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 .
Response to Amendment
Applicant’s amendment filed on July 28, 2025 amending claims 1 and 17 has been entered. Claims 2-16 and 18-20 are canceled. Claims 1 and 17 are currently pending and presented for examination.
Response to Arguments
Applicant's arguments filed March 6, 2025 have been fully considered but they are not persuasive.
Applicant argues that claims 1 and 17 have been amended to recite wherein the Tacrolimus is administered in the amount of about 0.003 mg/kg to about 0.005 mg/kg and Applicant argues that Sun, in view of FDA, Solomon and Lyons, does not disclose, teach or suggest claims 1 and 17 since the rat dose of 0.05 mg/kg of tacrolimus taught in Sun would be about 0.008 mg/kg for a human which does not overlap with the human dose of tacrolimus as currently claimed of 0.003 mg/kg to about 0.005 mg/kg. In addition, Applicant argues that one skilled in the art would not be motivated to arrive at the claimed dosage of Tacrolimus based on the combined teachings of Sun, FDA, Solomon and/or Lyons.
These arguments are found not persuasive because Sun specifically teaches that in the case of injections, about 0.01-10 mg per day is given to adults at about 60 kg [0080]. The current claims recite an amount of about 0.003 mg/kg to about 0.005 mg/kg which for a 60 kg adult would be about 0.18 mg to about 0.3 mg which falls within the range of about 0.01-10 mg as taught in Sun. Furthermore, Sun specifically exemplifies the combination of the immunosuppressant tacrolimus (FK-506) at 0.05 mg/kg/day and the stem cell mobilizer AMD3100 at 1 mg/kg/day (ratio of 1/20) for subcutaneous administration to rats [0121]. Sun teaches that the data obtained from cell culture assays and animal studies may be used in formulating a range of dosages for use in humans [0076]. In the instant case, based on the animal data in Sun for rats, a skilled artisan practicing the invention in humans would convert an animal dose in mg/kg to a human equivalent dose by dividing the animal dose by 6.2 (for rats) or multiplying the animal dose by 0.16 (for rats) (see page 7 of Guidance for Industry). In the instant case, the rat dose of 0.05 mg/kg of tacrolimus taught in Sun would be about 0.008 mg/kg for a human; and a rat dose of 1 mg/kg of AMD3100 would be about 0.16 mg/kg for a human. Therefore, Sun specifically discloses combining at least one stem cell mobilizer (AMD3100) and at least one immunosuppressive agent (tacrolimus), wherein the immunosuppressive agent is an amount of about 0.008 mg/kg which is very close to the range of 0.003 mg/kg to about 0.005 mg/kg as claimed. A prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) (Court held as proper a rejection of a claim directed to an alloy of "having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium" as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties."). See also Warner-Jenkinson Co., Inc. v. Hilton Davis Chemical Co., 520 U.S. 17, 41 USPQ2d 1865 (1997) (under the doctrine of equivalents, a purification process using a pH of 5.0 could infringe a patented purification process requiring a pH of 6.0-9.0); In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%); In re Waite, 168 F.2d 104, 108 (CCPA 1948); In re Scherl, 156 F.2d 72, 74-75 (CCPA 1946) (prior art showed an angle in a groove of up to 90° and an applicant claimed an angle of no less than 120°); In re Swenson, 132 F.2d 1020, 1022 (CCPA 1942); In re Bergen, 120 F.2d 329, 332 (CCPA 1941); In re Becket, 88 F.2d 684 (CCPA 1937) ("Where the component elements of alloys are the same, and where they approach so closely the same range of quantities as is here the case, it seems that there ought to be some noticeable difference in the qualities of the respective alloys."); In re Dreyfus, 73 F.2d 931, 934 (CCPA 1934); In re Lilienfeld, 67 F.2d 920, 924 (CCPA 1933)(the prior art teaching an alkali cellulose containing minimal amounts of water, found by the Examiner to be in the 5-8% range, the claims sought to be patented were to an alkali cellulose with varying higher ranges of water (e.g., "not substantially less than 13%," "not substantially below 17%," and "between about 13[%] and 20%"); K-Swiss Inc. v. Glide N Lock GmbH, 567 Fed. App'x 906 (Fed. Cir. 2014)(reversing the Board's decision, in an appeal of an inter partes reexamination proceeding, that certain claims were not prima facie obvious due to non-overlapping ranges); Gentiluomo v. Brunswick Bowling and Billiards Corp., 36 Fed. App'x 433 (Fed. Cir. 2002)(non-precedential)(disagreeing with argument that overlapping ranges were required to find a claim prima facie obvious); In re Brandt, 886 F.3d 1171, 1177, 126 USPQ2d 1079, 1082 (Fed. Cir. 2018)(the court found a prima facie case of obviousness had been made in a predictable art wherein the claimed range of "less than 6 pounds per cubic feet" and the prior art range of "between 6 lbs./ft3 and 25 lbs./ft3" were so mathematically close that the difference between the claimed ranges was virtually negligible absent any showing of unexpected results or criticality.).
In addition, the secondary teachings of Lyons provide motivation to optimize the amount of tacrolimus for treating spinal cord injury since Lyons et al. specifically teaches that immunophilin ligands have a dramatic effect on nerve cells, and this effect is extraordinary in terms of potency, with as little as picomolar amounts of immunophilin ligand being neurotrophic (column 4 lines 3-7). Immunophilins are specific high-affinity receptors for immunosuppressant drugs that include cyclophilin and FKBP, which bind to cyclosporin A, and FK-506, respectively (column 4 lines 15-19). Thus the teachings of Lyons et al. suggest that the low dosages of FK-506 (tacrolimus) taught in Sun et al. and even lower dosages would be sufficient to treat spinal cord injury, and thus it would have been obvious to a person of ordinary skill in the art to vary and/or optimize the amount of tacrolimus such that optimal treatment of spinal cord injury is achieved and thus arrive at the instant invention. It has been held that it is within the skill in the art to select optimal parameters, such as amounts of ingredients, in a composition in order to achieve a beneficial effect. See In re Boesch, 205 USPQ 215 (CCPA 1980).
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) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); 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 re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art.").
Thus for reasons of record, and for the reasons detailed above, the previous rejection under 35 USC 103 is hereby maintained but modified in view of Applicant’s amendments to the claims. This action is FINAL.
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.
Claims 1 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over Sun et al. U.S. Publication No. 2013/0052231 A1 (Provided on IDS) in view of Guidance for Industry, July 2005, U.S. Depart. Of Health and Human Services, FDA, pages 1-30 (Provided on IDS); Lyons et al. U.S. Patent No. 6,080,753; and Solomon et al. WO 2015/031722 A1.
Claims 1 and 17 of the instant application claim a method of treating spinal cord injury or demyelination of neurons in a patient comprising administering to the patient a therapeutically effective amount of at least one stem cell mobilizer/CXCR4 antagonist such as AMD3100; at least one immunosuppressive agent/FK binding protein ligand such as tacrolimus (FK-506); wherein the amount of the immunosuppressive agent/FK binding protein ligand is about 0.003 mg/kg to about 0.005 mg/kg, wherein the AMD3100 and Tacrolimus are administered to the patient substantially simultaneously via subcutaneous injection, and wherein the AMD3100 and Tacrolimus are administered to the patient every other day.
Sun et al. teaches the combination of a stem cell mobilizer and an immunosuppressive agent [0005]. The stem cell mobilizer is preferably AMD3100 and the immunosuppressive agent is preferably tacrolimus administered in a low dose amount (0008]-[0010]). Sun et al. teaches a pharmaceutical composition comprising an effective amount of a stem cell mobilizer and an immunosuppressive agent [0069]. Sun et al. further teaches that the pharmaceutical composition further comprises a pharmaceutically acceptable carrier which is a diluent, adjuvant, excipient or vehicle with which the stem cell mobilizer and the immunosuppressive agent are administered [0070]. Such pharmaceutical carriers can be sterile liquids such as water and oils [0070]. Sun teaches that the pharmaceutical composition is preferably administered by subcutaneous injection [0072].
Sun teaches the pharmaceutical compositions may be administered about once every day, or about once every 2 days [0085]. Sun further teaches the pharmaceutical compositions of the present invention (e.g., a stem cell mobilizer and/or an immunosuppressive agent) can be administered simultaneously or sequentially by the same or different routes of administration [0090].
Sun et al. further teaches that the formulation is useful for the treatment of tissue injury ([0005], [0007], [0034], [0039], [0064], and [0069]). Sun specifically teaches that in the case of injections, about 0.01-10 mg per day is given to adults at about 60 kg [0080]. The current claims recite an amount of about 0.003 mg/kg to about 0.005 mg/kg which for a 60 kg adult would be about 0.18 mg to about 0.30 mg which falls within the range of about 0.01-10 mg as taught in Sun. Moreover, Sun et al. specifically teaches the combination of 0.1 mg/kg/day of tacrolimus (FK-506) and 1 mg/kg/day AMD3100 (ratio of 1/10) formulated for subcutaneous injection [0099]. Thus Sun et al. specifically teaches a ratio of 1/10 for the combination of tacrolimus (FK-506) and AMD3100 formulated for subcutaneous injection [0099]. In addition, Sun specifically teaches a ratio of 1/20 for the combination of tacrolimus (FK-506) (0.05 mg/kg) and AMD3100 (1 mg/kg) formulated for subcutaneous injection [0121] and [0126].
Sun specifically teaches the combination of the immunosuppressant tacrolimus (FK-506) at 0.05 mg/kg/day and the stem cell mobilizer AMD3100 at 1 mg/kg/day (ratio of 1/20) for subcutaneous administration to rats [0121]. Sun teaches that the data obtained from cell culture assays and animal studies may be used in formulating a range of dosages for use in humans [0076]. In the instant case, based on the animal data in Sun for rats, a skilled artisan practicing the invention in humans would convert an animal dose in mg/kg to a human equivalent dose by dividing the animal dose by 6.2 (for rats) or multiplying the animal dose by 0.16 (for rats) (see page 7 of Guidance for Industry). In the instant case, the rat dose of 0.05 mg/kg of tacrolimus taught in Sun would be about 0.008 mg/kg for a human; and a rat dose of 1 mg/kg of AMD3100 would be about 0.16 mg/kg for a human. Therefore, Sun specifically discloses combining at least one stem cell mobilizer (AMD3100) and at least one immunosuppressive agent (tacrolimus), wherein the immunosuppressive agent is in an amount of about 0.008 mg/kg.
Therefore, Sun specifically teaches a pharmaceutical composition comprising an effective amount of a stem cell mobilizer and an immunosuppressive agent and further comprising a pharmaceutically acceptable carrier, and furthermore specifically exemplifies an effective rat dosage of 0.05 mg/kg for the immunosuppressive agent (tacrolimus) which translates to an effective human dose of about 0.008 mg/kg.
Thus Sun et al. specifically teaches a pharmaceutical composition comprising at least one stem cell mobilizer that is AMD3100; at least one immunosuppressive agent that is tacrolimus; and a pharmaceutically acceptable carrier, wherein the composition is formulated for subcutaneous injection and wherein the ratio of tacrolimus to AMD100 is 1/10 or 1/20 and the amount of the immunosuppressive agent for humans is 0.008 mg/kg.
Sun does not teach the treatment of spinal cord injury or demyelination of neurons. Sun does not specifically exemplify the amount of the immunosuppressive agent/FK binding protein ligand between about 0.003 mg/kg to about 0.005 mg/kg.
However, Sun does specifically teach that the combination is for the treatment of tissue injury. Moreover, prior to the effective filing date of the instant application each of the components in the composition of Sun et al. were known individually to be useful in the treatment of spinal cord injury and/or demyelination of neurons.
Solomon et al. teaches the use of an inhibitor of CXCR4 for increasing remyelinization in motor neurons (abstract). Solomon et al. teaches that an example of an inhibitor of CXCR4 is AMD3100 which has been shown to rapidly mobilize hematopoietic stem and progenitor cells from the bone marrow into the blood of humans [0006]. Solomon et al. teaches that in the spinal cord of ALS mice, there was found extensive degeneration of gray matter oligodendrocytes resulting in progressive demyelination [0071]. Solomon et al. teaches that chronic treatment with AMD3100 induced significant remyelinization in motor neurons in the spinal cord demonstrating the ability of AMD3100 to induce remyelinization and treat spinal cord injury [0072].
Lyons et al. teaches that it is an object of the invention to provide a method of stimulating the growth of neuronal cells, a method of stimulating the regeneration of neurons after damage due to physical injury, and a method of stimulating the growth of neurons after damage due to disease (column 1 lines 45-55). These methods comprise administering to neuronal cells an immunophilin ligand in an amount sufficient to stimulate the growth of said neuronal cells, or administering to neuronal cells an immunophilin ligand and a neurotrophic factor, which provide methods of using pharmacologically acceptable substances for the regeneration of nerves after damage due to injury or disease (column 1 line 55-column 2 line 5). Lyons et al. teaches that immunophilin ligands have a dramatic effect on nerve cells, and this effect is extraordinary in terms of potency, with as little as picomolar amounts of immunophilin ligand being neurotrophic (column 4 lines 3-7). Immunophilins are specific high-affinity receptors for immunosuppressant drugs that include cyclophilin and FKBP, which bind to cyclosporin A, and FK-506, respectively (column 4 lines 15-19). In addition to these compounds, other immunophilin-binding drugs have been developed including rapamycin, FK-520, FK-523, 15-O-DeMe-FK-520,(4R)-[(E)-L-butenyl]-4,N-dimethyl-L-threonine (column 4 lines 19-22).
Claims 4-5 of Lyons et al. claim a method of stimulating growth of damaged neurons in the spinal cord of a patient suffering from Alzheimer's Disease, Parkinson's Disease, or physical damage to the spinal cord, comprising administering to said damaged neurons in the spinal cord a compound having an affinity for an FKBP in an amount sufficient to stimulate the growth of said damaged neurons, wherein the compound having an affinity for an FKBP is FK506. Claims 7-11 of Lyons et al. claim a method of stimulating growth of motor neurons in a patient suffering from Alzheimer's Disease, Parkinson's Disease, or physical damage to the spinal cord, comprising administering to said motor neurons a compound having an affinity for an FKBP in an amount sufficient to stimulate growth of said neurons, wherein the motor neurons are in a patient with amyotrophic lateral sclerosis and the compound having an affinity for an FKBP is FK506.
Accordingly, prior to the effective filing date of the instant application, it would have been obvious to a person of ordinary skill in the art to combine the teachings of Sun et al. which teaches a combination of at least one stem cell mobilizer that is AMD3100 and at least one immunosuppressive agent that is tacrolimus (FK-506) for the treatment of tissue injury, with the teachings of Solomon et al. which teaches that chronic treatment with AMD3100 induced significant remyelinization in motor neurons in the spinal cord demonstrating the ability of AMD3100 to induce remyelinization and treat spinal cord injury, and with the teachings of Lyons et al. which teaches a method of stimulating growth of damaged neurons in the spinal cord of a patient suffering from physical damage to the spinal cord, comprising administering to said damaged neurons in the spinal cord a compound having an affinity for an FKBP in an amount sufficient to stimulate the growth of said damaged neurons, wherein the compound having an affinity for an FKBP is FK506 (tacrolimus). Therefore, since both tacrolimus and AMD3100 were known in the art for the treatment of spinal cord injury, it would have been obvious to a person of ordinary skill in the art to use the combination of Sun comprising AMD3100 and tacrolimus for the treatment of spinal cord injury with a reasonable expectation of success. With respect to the immunosuppressive agent (tacrolimus) in the combination of Sun which translates to an effective human dose of about 0.008 mg/kg, Lyons et al. teaches that immunophilin ligands have a dramatic effect on nerve cells, and this effect is extraordinary in terms of potency, with as little as picomolar amounts of immunophilin ligand being neurotrophic (column 4 lines 3-7). Thus the amounts taught in Sun would be sufficient according to the teachings of Lyons et al. for stimulating the growth of damaged neurons and treating spinal cord injury. Therefore, the combination taught in Sun which comprises AMD3100 and tacrolimus would have been expected to treat spinal cord injury by inducing remyelinization of spinal cord neurons in view of the AMD3100 as taught by Solomon et al. and stimulating the growth of damaged neurons in view of the tacrolimus as taught by Lyons et al.
With respect to the immunosuppressive agent/FK binding protein ligand amounts as claimed between about 0.003 mg/kg to about 0.005 mg/kg, Sun specifically teaches that in the case of injections, about 0.01-10 mg per day is given to adults at about 60 kg [0080]. The current claims recite an amount of about 0.003 mg/kg to about 0.005 mg/kg which for a 60 kg adult would be about 0.18 mg to about 0.3 mg which falls within the range of about 0.01-10 mg as taught in Sun. Furthermore, Sun specifically exemplifies the combination of the immunosuppressant tacrolimus (FK-506) at 0.05 mg/kg/day and the stem cell mobilizer AMD3100 at 1 mg/kg/day (ratio of 1/20) for subcutaneous administration to rats [0121]. Sun teaches that the data obtained from cell culture assays and animal studies may be used in formulating a range of dosages for use in humans [0076]. In the instant case, based on the animal data in Sun for rats, a skilled artisan practicing the invention in humans would convert an animal dose in mg/kg to a human equivalent dose by dividing the animal dose by 6.2 (for rats) or multiplying the animal dose by 0.16 (for rats) (see page 7 of Guidance for Industry). In the instant case, the rat dose of 0.05 mg/kg of tacrolimus taught in Sun would be about 0.008 mg/kg for a human; and a rat dose of 1 mg/kg of AMD3100 would be about 0.16 mg/kg for a human. Therefore, Sun specifically discloses combining at least one stem cell mobilizer (AMD3100) and at least one immunosuppressive agent (tacrolimus), wherein the immunosuppressive agent is an amount of about 0.008 mg/kg which is very close to the range of 0.003 mg/kg to about 0.005 mg/kg as claimed. A prima facie case of obviousness exists where the claimed ranges or amounts do not overlap with the prior art but are merely close. Titanium Metals Corp. of America v. Banner, 778 F.2d 775, 783, 227 USPQ 773, 779 (Fed. Cir. 1985) (Court held as proper a rejection of a claim directed to an alloy of "having 0.8% nickel, 0.3% molybdenum, up to 0.1% iron, balance titanium" as obvious over a reference disclosing alloys of 0.75% nickel, 0.25% molybdenum, balance titanium and 0.94% nickel, 0.31% molybdenum, balance titanium. "The proportions are so close that prima facie one skilled in the art would have expected them to have the same properties."). See also Warner-Jenkinson Co., Inc. v. Hilton Davis Chemical Co., 520 U.S. 17, 41 USPQ2d 1865 (1997) (under the doctrine of equivalents, a purification process using a pH of 5.0 could infringe a patented purification process requiring a pH of 6.0-9.0); In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%); In re Waite, 168 F.2d 104, 108 (CCPA 1948); In re Scherl, 156 F.2d 72, 74-75 (CCPA 1946) (prior art showed an angle in a groove of up to 90° and an applicant claimed an angle of no less than 120°); In re Swenson, 132 F.2d 1020, 1022 (CCPA 1942); In re Bergen, 120 F.2d 329, 332 (CCPA 1941); In re Becket, 88 F.2d 684 (CCPA 1937) ("Where the component elements of alloys are the same, and where they approach so closely the same range of quantities as is here the case, it seems that there ought to be some noticeable difference in the qualities of the respective alloys."); In re Dreyfus, 73 F.2d 931, 934 (CCPA 1934); In re Lilienfeld, 67 F.2d 920, 924 (CCPA 1933)(the prior art teaching an alkali cellulose containing minimal amounts of water, found by the Examiner to be in the 5-8% range, the claims sought to be patented were to an alkali cellulose with varying higher ranges of water (e.g., "not substantially less than 13%," "not substantially below 17%," and "between about 13[%] and 20%"); K-Swiss Inc. v. Glide N Lock GmbH, 567 Fed. App'x 906 (Fed. Cir. 2014)(reversing the Board's decision, in an appeal of an inter partes reexamination proceeding, that certain claims were not prima facie obvious due to non-overlapping ranges); Gentiluomo v. Brunswick Bowling and Billiards Corp., 36 Fed. App'x 433 (Fed. Cir. 2002)(non-precedential)(disagreeing with argument that overlapping ranges were required to find a claim prima facie obvious); In re Brandt, 886 F.3d 1171, 1177, 126 USPQ2d 1079, 1082 (Fed. Cir. 2018)(the court found a prima facie case of obviousness had been made in a predictable art wherein the claimed range of "less than 6 pounds per cubic feet" and the prior art range of "between 6 lbs./ft3 and 25 lbs./ft3" were so mathematically close that the difference between the claimed ranges was virtually negligible absent any showing of unexpected results or criticality.).
In addition, the secondary teachings of Lyons provide motivation to optimize the amount of tacrolimus for treating spinal cord injury since Lyons et al. specifically teaches that immunophilin ligands have a dramatic effect on nerve cells, and this effect is extraordinary in terms of potency, with as little as picomolar amounts of immunophilin ligand being neurotrophic (column 4 lines 3-7). Immunophilins are specific high-affinity receptors for immunosuppressant drugs that include cyclophilin and FKBP, which bind to cyclosporin A, and FK-506, respectively (column 4 lines 15-19). Thus the teachings of Lyons et al. suggest that the low dosages of FK-506 (tacrolimus) taught in Sun et al. and even lower dosages would be sufficient to treat spinal cord injury, and thus it would have been obvious to a person of ordinary skill in the art to vary and/or optimize the amount of tacrolimus such that optimal treatment of spinal cord injury is achieved and thus arrive at the instant invention. It has been held that it is within the skill in the art to select optimal parameters, such as amounts of ingredients, in a composition in order to achieve a beneficial effect. See In re Boesch, 205 USPQ 215 (CCPA 1980).
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) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); 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 re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree "will not sustain a patent"); In re Williams, 36 F.2d 436, 438 (CCPA 1929) ("It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions."). See also KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying "the need for caution in granting a patent based on the combination of elements found in the prior art.").
Thus the cited claims of the instant application are rendered obvious in view of the cited prior art teachings.
Conclusion
Claims 1 and 17 are rejected. Claims 2-16 and 18-20 are canceled. No claims are allowed.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARA R. MCMILLIAN whose telephone number is (571)270-5236. The examiner can normally be reached Tuesday-Friday 12:00 PM-6:00 PM.
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, Adam C. Milligan can be reached on (571)270-7674. 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.
/KARA R. MCMILLIAN/Primary Examiner, Art Unit 1623
KRM