Obviousness

A comprehensive obviousness analysis of US patent 12123035 under 35 U.S.C. § 103 requires access to two critical pieces of information that are not present in the provided patent text:

1. The specific claims of US12123035B2: Without the claims, it is impossible to define the metes and bounds of the invention and therefore determine what aspects would need to be rendered obvious by prior art.
2. The detailed technical disclosures of the identified prior art references: The provided text lists "Prior art keywords" (position corresponding, polypeptide, modified, agent, amino acid) and a "Prior art date" (2011-12-30) in the info box. Additionally, the "Definitions" section details the patent's lineage, mentioning U.S. Pat. No. 9,447,401 (issued Sep. 20, 2016), U.S. Pat. No. 10,865,400 (issued Dec. 15, 2020), U.S. Pat. No. 11,041,149 (issued Jun. 22, 2021), and U.S. Provisional Application Nos. 61/631,313 (filed Dec. 30, 2011) and 61/796,208 (filed Nov. 1, 2012). While these documents share the same title ("PH20 POLYPEPTIDE VARIANTS, FORMULATIONS AND USES THEREOF") and represent relevant art within the patent family, their specific technical disclosures are not provided in the current text.

Therefore, with high confidence, I cannot identify specific combinations of prior art references that would render the claims of US12123035B2 obvious, nor can I explain the motivation to combine them, as the essential elements for such an analysis (the claims and the detailed content of the prior art disclosures) are unavailable.

To properly perform the requested analysis, a person having ordinary skill in the art (PHOSITA) would need to:

• Review the claims of US12123035B2 to understand the specific scope of the invention, particularly concerning the "modified PH20 polypeptide variants, formulations and uses thereof" that exhibit "increased stability and/or increased activity."
• Examine the full text of the aforementioned patents and provisional applications, especially US 9,447,401, to ascertain what specific PH20 variants, modifications, formulations, or uses were disclosed and claimed prior to the effective filing date of any particular claim in US12123035B2.
• Consider any other relevant prior art that was publicly available before December 30, 2011, and that addresses "position corresponding," "polypeptide," "modified," "agent," or "amino acid" in the context of hyaluronidase variants.

General Background as Implicit Prior Art (without specific reference content):

The "Definitions" section of US12123035B2 does provide a general overview of the state of the art regarding hyaluronidases. It notes that "hyaluronidases have been used therapeutically (e.g., hyaluronidase sold under the trademarks Hydase® (bovine testicular hyaluronidase), Vitrase® (ovine hyaluronidase), and Wydase ⁇ (bovine hyaluronidase)), typically as dispersing and spreading agents in combination with other therapeutic agents." It further identifies a problem in the prior art, stating that "Many of these are ovine or bovine forms, which can be immunogenic for treatment of humans. Improved hyaluronan-degrading enzymes, such as hyaluronidases, and compositions thereof that can be used for treatment are needed."

If US12123035B2 were to claim, for example, a human PH20 variant with certain improved properties (e.g., increased stability in the presence of phenolic preservatives or at elevated temperatures), a PHOSITA would likely be motivated by the known therapeutic utility of hyaluronidases (as exemplified by bovine and ovine forms mentioned) and the recognized problem of their immunogenicity in humans. The general desire for "improved" enzymes would naturally lead a PHOSITA to explore modifications, such as amino acid replacements, to enhance properties like stability or activity in human PH20 polypeptides. However, without specific claims, it's impossible to determine if the particular modifications or resulting properties claimed in US12123035B2 would be rendered obvious by this general motivation or by specific teachings in the actual prior art documents of its lineage.