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 .
DETAILED ACTION
Status of the Claims
Claims 54 and 61-78 are pending and are examined on their merits.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Information Disclosure Statement
The Information Disclosure Statements filed on December 13th 2024 are in compliance with the provisions of 37 CFR 1.97 and have been considered in full. A signed copy of references cited from the IDS is included with this Office Action.
Nonstatutory 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).
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Claims 54 and 61-78 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12,338,205. Although the claims at issue are not identical, they are not patentably distinct from each other because:
The pharmaceutical composition of claim 54 incorporates the limitations of claims 2 and 17 of the reference patent.
The method of claim 61 incorporates the limitations of claims 2, 17, and 18 of the reference patent.
The method of claim 62 incorporates the limitations of claims 2, 17, and 19 of the reference patent.
The method of claim 63 incorporates the limitations of claims 2, 17, and 20 of the reference patent.
In addition to the limitations of claims 2 and 17 of the reference patent, the compositions of claims 64-68 incorporate the limitations of claims 3-7 of the reference patent, respectively.
Claims 69-78 only limit claims 62 and 63 by selecting a particular patient population from the list presented in claim 19 of the reference patent.
Claims 54 and 61-78 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 11,186,543 B2 (herein referred to as Lu) in view of Kumar (Kumar et al., Materials Chemistry and Physics, Volume 108, Issues 2–3, 2008, Pages 359-363).
The instant claims are directed towards pharmaceutical composition comprising a crystal form of 3-((L-valyl)amino)-1-propanesulfonic acid, a drug known for use in the treatment of Alzheimer’s disease. Said crystal form of 3-((L-valyl)amino)-1-propanesulfonic acid is characterized by x-ray diffraction peaks at 9.4°, 11.1°, 14.9°, 15.9°, 16.6°, 17.8°, 18.4°, 19.5°, 20.2°, 21.0°, 21.6°, 22.5°, 23.1°, 25.7°, 26.4°, 26.9°, 30.4°, 32.4°, and 34.5° and a differential scanning calorimetry curve with a melt temperature of about 301-312° C. Further claims limit characteristics of the crystal form, including:
The crystal has a space group of P43212, a unit cell volume of 2287.90(19) cubic Angstroms, and particular spatial dimensions.
The crystal form belongs to a tetragonal system.
The crystal size is 0.300 x 0.300 x 0.100 mm3.
Regarding these claims, Lu teaches a crystal form of 3-((L-valyl)amino)-3,3-dideuterium-1-propanesulfonic acid, the deuterated form of 3-((L-valyl)amino)-1-propanesulfonic acid. Lu’s compound, differing from the instant compound only in the addition of two neutrons, would have near-identical properties, both physical and chemical. This is evidenced by Lu’s crystal structure, which is characterized by:
X-ray diffraction peaks at 9.1°, 11.0°, 14.6°, 15.6°, 16.3°, 17.5°, 18.2°, 19.1°, 20.7°, 21.3°, 22.2°, 22.7°, 24.9°, 25.4°, 28.9°, 30.1°, 32.1°, and 34.2° (Lu, pg. 16, claims 1-3)
DSC melt temperature at 319° C (Lu, pg. 16, claim 8)
A space group of P43212, a unit cell volume of 2287.90(19) cubic Angstroms, and identical spatial dimensions to the unit cell of the instant crystal structure (Lu, pg. 16, claim 5)
A tetragonal system (Lu, pg. 16, claim 6)
The crystal size is 0.200 x 0.200 x 0.150 mm-3 (Lu, pg. 16, claim 7)
While Lu’s crystal form is deuterated and includes very minor differences from the instant crystal structure, one of ordinary skill in the art would have had a reasonable expectation of growing the non-deuterated form of 3-((L-valyl)amino)-1-propanesulfonic acid to have these properties, because deuterated crystals are known to have nearly identical crystal structures to the non-deuterated forms, with minor differences in thermal properties. For example, see Kumar, who compares the crystal structures of deuterated and non-deuterated L-threonine:
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(Kumar, pg. 360, Fig. 2)
All the peaks observed for both deuterated and normal l-threonine were at identical positions. The estimated lattice parameters a = 13.611 Å, b = 7.738 Å and c = 5.144 Å shows that there is no change in the crystal structure of l-threonine on deuteration. But the intensity of the diffracted peaks was found to be increase on deuterating the compound. The decrease in the full width half maximum (FWHM) values of all peaks and the increased intensities confirm that crystalline quality of the sample has been improved on deuteration.
[Kumar, pg. 360, Powder X-ray diffraction analysis]
Kumar demonstrates that the deuterated and non-deuterated forms of L-threonine, have identical crystal structures, with changes in intensity on the x-ray diffraction pattern, likely due to greater thermal stability of the deuterated form. This is further evidenced by Kumar’s differential scanning calorimetry data, which demonstrates a slight increase in thermal stability for the deuterated form of L-threonine in comparison to the non-deuterated form:
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(Kumar, pg. 361, Fig. 4)
Analogously, we can compare the x-ray diffraction patterns of the instant crystal structure (left) with Lu’s deuterated crystal structure (right):
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Each of the peaks appear in the same location, differing only in intensity and FWHM. Similarly, comparing the instant differential scanning calorimetry curve (left) with Lu’s curve (right):
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Lu’s curve, for the deuterated form of 3-((L-valyl)amino)-1-propanesulfonic acid, shows a melting temperature at 319° C, in contrast to 312° C for the non-deuterated form, corresponding to a minor increase in thermal stability for the deuterated form of the compound.
The properties of the instant crystal structure are therefore predictable from the deuterated crystal structure of Lu. Lu further teaches a pharmaceutical composition comprising the crystal form of the deuterated structure (Lu, pg. 17, claim 20). Claims 54 and 64-68 are thereby obvious.
Claims 61 and 62 are directed towards the treatment of an amyloid-ß related disease (Alzheimer’s disease, Parkinson’s disease, dementia) with the instant crystal form. Claim 63 recites the method of claim 61 wherein the subject is ApoE4 positive. Lu teaches treatment of the same conditions with the crystal form of the deuterated 3-((L-valyl)amino)-1-propanesulfonic acid (Lu, pg. 17, claims 21-22), including the case where the subject is Apo4E positive (Lu, pg. 17, claim 23). Claims 61-63 are therefore obvious.
Claims 69-78 limit the disease of claims 62 and 63 to Alzheimer’s disease, mild cognitive impairment, Heriditary Cerebral Hemorrhage with Amyloidosis of the Dutch-Type, cerebral amyloid angiopathy, degenerative dementia, dementia of mixed vascular and degenerative origin, and dementia associated with diffuse Lewy body type of Alzheimer’s disease, each of which is taught by claim 22 of the reference patent.
Claims 54 and 61-70 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,608,314 (herein referred to as Gu) in view of Kumar (Kumar et al., Materials Chemistry and Physics, Volume 108, Issues 2–3, 2008, Pages 359-363).
The instant claims are directed towards pharmaceutical composition comprising a crystal form of 3-((L-valyl)amino)-1-propanesulfonic acid, a drug known for use in the treatment of Alzheimer’s disease. Said crystal form of 3-((L-valyl)amino)-1-propanesulfonic acid is characterized by x-ray diffraction peaks at 9.4°, 11.1°, 14.9°, 15.9°, 16.6°, 17.8°, 18.4°, 19.5°, 20.2°, 21.0°, 21.6°, 22.5°, 23.1°, 25.7°, 26.4°, 26.9°, 30.4°, 32.4°, and 34.5° and a differential scanning calorimetry curve with a melt temperature of about 301-312° C. Further claims limit characteristics of the crystal form, including:
The crystal has a space group of P43212, a unit cell volume of 2287.90(19) cubic Angstroms, and particular spatial dimensions.
The crystal form belongs to a tetragonal system.
The crystal size is 0.300 x 0.300 x 0.100 mm3.
Regarding these claims, Gu teaches a crystal form of 3-((L-valyl)amino)-3,3-dideuterium-1-propanesulfonic acid, the deuterated form of 3-((L-valyl)amino)-1-propanesulfonic acid. Gu’s compound, differing from the instant compound only in the addition of two neutrons, would have near-identical properties, both physical and chemical. This is evidenced by Gu’s crystal structure, which is characterized by:
X-ray diffraction peaks at 9.1°, 11.0°, 14.6°, 15.6°, 16.3°, 17.5°, 18.2°, 19.1°, 20.7°, 21.3°, 22.2°, 22.7°, 24.9°, 25.4°, 28.9°, 30.1°, 32.1°, and 34.2° (Gu, pg. 16, claims 1-2)
DSC melt temperature at 319° C (Gu, pg. 16, claim 7)
A space group of P43212, a unit cell volume of 2288.57(19) cubic Angstroms, and near-identical spatial dimensions to the unit cell of the instant crystal structure (Gu, pg. 16, claim 4)
A tetragonal system (Gu, pg. 16, claim 4)
The crystal size is 0.200 x 0.200 x 0.150 mm-3 (Gu, pg. 16, claim 7)
While Gu’s crystal form is deuterated and includes very minor differences from the instant crystal structure, one of ordinary skill in the art would have had a reasonable expectation of growing the non-deuterated form of 3-((L-valyl)amino)-1-propanesulfonic acid to have these properties, because deuterated crystals are known to have nearly identical crystal structures to the non-deuterated forms, with minor differences in thermal properties. For example, see Kumar, who compares the crystal structures of deuterated and non-deuterated L-threonine:
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(Kumar, pg. 360, Fig. 2)
All the peaks observed for both deuterated and normal l-threonine were at identical positions. The estimated lattice parameters a = 13.611 Å, b = 7.738 Å and c = 5.144 Å shows that there is no change in the crystal structure of l-threonine on deuteration. But the intensity of the diffracted peaks was found to be increase on deuterating the compound. The decrease in the full width half maximum (FWHM) values of all peaks and the increased intensities confirm that crystalline quality of the sample has been improved on deuteration.
[Kumar, pg. 360, Powder X-ray diffraction analysis]
Kumar demonstrates that the deuterated and non-deuterated forms of L-threonine, have identical crystal structures, with changes in intensity on the x-ray diffraction pattern, likely due to greater thermal stability of the deuterated form. This is further evidenced by Kumar’s differential scanning calorimetry data, which demonstrates a slight increase in thermal stability for the deuterated form of L-threonine in comparison to the non-deuterated form:
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(Kumar, pg. 361, Fig. 4)
Analogously, we can compare the x-ray diffraction patterns of the instant crystal structure (left) with Gu’s deuterated crystal structure (right):
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media_image3.png
424
616
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Greyscale
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416
665
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Each of the peaks appear in the same location, differing only in intensity and FWHM. Similarly, comparing the instant differential scanning calorimetry curve (left) with Gu’s curve (right):
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504
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432
679
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Gu’s curve, for the deuterated form of 3-((L-valyl)amino)-1-propanesulfonic acid, shows a melting temperature at 319° C, in contrast to 312° C for the non-deuterated form, corresponding to a minor increase in thermal stability for the deuterated form of the compound.
The properties of the instant crystal structure are therefore predictable from the deuterated crystal structure of Gu. Gu additionally teaches a pharmaceutical composition comprising the crystal form of the deuterated structure (Lu, pg. 176, claim 1) and claims 54 and 64-68 are thereby obvious.
Claims 61 and 62 are directed towards the treatment of an amyloid-ß related disease (Alzheimer’s disease) with the instant crystal form. Claim 63 recites the method of claim 61 wherein the subject is ApoE4 positive. Claims 69 and 70 limit the disease of claims 62 and 63 to Alzheimer’s disease. Gu teaches treatment of Alzheimer’s disease with the crystal form of the deuterated 3-((L-valyl)amino)-1-propanesulfonic acid (Lu, pg. 16, claims 8), including the case where the subject is Apo4E positive (Gu, pg. 17, claim 9). Claims 61-63 and 69-70 are therefore obvious.
Conclusion
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/ANTHONY JOSEPH SEITZ/Examiner, Art Unit 1629
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