, see paras [0090, 0098])
wherein the delivery structures comprise a means (i.e. microneedle arrays device or needle) for penetrating at least a most superficial layer of the epidermis; and wherein the one or more bioactive agents in a liquid carrier vehicle is delivered by the delivery structures to the plurality of depths within the viable epidermis of a subject, thereby administering between 2 and 50,000 sub-doses of the one or more bioactive agents.
Regarding claim 6, Pettis discloses that wherein the delivery structures comprise a standard or nonstandard geometric shape, para [0080].
Regarding claim 7, Pettis discloses that wherein the delivery structures comprise microneedles or needles.
Regarding claim 8, this claim is being rejected using same analysis as noted in the claim 1 above. However, Pettis does not disclose the limitation that the flow rate about 0.01-100 µl/hr per each of the delivery structures at a total combined controlled administration flow rate about 0.02-50,000 µl/hr/cm2 based on a total surface area of the one or more delivery devices that is in contact with the skin of the subject.
It would have been obvious to one having ordinary skill in the art at the time of the invention was made to provide a flow rate the flow rate about 0.01-100 µl/hr per each of the delivery structures at a total combined controlled administration flow rate about 0.02-50,000 µl/hr/cm2, since it has been held that discovering an optimum value of a result effective variable involves only routine skill in the art. For example: it depends on type of skin of children, male, female ... it also depends on age, and depends on each treatment of the disease. In addition, the flow rate based on the total surface area that depends on the size of tumors, the treatment of each condition of a patient.
Regarding claim 9, Pettis discloses the claimed invention, as discussed in the claim 1 above except for the limitation that the one or more bioactive agents is delivered to a tissue volume of the epidermis encompassing the one or more bioactive agents prior to any subsequent diffusion or movement of the one or more bioactive agents within the epidermis except for the value of diffusion or movement of the one or more bioactive agents within the epidermis 0.7 mm3 to about 2,500 mm3. It would have been obvious to one having ordinary skill in the art at the time of the invention was made to obtain the values above, since it has been held that discovering an optimum value of a result effective variable involves only routine skill in the art. In addition, it depends on the treatment of each patient such as number of doses, or pressure/force being injected into the target epidermis.
Regarding claim 10, Pettis discloses the claimed invention, as discussed in the claims 1 & 10. It is well-known in the medical art that for treating cancer or depending on the condition of the patient, the doctor must subscribe a treatment at least continuously administered in certain time. The continuous amount of time period of about 0.1 hours to about 96 hours that involves only routine skill in the art. For example: the injection in 5-10 seconds, para [0079]; or an example to delivery at lung tissue at 3hrs, para [0230]
Regarding claim 13, Pettis discloses the claimed invention, as discussed in the claim 1 above except for the limitation that wherein administration of one or more bioactive agents achieves a dermal interstitial fluid pressure in the underlying dermis beneath a site of administration of about 1 mmHg to about 15 mmHg. It would have been obvious to one having ordinary skill in the art at the time of the invention was made to obtain the values above, since it has been held that discovering these values (e.g. 1 mmHg to about 15 mmHg) of a result effective variable involves only routine skill in the art. For example, the dermal interstitial fluid pressure value depends on the skin characteristic of each patient (children, adult, male, female or old patient) and depends on using pressure/force being injected into the target epidermis.
Regarding claim 14, Pettis discloses the claimed invention, as discussed in the claim 1 above except for the limitation that wherein a relative concentration of one or more bioactive agents within the one or more lymphatic tissues is about 1.25 fold to about 50 fold more than intravenous, intradermal, or subcutaneous delivery of the identical one or more bioactive agents. It would have been obvious to one having ordinary skill in the art at the time of the invention was made to obtain the values above, since it has been held that discovering these values (e.g. 1.25 fold to about 50 fold) of a result effective variable involves only routine skill in the art.
Regarding claim 15, as best as understood, Pettis discloses the claimed invention, as discussed in the claim 1 above. A person skilled in the art would recognize that wherein a blood serum absorption rate of the one or more bioactive agents is equivalent to intradermal delivery and subcutaneous delivery of the identical one or more bioactive agents.
Regarding claims 16-17, Pettis discloses the claimed invention, as discussed in the claim 1 above except for the limitations that wherein a blood serum absorption rate of the one or more bioactive agents is equivalent to intradermal delivery and subcutaneous delivery of the identical one or more bioactive agents; wherein a ratio of an initial dose of one or more bioactive agents localized per gram of lymph node tissue to a whole blood tissue is from about 5:1 to about 15:1 after about 36 hours.
It would have been obvious to one having ordinary skill in the art at the time of the invention was made to obtain the values above, since it has been held that discovering these ratio values in claims 16-17 of a result effective variable involves only routine skill in the art. For example: it depends on each treatment of each patient that determined by a physician.
Regarding claim 18, Pettis discloses the claimed invention, as discussed in the claim 1 above, wherein the bioactive agent is useful for treating, retarding the progression of, delaying the onset of, prophylaxis of, amelioration of, or reducing the symptoms of an auto immune disease comprising at least one or more areas of lymphadenitis, see abstract, paras [0014-0017].
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Pettis et al. (US 2005/0180952) in view of Ross (US 2013/0144257).
Pettis discloses the invention substantially as claimed invention except for the limitation the physical permeability enhancers (of the microneedle arrays) comprises a nanostructured or nanotopography surface.
Ross discloses a microneedle transdermal device 10 comprising: a microneedle arrays 12/22 with permeability enhancer (e.g. the microneedle array being used by electric field, such as iontophoresis for delivering bioactive agents); wherein the physical permeability enhancers comprise a nanostructured or nanotopography surface 26, see abstract, Fig. 3.
It would have been obvious at the time the invention was made to a person having ordinary skill in the art to modify the device of Pettis with providing a physical permeability enhancer with a nanostructured or nanotopography surface, as taught by Ross, in order to allow the surface of the microneedle being interacted with the cells of the dermal barrier and improve efficiency of delivery and uptake of the bioactive agents, para [0071] in Ross.
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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-10 & 12-19 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 10,737,082 and claims 1-14 of U.S. Patent No. 10,806,913. Although the conflicting claims are not identical, they are not patentably distinct from each other because they are not structurally distinguishable from the claims in the patents.
Examiner Notes
Examiner cites particular columns and line numbers in the references as applied to the claims above for the convenience of the applicant. Although the specified citations are representative of the teachings in the art and are applied to the specific limitations within the individual claim, other passages and figures may apply as well. It is respectfully requested that, in preparing responses, the applicant fully consider the references in entirety as potentially teaching all or part of the claimed invention, as well as the context of the passage as taught by the prior art or disclosed by the examiner.
Conclusion
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/Quynh-Nhu H. Vu/
Quynh-Nhu H Vu
Primary Examiner, Art Unit 3783
Prosecution Insights