Obviousness

Based on my analysis of US patent 10,792,416 ('416 patent) and the principles of patent law under 35 U.S.C. § 103, the claims of this patent would likely be found obvious in light of a combination of prior art references that existed before the priority date of May 30, 2017.

A person having ordinary skill in the art (POSITA) in the field of apheresis technology would be familiar with automated blood component separation systems, the need to control collection volumes based on donor parameters for safety and regulatory compliance, the fact that collected plasma is mixed with anticoagulant, and the importance of managing a donor's fluid balance.

The following analysis outlines potential combinations of prior art that would render the independent claims of the '416 patent obvious.

Obviousness of Claim 1 (Method) and Claim 11 (System)

Claim 1 describes a method of stopping plasma collection based on a calculated pure plasma volume, where the target is based on donor weight. Claim 11 describes the system with a controller that automates this method. Both are addressed by the same core logic.

Proposed Combination of Prior Art: A primary reference teaching a personalized apheresis procedure (a "base system") combined with a secondary reference teaching the calculation of plasma concentration in an anticoagulated product.

• Base System Reference (e.g., US 7,655,148 to Felt): The art is replete with apheresis systems that personalize a collection procedure based on donor data. For example, systems developed by companies like Fresenius Kabi, Terumo BCT, or Haemonetics itself taught inputting donor parameters like weight and hematocrit to determine a target collection volume. These systems automate the process of drawing blood, separating components, and stopping collection when a scale indicates the target weight/volume of the final product (plasma plus anticoagulant) is reached. This prior art establishes the foundational steps of Claim 1 (a-f) and the basic hardware of Claim 11 (a-d).

• Secondary Calculation Reference (e.g., US 6,582,349 to Steele): The art also recognized that the collected product was not pure plasma. It was well understood that the concentration of anticoagulant in the final product varied depending on the donor's hematocrit and the ratio of anticoagulant mixed with whole blood. References like Steele teach the principle and provide the mathematical basis for determining the actual amount of plasma in a collected volume of anticoagulated plasma. This directly teaches the concepts behind calculating the percentage of anticoagulant (Claim 1, element g) and the resulting pure plasma volume (Claim 1, element h).

Motivation to Combine and Rationale for Obviousness:

A POSITA working with a base system would have been motivated to incorporate the teachings of a reference like Steele for several reasons:

1. Regulatory Compliance: The '416 patent's own background section notes that the FDA sets limits on the volume of plasma that may be collected. A system that stops based on the total volume of an anticoagulated mixture does not precisely measure compliance with this limit. For two donors of the same weight, one with a low hematocrit will donate more actual plasma than a donor with a high hematocrit before the machine stops. To ensure the collection limit for pure plasma is not exceeded and to standardize the procedure, a POSITA would have found it obvious to use the known calculations (as in Steele) to control the endpoint of the collection.

2. Product Standardization: The collected plasma is a raw material for manufacturing life-saving protein therapies. Consistency and accurate labeling of the product are critical. Knowing the precise volume of pure plasma collected, rather than the volume of a variable mixture, improves process control and product quality. This provides a strong motivation to integrate a pure plasma calculation into the collection system's control loop.

3. Predictable Result: Implementing the calculation from Steele into the controller of a base system like Felt's would have been a matter of routine software programming for a POSITA. It is an application of a known formula to improve the accuracy of a known system. The result—a system that stops based on a calculated pure plasma volume—would have been an entirely predictable improvement.

Therefore, it would have been obvious to modify a standard, weight-based apheresis system to use the donor's hematocrit and the known anticoagulant ratio to calculate the volume of pure plasma in real-time and stop the procedure when that calculated volume reached the prescribed weight-based target. This combination renders the subject matter of Claims 1 and 11 obvious.

Obviousness of Claim 18 (Method)

Claim 18 describes a more advanced method that sets the target collection volume as a percentage of the donor's total calculated plasma volume and subsequently manages the donor's intravascular deficit.

Proposed Combination of Prior Art: The combination for Claims 1 & 11 (e.g., Felt + Steele) further combined with a reference teaching post-donation fluid management (e.g., US 8,951,409 to Smith).

Rationale for Obviousness:

1. Personalized Target Calculation (Elements b, c): The move from a simple weight-based target (as in Claim 1) to a target based on a percentage of the donor's total plasma volume is an obvious step in the evolution of procedure personalization. The physiological formulas to estimate a person's total blood volume and plasma volume from their height, weight, and hematocrit were well-known long before 2017. For a POSITA seeking to create a more physiologically tailored and optimized procedure (a motivation already present in the art), calculating the donor's total plasma pool and targeting a specific fraction of it is a more medically relevant and logical approach than using broad weight brackets. This would be seen as an obvious refinement of the personalization taught in the base references.

2. Fluid Balance Management (Element g): Donor safety and the mitigation of adverse reactions like fainting (vasovagal reactions) due to fluid loss (hypovolemia) are primary concerns in plasmapheresis. The prior art, for example in a reference like Smith, explicitly teaches managing a donor's post-donation intravascular deficit. Smith and similar references teach the benefits of returning a specific volume of saline to the donor to achieve a target fluid balance (e.g., isovolemia, where volume out equals volume in) to reduce such adverse reactions.

Motivation to Combine:

A POSITA who has already developed a system to collect a highly personalized, and potentially larger, volume of pure plasma (as per the Felt+Steele combination) would be immediately confronted with the known problem of donor hypovolemia. It would be an obvious and necessary design step to incorporate a solution for this known problem. Combining the personalized collection method with the fluid-management method taught by Smith would be a combination of known techniques to solve known problems, representing a predictable path to improving overall donor safety and comfort.

Therefore, the method of Claim 18 would have been obvious as it combines:

• A personalized apheresis collection (obvious from Felt + Steele).
• A more refined, physiologically-based targeting method that is an obvious extension of existing personalization trends.
• A known solution (saline return as in Smith) to the known problem of post-donation hypovolemia that arises from the collection itself.